This editorial refers to ‘Relationship among pregnancy associated plasma protein-A levels, clinical characteristics, and coronary artery disease extent in patients with chronic stable angina pectoris’† by J. Cosin-Sales et al., on page 2093 The natural history of coronary artery disease is complex and is characterized by the central role played by inflammation. Atherogenic stimuli, such as oxidized lipoproteins, glycation end products, hypertension, and smoking, cause endothelial dysfunction and apoptosis, vascular expression of adhesion molecules, and recruitment of inflammatory cells, which then migrate in the intima, thus setting the stage for plaque formation.1 Coronary atherosclerotic plaques have a high prevalence in the population, even in subjects dying of non-cardiac causes, and their burden increases with age.2 In many subjects these plaques remain silent for life; in others they suddenly become thrombogenic, triggering occlusive or subocclusive thrombosis, responsible for acute coronary syndromes. In survivors of a first acute coronary event, the latter is followed by a period, lasting about 1 year, of enhanced risk of new acute ischaemic events. Thereafter, the disease enters a new phase of quiescence, which can last for years. In a sizeable proportion of patients, the brisk transition from coronary stability to instability is associated with a sudden and widespread activation of inflammatory cells, detectable in the entire coronary circulation, in the myocardium and, in a subset of patients, even in remote arterial districts.3,4 This inflammatory outburst is not explained by the atherosclerotic burden, by activation of the haemostatic system, or by ischaemia.1 Thus, inflammation appears to play a key part, not only in plaque growth, … *Corresponding author. Tel: +39 06 3051166. E-mail address : filippo.crea{at}rm.unicatt.it
Protein Data Bank (PDB), jointly founded in 1971 by Brookhaven National Laboratory, USA, and the Cambridge Crystallographic Data Centre, UK, is the single global archive of experimentally determined biological macromolecular structures. PDB deposition is mandatory for publication in most scientific journals, which means 'no PDB deposition, no structural publication'. The current PDB archive contains more than 180,000 entries and includes many structures from Asian institutions. The first protein structure from Japan was that of cytochrome c determined by Prof Masao Kakudo's group at the Institute for Protein Research, Osaka University, in 1971 at a resolution of 4 Å, and a subsequent atomic structure at 2.3 Å resolution was deposited to PDB in 1976 as the 1st Asian and 21st entry of the entire PDB archive. Since then, 317 protein structures whose primary citation was the Journal of Biochemistry (J. Biochem.) have been deposited to PDB. Based on this long history between PDB and J. Biochem., a statistical analysis of all structural reports in J. Biochem. has been carried out using the relational database system at PDBj (https://pdbj.org) and reviewed the yearly distribution, resolution, quality of structure, type of target protein, number of citations and comparison against other major journals.
The Publisher regrets that this review article must be withdrawn owing to an issue of multiple publication. The manuscript was submitted in nearly identical form to three journals (Frontiers in Bioscience, Cytokine and Growth Factor Reviews and Journal of Cellular Physiology) and was accepted and published by all three. As the article was accepted and published in Frontiers in Bioscience first, the copyright belongs to that journal. The bibliographic details of the original review article published in Frontiers in Bioscience are: “Caveolins in Cholesterol Trafficking and Signal Transduction: Implications for Human Disease” Amnon Schlegel et al. Frontiers in Bioscience 2000 Dec 1; Volume 5:D929-37 http://www.bioscience.org/2000/v5/d/schlegel/list.htm
Site-selective incorporation of thioamides into peptides and proteins provides a useful tool for a wide range of applications. Current incorporation methods suffer from low yields as well as epimerization. Here, we describe how the use of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) rather than piperidine in fluorenylmethyloxycarbonyl (Fmoc) deprotection reduces epimerization and increases yields of thioamide-containing peptides. Furthermore, we demonstrate that the use of DBU avoids byproduct formation when synthesizing peptides containing side-chain thioamides.
Genes and proteins are often associated with multiple names, and more names are added as new functional or structural information is discovered. Because authors often alternate between these synonyms, information retrieval and extraction benefits from identifying these synonymous names. We have developed a method to extract automatically synonymous gene and protein names from MEDLINE and journal articles. We first identified patterns authors use to list synonymous gene and protein names. We developed SGPE (for synonym extraction of gene and protein names), a software program that recognizes the patterns and extracts from MEDLINE abstracts and full-text journal articles candidate synonymous terms. SGPE then applies a sequence of filters that automatically screen out those terms that are not gene and protein names. We evaluated our method to have an overall precision of 71% on both MEDLINE and journal articles, and 90% precision on the more suitable full-text articles alone
A glycogen synthase kinase was partially purified from rabbit skeletal muscle by precipitation with ammonium sulphate, chromatography on DEAE‐cellulose and chromatography on hydroxyapatite. The enzyme was highly specific for glycogen synthase. In the standard assay, the relative rates of phosphorylation were: glycogen synthase (100), phosvitin (2.5), phosphorylase kinase (< 1), casein (0.3), protein phosphatase inhibitor‐1 (< 0.1), phosphorylase(< 0.01), mixed histones (< 0.01). The enzyme was separated from virtually all phosvitin kinase and casein kinase activity by the chromatography on DEAE‐cellulose. The K m values for ATP and GTP were 0.02 mM and 0.5 mM respectively, and a similar maximum reaction velocity was obtained with each nucleoside triphosphate. The activity of the enzyme was unaffected by cyclic AMP, cyclic GMP, calcium ions, calcium ions plus calmodulin, and the specific protein inhibitor of cyclic‐AMP‐dependent protein kinase. The properties of the enzyme demonstrated that it was distinct from both cyclic‐AMP‐dependent protein kinase and phosphorylase kinase, the two well characterized glycogen synthase kinases in skeletal muscle. This enzyme was therefore termed glycogen synthase kinase‐3. The phosphorylation of glycogen synthase by glycogen synthase kinase‐3 reached a pleateau near 1.5 molecule phosphate incorporated per subunit under optimal conditions. The activity of glycogen synthase measured in the absence of glucose 6‐phosphate was decreased fivefold and the apparent K a for glucose 6‐phosphate was increased 15‐fold, when 1.2 molecule phosphate per sub‐unit had been introduced into the enzyme. Phosphorylation to a similar extent with either cyclic‐AMP‐dependent protein kinase or phosphorylase kinase produced smaller changes in activity. Glycogen synthase was phosphorylated by cyclic‐AMP‐dependent protein kinase, phosphorylase kinase and glycogen synthase kinase‐3, using conditions where the phosphorylation by any one protein kinase reached a plateau near one molecule of phosphate incorporated per subunit. The different protein kinases were used separately and in combination to generate seven different phosphorylated species of glycogen synthase. The phosphorylation of glycogen synthase approached two molecules per subunit when any two protein kinases were combined, and three molecules per subunit when all three protein kinases were combined, and the inactivation produced by the different protein kinases was essentially additive. The results imply that each protein kinase preferentially phosphorylates a different site(s) on glycogen synthase, and this is confirmed by the amino acid sequence analysis described in the following paper in this journal.
This article is an introduction to the special issue of the journal PROTEINS, dedicated to the tenth Critical Assessment of Structure Prediction (CASP) experiment to assess the state of the art in protein structure modeling. The article describes the conduct of the experiment, the categories of prediction included, and outlines the evaluation and assessment procedures. The 10 CASP experiments span almost 20 years of progress in the field of protein structure modeling, and there have been enormous advances in methods and model accuracy in that period. Notable in this round is the first sustained improvement of models with refinement methods, using molecular dynamics. For the first time, we tested the ability of modeling methods to make use of sparse experimental three-dimensional contact information, such as may be obtained from new experimental techniques, with encouraging results. On the other hand, new contact prediction methods, though holding considerable promise, have yet to make an impact in CASP testing. The nature of CASP targets has been changing in recent CASPs, reflecting shifts in experimental structural biology, with more irregular structures, more multi-domain and multi-subunit structures, and less standard versions of known folds. When allowance is made for these factors, we continue to see steady progress in the overall accuracy of models, particularly resulting from improvement of non-template regions.
A matching algorithm using surface complementarity between receptor and ligand protein molecules is outlined. The molecular surfaces are represented by "critical points," describing holes and knobs. Holes (maxima of a shape function) are matched with knobs (minima). This simple and appealing surface representation has been previously described by Connolly [(1986) Biopolymers, Vol. 25, pp. 1229-1247]. However, attempts to implement this description in a docking scheme have been unsuccessful (e.g., Connolly, ibid.). In order to decrease the combinatorial complexity, and to make the execution time affordable, four critical hole/knob point matches were sought. This approach failed since some bound interfaces are relatively flat and do not possess four critical point matches. On the otherhand, matchings of fewer critical points require a very time-consuming, full conformational (grid) space search [Wang, (1991) Journal of Computational Chemistry, Vol. 12, pp. 746-750]. Here we show that despite the initial failure of this approach, with a simple and straightforward modification in the matching algorithm, this surface representation works well. Out of the 16 protein-protein complexes we have tried, 15 were successfully docked, including two immunoglobulins. The entire molecular surfaces were considered, with absolutely no additional information regarding the binding sites. The whole process is completely automated, with no manual intervention, either in the input atomic coordinate data, or in the matching. We have been able to reach this level of performance with the hole/knob surface description by using pairs of critical points along with their surface normals in the calculation of the transformation matrix. The success of this approach suggests that future docking methods should use geometric docking as the first screening filter.(ABSTRACT TRUNCATED AT 250 WORDS)
HYPOPHYSECTOMIZED rats have a defect in the synthesis of matrix protein which is rapidly repaired by the administration of GH in vivo. In 1957, it was first reported that this defect, as determined by measuring the incorporation of [35S]sulfate into chondroitin sulfate, could not be corrected by addition of GH to media containing cartilage segments (1). The defect, however, was rapidly corrected by the addition of diluted normal rat serum to such media, but serum from hypophysectomized rats was virtually inactive. It was proposed that GH acted on skeletal tissues by inducing the formation of a direct acting intermediary growth factor. This hypothesis, commonly referred to as the somatomedin hypothesis, has been extensively confirmed and recently extended to include autocrine and paracrine roles of somatomedins in many tissues as well as the originally recognized endocrine role of this growth factor. Research in the somatomedins has increased so much in recent years that a comprehensive review of the subject is no longer possible within the length constraints of this Journal. In this review, we will focus on the insulin-like growth factors (IGFs) that are present in body fluids and tissues. We will review the rapidly developing information about the molecular biology of the biosynthesis of IGFs and their regulation in fetal and postnatal life and the possible role of IGF biosynthesis in tissue repair and hypertrophy. Last, we will consider the relative contribution of endocrine as opposed to autocrine/paracrine actions of IGF-I in skeletal growth. Not included in this review will be a consideration of IGF binding proteins, IGF receptors, and postbinding effector mechanisms. Readers are referred to recent reviews for consideration of these topics (2–4).
The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank(®) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. Additional NCBI resources focus on literature (PubMed Central (PMC), Bookshelf and PubReader), health (ClinVar, dbGaP, dbMHC, the Genetic Testing Registry, HIV-1/Human Protein Interaction Database and MedGen), genomes (BioProject, Assembly, Genome, BioSample, dbSNP, dbVar, Epigenomics, the Map Viewer, Nucleotide, Probe, RefSeq, Sequence Read Archive, the Taxonomy Browser and the Trace Archive), genes (Gene, Gene Expression Omnibus (GEO), HomoloGene, PopSet and UniGene), proteins (Protein, the Conserved Domain Database (CDD), COBALT, Conserved Domain Architecture Retrieval Tool (CDART), the Molecular Modeling Database (MMDB) and Protein Clusters) and chemicals (Biosystems and the PubChem suite of small molecule databases). The Entrez system provides search and retrieval operations for most of these databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
The ability to take up and metabolize glucose at the cellular level is a property shared by the vast majority of existing organisms. Most mammalian cells import glucose by a process of facilitative diffusion mediated by members of the Glut (SLC2A) family of membrane transport proteins. Fourteen Glut proteins are expressed in the human and they include transporters for substrates other than glucose, including fructose, myoinositol, and urate. The primary physiological substrates for at least half of the 14 Glut proteins are either uncertain or unknown. The well-established glucose transporter isoforms, Gluts 1-4, are known to have distinct regulatory and/or kinetic properties that reflect their specific roles in cellular and whole body glucose homeostasis. Separate review articles on many of the Glut proteins have recently appeared in this journal. Here, we provide a very brief summary of the known properties of the 14 Glut proteins and suggest some avenues of future investigation in this area.
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, http://www.guidetopharmacology.org) provides expert-curated molecular interactions between successful and potential drugs and their targets in the human genome. Developed by the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS), this resource, and its earlier incarnation as IUPHAR-DB, is described in our 2014 publication. This update incorporates changes over the intervening seven database releases. The unique model of content capture is based on established and new target class subcommittees collaborating with in-house curators. Most information comes from journal articles, but we now also index kinase cross-screening panels. Targets are specified by UniProtKB IDs. Small molecules are defined by PubChem Compound Identifiers (CIDs); ligand capture also includes peptides and clinical antibodies. We have extended the capture of ligands and targets linked via published quantitative binding data (e.g. Ki, IC50 or Kd). The resulting pharmacological relationship network now defines a data-supported druggable genome encompassing 7% of human proteins. The database also provides an expanded substrate for the biennially published compendium, the Concise Guide to PHARMACOLOGY. This article covers content increase, entity analysis, revised curation strategies, new website features and expanded download options.
InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.
Indexed:American Chemical Society's Chemical Abstracts Service (CAS)PubMed (files to appear soon)MedLineScience Citation Expanded (also known as SciSearch®Current Contents®/Clinical MedicineJournal Citation Reports/Science EditionISSN 1176-9114 (Print)ISSN 1178-2013 (Online)An international, peer-reviewed journal focusing on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Reflecting the growing activity in this emerging specialty, the aim of this journal is to highlight research and development leading to potential clinical applications in the prevention and treatment of disease.Key benefitsConcise rapid reportingFocus on basic science, engineering, and nanotechnologyExisting and potential clinical applicationsInternational scopeAn international, peer-reviewed journal of basic science, engineering, diagnostics, and pharmaceutical and clinical development focusing on concise rapid reporting of original research and reviews in nanomedicine. Special attention will be given to papers reporting on actual or potential clinical applications leading to improved prevention or treatment of disease or a greater understanding of pathological processes.Subject areas include:Application of nanotechnology in the diagnosis, prevention, and treatment of disease Diagnostic tools, analytical techniques, including biochips, microarrays, biosensors, molecular sensors, nanoprobes, nanoscale genomic and proteomic research, and nanoimaging Nanodevices and nanomaterials, including nanotubes, fullerenes, biomedical microsystems, device miniaturization, cellular and tissue engineering, nano bioresponsive systems (diagnostic and drug delivery devices), and medical nanorobotics Nanodrug complexes and drug delivery systems including polymer therapeutics (eg, pegylated proteins, polymer drug conjugates, polymeric drugs) for improved drug, protein, or gene transport and targeting Specific focus on development and clinical use from the perspectives of safety, efficacy, economics, and ultimate patient uptake. These areas are addressed through:Original research (full papers and concise rapid reports) Reviews Systematic reviews of individual agents, systems or devices Letters to the editor Expert opinion and commentary.
BACKGROUND: Jasmonates are important regulators in plant responses to biotic and abiotic stresses as well as in development. Synthesized from lipid-constituents, the initially formed jasmonic acid is converted to different metabolites including the conjugate with isoleucine. Important new components of jasmonate signalling including its receptor were identified, providing deeper insight into the role of jasmonate signalling pathways in stress responses and development. SCOPE: The present review is an update of the review on jasmonates published in this journal in 2007. New data of the last five years are described with emphasis on metabolites of jasmonates, on jasmonate perception and signalling, on cross-talk to other plant hormones and on jasmonate signalling in response to herbivores and pathogens, in symbiotic interactions, in flower development, in root growth and in light perception. CONCLUSIONS: The last few years have seen breakthroughs in the identification of JASMONATE ZIM DOMAIN (JAZ) proteins and their interactors such as transcription factors and co-repressors, and the crystallization of the jasmonate receptor as well as of the enzyme conjugating jasmonate to amino acids. Now, the complex nature of networks of jasmonate signalling in stress responses and development including hormone cross-talk can be addressed.
The Pfam database is a widely used resource for classifying protein sequences into families and domains. Since Pfam was last described in this journal, over 350 new families have been added in Pfam 33.1 and numerous improvements have been made to existing entries. To facilitate research on COVID-19, we have revised the Pfam entries that cover the SARS-CoV-2 proteome, and built new entries for regions that were not covered by Pfam. We have reintroduced Pfam-B which provides an automatically generated supplement to Pfam and contains 136 730 novel clusters of sequences that are not yet matched by a Pfam family. The new Pfam-B is based on a clustering by the MMseqs2 software. We have compared all of the regions in the RepeatsDB to those in Pfam and have started to use the results to build and refine Pfam repeat families. Pfam is freely available for browsing and download at http://pfam.xfam.org/.
ABSTRACT Marine mussels secret protein‐based adhesives, which enable them to anchor to various surfaces in a saline, intertidal zone. Mussel foot proteins (Mfps) contain a large abundance of a unique, catecholic amino acid, Dopa, in their protein sequences. Catechol offers robust and durable adhesion to various substrate surfaces and contributes to the curing of the adhesive plaques. In this article, we review the unique features and the key functionalities of Mfps, catechol chemistry, and strategies for preparing catechol‐functionalized polymers. Specifically, we reviewed recent findings on the contributions of various features of Mfps on interfacial binding, which include coacervate formation, surface drying properties, control of the oxidation state of catechol, among other features. We also summarized recent developments in designing advanced biomimetic materials including coacervate‐forming adhesives, mechanically improved nano‐ and micro‐composite adhesive hydrogels, as well as smart and self‐healing materials. Finally, we review the applications of catechol‐functionalized materials for the use as biomedical adhesives, therapeutic applications, and antifouling coatings. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55 , 9–33
There is extensive interest in automating the collection, organization and analysis of biological data. Data in the form of images present special challenges for such efforts. Since fluorescence microscope images are a primary source of information about the location of proteins within cells, we have set as a long-term goal the building of a knowledge base system that can interpret such images in online journals. To this end, we first developed a robot that searches online journals and finds fluorescence microscope images of individual cells. We then characterized the applicability of pattern classification methods we have previously used on images obtained under controlled conditions to images from different sources and to images subjected to manipulations commonly performed during publication. The results indicate the feasibility of developing search engines to find fluorescence microscope images depicting particular subcellular patterns.
The USDA this week confirmed the first known infection of the carnivorous fly larva, which feast on the flesh of living mammals, after the United States eradicated the nightmare bugs in the 1960s
Aluminum (Al) toxicity in acid soils is a significant limitation to crop production worldwide, as approximately 50% of the world's potentially arable soil is acidic. Because acid soils are such an important constraint to agriculture, understanding the mechanisms and genes conferring resistance to Al toxicity has been a focus of intense research interest in the decade since the last article on crop acid soil tolerance was published in this journal. An impressive amount of progress has been made during that time that has greatly increased our understanding of the diversity of Al resistance genes and mechanisms, how resistance gene expression is regulated and triggered by Al and Al-induced signals, and how the proteins encoded by these genes function and are regulated. This review examines the state of our understanding of the physiological, genetic, and molecular bases for crop Al tolerance, looking at the novel Al resistance genes and mechanisms that have been identified over the past ten years. Additionally, it examines how the integration of molecular and genetic analyses of crop Al resistance is starting to be exploited for the improvement of crop plants grown on acid soils via both molecular-assisted breeding and biotechnology approaches.