IUPHAR-DB: An Expert-Curated, Peer-Reviewed Database of Receptors and Ion Channels

The International Union of Basic and Clinical Pharmacology database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of about a third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. Individual gene pages provide a comprehensive description of the genes and their functions, with information on protein structure, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). The phenotypes resulting from altered gene expression (e.g. in genetically altered animals) and genetic mutations are described. Links are provided to bioinformatics resources such as NCBI RefSeq, OMIM, PubChem, human, rat and mouse genome databases. Recent developments include the addition of ligand-centered pages summarising information about unique ligand molecules in IUPHAR-DB. IUPHAR-DB represents a novel approach to biocuration because most data are provided through manual curation of published literature by a network of over 60 expert subcommittees coordinated by NC-IUPHAR. Data are referenced to the primary literature and linked to PubMed. The data are checked to ensure accuracy and consistency by the curators, added to the production server using custom-built submission tools and peer-reviewed by NC-IUPHAR, before being transferred to the public database. Data are reviewed and updated regularly (at least biennially). Other website features include comprehensive database search tools, online and downloadable gene lists and links to recent publications of interest to the field, such as reports on receptor-ligand pairings. The database is freely available at "http://www.iuphar-db.org":http://www.iuphar-db.org. Curators can be reached at curators [at] iuphar-db.org. We thank British Pharmacological Society, UNESCO (through the ICSU Grants Programme), Incyte, GlaxoSmithKline, Novartis, Servier and Wyeth for their support

NEMA NU 2-2018 performance evaluation of a new generation 30-cm axial field-of-view Discovery MI PET/CT.

PURPOSE The DMI PET/CT is a modular silicon photomultiplier-based scanner with an axial field-of-view (FOV) between 15 and 25 cm depending on ring configuration (3, 4, or 5 rings). A new generation of the system includes a reengineered detector module, featuring improved electronics and an additional 6th ring, extending the axial FOV to 30 cm. We report on the performance evaluation of the 6-ring upgraded Generation 2 (Gen2) system while values are also reported for the 5-ring configuration of the very same system prior to the upgrade. METHODS PET performance was evaluated using the NEMA NU 2-2018 standard for spatial resolution, sensitivity, image quality, count rate performance, timing resolution, and image co-registration accuracy. Patient images were used to assess image quality. RESULTS The average system sensitivity was measured at 32.76 cps/kBq (~ 47% increase to 5 rings at 22.29 cps/kBq) while noise equivalent count rate peaked at 434.3 kcps corresponding to 23.6 kBq/mL (~ 60% increase to Generation 1 (Gen1) and 39% to Gen2 5 rings). Contrast recovery ranged between 54.5 and 85.8% similar to 5 rings, while the 6 rings provided lower background variability (2.3-8.5% for 5 rings vs 1.9-6.8% for 6 rings) and lower lung error (4.0% for the 5 rings and 3.16% for the 6 rings). Transverse/axial full width at half-maximum (FWHM) at 1 cm (3.79/4.26 mm) and 10 cm (4.29/4.55 mm), scatter fraction (40.2%), energy resolution (9.63%), and time-of-flight (TOF) resolution (389.6 ps at 0 kBq/mL) were in line to previously reported values measured across different system configurations. Improved patient image quality is obtained with the 6 rings compared to the 5 rings, while image quality is retained even at reduced scan times, enabling WB dynamic acquisitions. CONCLUSIONS The higher sensitivity of the 6-ring DMI compared to the 5-ring configuration may lead to improved image quality of clinical images at reduced scan time. Additionally, it could equally be used to allow improved temporal sampling and/or reduced overall scan time in dynamic acquisitions. Conversely, temporal sampling and scan time could be traded per application to further drive injected dose at lower levels

Murine glial progenitor cells transplantation and synthetic PreImplantation Factor (sPIF) reduces inflammation and early motor impairment in ALS mice.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuronal disorder characterized by neuronal degeneration and currently no effective cure is available to stop or delay the disease from progression. Transplantation of murine glial-restricted precursors (mGRPs) is an attractive strategy to modulate ALS development and advancements such as the use of immune modulators could potentially extend graft survival and function. Using a well-established ALS transgenic mouse model (SOD1G93A), we tested mGRPs in combination with the immune modulators synthetic PreImplantation Factor (sPIF), Tacrolimus (Tac), and Costimulatory Blockade (CB). We report that transplantation of mGRPs into the cisterna magna did not result in increased mice survival. The addition of immunomodulatory regimes again did not increase mice lifespan but improved motor functions and sPIF was superior compared to other immune modulators. Immune modulators did not affect mGRPs engraftment significantly but reduced pro-inflammatory cytokine production. Finally, sPIF and CB reduced the number of microglial cells and prevented neuronal number loss. Given the safety profile and a neuroprotective potential of sPIF, we envision its clinical application in near future

The potential consequences for cell Signaling by a class of NOD-Like Receptor proteins (NLRs) bearing an N-terminal signal sequence

The authors gratefully acknowledge the support of the UK Biotechnology and Biological Sciences Research Council (BBSRC) for the work on cellular 2A-like sequences.Publisher PDFPeer reviewe

Fortification and health: challenges and opportunities.

Fortification is the process of adding nutrients or non-nutrient bioactive components to edible products (e.g., food, food constituents, or supplements). Fortification can be used to correct or prevent widespread nutrient intake shortfalls and associated deficiencies, to balance the total nutrient profile of a diet, to restore nutrients lost in processing, or to appeal to consumers looking to supplement their diet. Food fortification could be considered as a public health strategy to enhance nutrient intakes of a population. Over the past century, fortification has been effective at reducing the risk of nutrient deficiency diseases such as beriberi, goiter, pellagra, and rickets. However, the world today is very different from when fortification emerged in the 1920s. Although early fortification programs were designed to eliminate deficiency diseases, current fortification programs are based on low dietary intakes rather than a diagnosable condition. Moving forward, we must be diligent in our approach to achieving effective and responsible fortification practices and policies, including responsible marketing of fortified products. Fortification must be applied prudently, its effects monitored diligently, and the public informed effectively about its benefits through consumer education efforts. Clear lines of authority for establishing fortification guidelines should be developed and should take into account changing population demographics, changes in the food supply, and advances in technology. This article is a summary of a symposium presented at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 on current issues involving fortification focusing primarily on the United States and Canada and recommendations for the development of responsible fortification practices to ensure their safety and effectiveness

Neurophysiological indices of the effect of cognates on vowel perception in late Spanish-English bilinguals

It is well established that acquiring a second language (L2) later in life results in less accurate production and perception of speech sounds in the L2. Languages like Spanish and English have many common words (cognates) and similar sounds, learning how the combination of cognate status and sound similarity can affect processing and lexical access in an L2 is of interest to educators. In the present study, fifteen monolingual English-speakers and 15 late Spanish-English bilinguals were presented with Spanish-English cognates and non-cognates. Event related potentials (ERP) were used to determine whether late L2-learners had more difficulty discriminating mispronunciations of vowels in English words that have Spanish cognates compared to words that do not have cognates. Behavioral results indicated effects of language background differences, but not cognate status, on participants’ ability to discriminate mispronunciations of English vowels, with bilinguals showing poorer discrimination. ERP results revealed that cognate words facilitated L2 phonological processing as evidenced by a larger frontal positive component (P400) ERP effect, similar in amplitude to the P400 from monolinguals. Results suggest that cognate words facilitate not only vocabulary acquisition, but also speech processing, in adult L2 learners, and, thus, may also be useful as a tool for perceptual learning