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https://www.readbyqxmd.com/read/28796998/microrna-dependent-control-of-serotonin-induced-pulmonary-arterial-contraction
#1
Diana Dahan, Tran Thi Hien, Philip Tannenberg, Mari Ekman, Catarina Rippe, Thomas Boettger, Thomas Braun, Karin Tran-Lundmark, Phan-Kiet Tran, Karl Swärd, Sebastian Albinsson
BACKGROUND: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. METHODS: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. RESULTS: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced...
August 11, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28715095/a-self-sacrificing-n-methyltransferase-is-the-precursor-of-the-fungal-natural-product-omphalotin
#2
Sascha Ramm, Bartlomiej Krawczyk, Agnes Mühlenweg, Annette Poch, Eva Mösker, Roderich D Süssmuth
Research on ribosomally synthesized and posttranslationally modified peptides (RiPPs) has led to an increasing understanding of biosynthetic mechanisms, mostly drawn from bacterial examples. In contrast, reports on RiPPs from fungal producers, apart from the amanitins and phalloidins, are still scarce. The fungal cyclopeptide omphalotin A carries multiple N-methylations on the peptide backbone, a modification previously known only from nonribosomal peptides. Mining the genome of the omphalotin-producing fungus for a precursor peptide led to the identification of two biosynthesis genes, one encoding a methyltransferase OphMA that catalyzes the automethylation of its C-terminus, which is then released and cyclized by the protease OphP...
July 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28704043/structural-insights-into-thioether-bond-formation-in-the-biosynthesis-of-sactipeptides
#3
Tyler L Grove, Paul Michael Himes, Sungwon Hwang, Hayretin Yumerefendi, Jeffrey B Bonanno, Brian Kuhlman, Steven C Almo, Albert A Bowers
Sactipeptides are ribsomally-produced peptides that contain a characteristic thioether bridge (sactionine bond) that is installed posttranslationally and is absolutely required for their antibiotic activity. Sactipeptide biosynthesis requires a unique class of radical SAM enzymes that contain multiple [4Fe-4S] clusters to form the requisite thioether bridge between a cysteine and the α-carbon of an opposing amino acid through radical chemistry. Here we present the structure of the sactionine bond forming enzyme CteB, from Clostridium thermocellum ATCC 27405, with both SAM and an N-terminal fragment of it's peptidyl-substrate at 2...
July 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28691075/chimeric-leader-peptides-for-the-generation-of-non-natural-hybrid-ripp-products
#4
Brandon J Burkhart, Nidhi Kakkar, Graham A Hudson, Wilfred A van der Donk, Douglas A Mitchell
Combining biosynthetic enzymes from multiple pathways is an attractive approach for producing molecules with desired structural features; however, progress has been hampered by the incompatibility of enzymes from unrelated pathways and intolerance toward alternative substrates. Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a diverse natural product class that employs a biosynthetic logic that is highly amenable to engineering new compounds. RiPP biosynthetic proteins modify their substrates by binding to a motif typically located in the N-terminal leader region of the precursor peptide...
June 28, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28682627/ribosomal-natural-products-tailored-to-fit
#5
Michael A Funk, Wilfred A van der Donk
Ribosomally synthesized and Post-translationally modified Peptides (RiPPs) take advantage of the ribosomal translation machinery to generate linear peptides that are subsequently modified with heterocycles and/or macrocycles to impose three-dimensional structure and thwart degradation by proteases. Although RiPP precursors are limited to proteinogenic amino acids, post-translational modifications (PTMs) can alter the structure of individual amino acids and thereby improve the stability and biological activity of the molecule...
July 18, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28678974/clinical-performance-and-failure-modes-of-pulpless-teeth-restored-with-posts-a-systematic-review
#6
Ana Maria Estivalete Marchionatti, Vinícius Felipe Wandscher, Marília Pivetta Rippe, Osvaldo Bazzan Kaizer, Luiz Felipe Valandro
The aim of this systematic review was to compare the clinical performance and failure modes of teeth restored with intra-radicular retainers. A search was performed on PubMed/Medline, Central and ClinicalTrials databases for randomized clinical trials comparing clinical behavior and failures of at least two types of retainers. From 341 detected papers, 16 were selected for full-text analysis, of which 9 met the eligibility criteria. A manual search added 2 more studies, totalizing 11 studies that were included in this review...
July 3, 2017: Brazilian Oral Research
https://www.readbyqxmd.com/read/28650175/bioactive-peptide-natural-products-as-lead-structures-for-medicinal-use
#7
Tam Dang, Roderich D Süssmuth
The need for new drugs for the treatment of various diseases is enormous. From the previous century until the present, numerous peptide and peptide-derived natural products have been isolated from bacteria and fungi. Hence, microorganisms play a pivotal role as sources for novel drugs with an emphasis on anti-infective agents. Various disciplines from biology, chemistry, and medicine are involved in early stages of the search for peptide natural products including taxonomy, microbiology, bioanalytics, bioinformatics, and medicinal chemistry...
June 26, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28634235/mechanistic-elucidation-of-the-mycofactocin-biosynthetic-radical-s-adenosylmethionine-protein-mftc
#8
Bulat Khaliullin, Richard Ayikpoe, Mason Tuttle, John A Latham
Ribosomally synthesized and posttranslationally modified peptide (RiPP) pathways produce a diverse array of natural products. A subset of these pathways depends on radical S-adenosylmethionine proteins to modify the RiPP-produced peptide. Mycofactocin biosynthesis is one example of an S-adenosylmethionine protein-dependent RiPP pathway. Recently, it has been shown that MftC catalyzes the oxidative decarboxylation of the C-terminal tyrosine (Tyr-30) on the mycofactocin precursor peptide MftA; however, this product has not been verified by techniques other than MS...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28623182/mygenefriends-a-social-network-linking-genes-genetic-diseases-and-researchers
#9
Alexis Allot, Kirsley Chennen, Yannis Nevers, Laetitia Poidevin, Arnaud Kress, Raymond Ripp, Julie Dawn Thompson, Olivier Poch, Odile Lecompte
BACKGROUND: The constant and massive increase of biological data offers unprecedented opportunities to decipher the function and evolution of genes and their roles in human diseases. However, the multiplicity of sources and flow of data mean that efficient access to useful information and knowledge production has become a major challenge. This challenge can be addressed by taking inspiration from Web 2.0 and particularly social networks, which are at the forefront of big data exploration and human-data interaction...
June 16, 2017: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/28608363/misynpat-an-integrated-knowledge-base-linking-clinical-genetic-and-structural-data-for-disease-causing-mutations-in-human-mitochondrial-aminoacyl-trna-synthetases
#10
Luc Moulinier, Raymond Ripp, Gaston Castillo, Olivier Poch, Marie Sissler
Numerous mutations in each of the mitochondrial aminoacyl-tRNA synthetases have been implicated in human diseases. The mutations are autosomal and recessive and lead mainly to neurological disorders, although with pleiotropic effects. The processes and interactions that drive the etiology of the disorders associated with mitochondrial aminoacyl-tRNA synthetases are far from understood. The complexity of the clinical, genetic and structural data requires concerted, interdisciplinary efforts to understand the molecular biology of these disorders...
June 12, 2017: Human Mutation
https://www.readbyqxmd.com/read/28606854/divergent-roles-of-the-drosophila-melanogaster-globins
#11
Thorsten Burmester, Agnes Wawrowski, Ines Diepenbruck, Katharina Schrick, Nina Seiwert, Fabian Ripp, Andreas Prothmann, Thomas Hankeln
In contrast to long-held assumptions, the gene repertoire of most insects includes hemoglobins. Analyses of the genome of the fruitfly Drosophila melanogaster identified three distinct hemoglobin genes (glob1, glob2, and glob3). While glob1 is predominantly associated with the tracheal system and fat body, glob2 and glob3 are almost exclusively expressed in the testis. The physiological role of globins in Drosophila is uncertain. Here, we studied the functions of the three globins in a cell culture system. Drosophila Schneider 2 (S2) cells were stably transfected with each of the three globins and the empty vector as control...
June 9, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28604729/dnmt-and-hdac-inhibitors-induce-cryptic-transcription-start-sites-encoded-in-long-terminal-repeats
#12
David Brocks, Christopher R Schmidt, Michael Daskalakis, Hyo Sik Jang, Nakul M Shah, Daofeng Li, Jing Li, Bo Zhang, Yiran Hou, Sara Laudato, Daniel B Lipka, Johanna Schott, Holger Bierhoff, Yassen Assenov, Monika Helf, Alzbeta Ressnerova, Md Saiful Islam, Anders M Lindroth, Simon Haas, Marieke Essers, Charles D Imbusch, Benedikt Brors, Ina Oehme, Olaf Witt, Michael Lübbert, Jan-Philipp Mallm, Karsten Rippe, Rainer Will, Dieter Weichenhan, Georg Stoecklin, Clarissa Gerhäuser, Christopher C Oakes, Ting Wang, Christoph Plass
Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions...
July 2017: Nature Genetics
https://www.readbyqxmd.com/read/28591521/changes-in-face-specific-neural-processing-explain-reduced-cuteness-and-approachability-of-infants-with-cleft-lip
#13
Renske Huffmeijer, Janna Eilander, Viara R Mileva-Seitz, Ralph C A Rippe
The current study investigated whether changes in the neural processing of faces of infants with a facial abnormality - a cleft lip - mediate effects of the cleft lip on judgments of infant cuteness and approachability. Event-related potentials (ERPs) in response to pictures of faces of healthy infants and infants with a cleft lip, and ratings of cuteness and approachability of these infant faces, were obtained from 30 females. Infants with a cleft lip were rated as less attractive (less cute and approachable) than healthy infants, and both the N170 and P2 components of the ERP were of reduced amplitude in response to pictures of infants with a cleft lip...
June 18, 2017: Social Neuroscience
https://www.readbyqxmd.com/read/28584123/characterization-of-the-macrocyclase-involved-in-the-biosynthesis-of-ripp-cyclic-peptides-in-plants
#14
Jonathan R Chekan, Paola Estrada, Patrick S Covello, Satish K Nair
Enzymes that can catalyze the macrocyclization of linear peptide substrates have long been sought for the production of libraries of structurally diverse scaffolds via combinatorial gene assembly as well as to afford rapid in vivo screening methods. Orbitides are plant ribosomally synthesized and posttranslationally modified peptides (RiPPs) of various sizes and topologies, several of which are shown to be biologically active. The diversity in size and sequence of orbitides suggests that the corresponding macrocyclases may be ideal catalysts for production of cyclic peptides...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28576760/mathermycin-a-lantibiotic-from-the-marine-actinomycete-marinactinospora-thermotolerans-scsio-00652
#15
Erquan Chen, Qi Chen, Shaoming Chen, Bing Xu, Jianhua Ju, Huan Wang
Lantibiotics are antimicrobial peptides belonging to the family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and feature thioether linkages in their structures. In this study, we identified the biosynthetic gene cluster of a cinnamycin analog, named mathermycin, from Marinactinospora thermotolerans SCSIO 00652 and reconstituted its biosynthesis in Streptomyces lividans and Escherichia coli Key posttranslational modification enzymes of mathermycin were characterized. Mathermycin exhibited antimicrobial activity and therefore represents an example of cinnamycin-like lantibiotics from Marinactinospora species...
August 1, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28544148/structure-and-biosynthesis-of-crocagins-polycyclic-postranslationally-modified-ribosomal-peptides-from-chondromyces-crocatus
#16
Konrad Viehrig, Frank Surup, Carsten Volz, Jennifer Herrmann, Antoine Abou Fayad, Sebastian Adam, Jesko Köhnke, Dirk Trauner, Rolf Müller
Secondary metabolome mining efforts in the myxobacterial multiproducer of natural products, Chondromyces crocatus Cm c5, resulted in the isolation and structure elucidation of crocagins, which are novel polycyclic peptides containing a tetrahydropyrrolo[2,3-b]indole core. The gene cluster was identified through an approach combining genome analysis, targeted gene inactivation in the producer, and in vitro experiments. Based on our findings, we developed a biosynthetic scheme for crocagin biosynthesis. These natural products are formed from the three C-terminal amino acids of a precursor peptide and thus belong to a novel class of ribosomally synthesized and post-translationally modified peptides (RiPPs)...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28542204/similar-regulatory-mechanisms-of-caveolins-and-cavins-by-myocardin-family-coactivators-in-arterial-and-bladder-smooth-muscle
#17
Baoyi Zhu, Catarina Rippe, Tran Thi Hien, Jianwen Zeng, Sebastian Albinsson, Karin G Stenkula, Bengt Uvelius, Karl Swärd
Caveolae are membrane invaginations present at high densities in muscle and fat. Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences...
2017: PloS One
https://www.readbyqxmd.com/read/28535034/p450-mediated-non-natural-cyclopropanation-of-dehydroalanine-containing-thiopeptides
#18
Joshua G Gober, Swapnil V Ghodge, Jonathan W Bogart, Walter J Wever, Richard R Watkins, Eric M Brustad, Albert A Bowers
Thiopeptides are a growing class of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products. Many biosynthetic enzymes for RiPPs, especially thiopeptides, are promiscuous and can accept a wide range of peptide substrates with different amino acid sequences; thus, these enzymes have been used as tools to generate new natural product derivatives. Here, we explore an alternative route to molecular complexity by engineering thiopeptide tailoring enzymes to do new or non-native chemistry...
June 1, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28507018/erratum-for-rippe-and-angelopoulos-fructose-containing-sugars-and-cardiovascular-disease-adv-nutr-2015-6-430-9
#19
(no author information available yet)
No abstract text is available yet for this article.
May 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28507017/erratum-for-rippe-the-metabolic-and-endocrine-response-and-health-implications-of-consuming-sugar-sweetened-beverages-findings-from-recent-randomized-controlled-trials-adv-nutr-2013-4-677-86
#20
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