The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of ...approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein‐coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.
To assess outcomes in patients with ILD hospitalized for COVID-19 versus those ...without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.
An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.
Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio HR, 1.60; confidence interval, 1.17-2.18;
= 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).
Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.
The genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution. ...Rates of chromosome evolution within mammalian orders were found to increase since the Cretaceous-Tertiary boundary. Nearly 20% of chromosome breakpoint regions were reused during mammalian evolution; these reuse sites are also enriched for centromeres. Analysis of gene content in and around evolutionary breakpoint regions revealed increased gene density relative to the genome-wide average. We found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement.
Nephronophthisis (NPH) is the most prevalent genetic cause for ESRD in children. However, little is known about the prevalence of NPH in adult-onset ESRD. Homozygous full gene deletions of the
gene ...encoding nephrocystin-1 are a prominent cause of NPH. We determined the prevalence of NPH in adults by assessing homozygous
full gene deletions in adult-onset ESRD.
Adult renal transplant recipients from five cohorts of the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN) underwent single-nucleotide polymorphism genotyping. After quality control, we determined autosomal copy number variants (such as deletions) on the basis of median log2 ratios and B-allele frequency patterns. The findings were independently validated in one cohort. Patients were included in the analysis if they had adult-onset ESRD, defined as start of RRT at ≥18 years old.
We included 5606 patients with adult-onset ESRD; 26 (0.5%) showed homozygous
deletions. No donor controls showed homozygosity for this deletion. Median age at ESRD onset was 30 (range, 18-61) years old for patients with NPH, with 54% of patients age ≥30 years old. Notably, only three (12%) patients were phenotypically classified as having NPH, whereas most patients were defined as having CKD with unknown etiology (
=11; 42%).
Considering that other mutation types in
or mutations in other NPH-causing genes were not analyzed, NPH is a relatively frequent monogenic cause of adult-onset ESRD. Because 88% of patients had not been clinically diagnosed with NPH, wider application of genetic testing in adult-onset ESRD may be warranted.
The Integrated Source Apportionment Method (ISAM) has been revised in the Community Multiscale Air Quality (CMAQ) model. This work updates ISAM to
maximize its flexibility, particularly for ozone ...(O3) modeling, by providing multiple attribution options, including products inheriting
attribution fully from nitrogen oxide reactants, fully from volatile organic compound (VOC) reactants, equally from all reactants, or dynamically from
NOx or VOC reactants based on the indicator gross production ratio of hydrogen peroxide (H2O2) to nitric acid
(HNO3). The updated ISAM has been incorporated into the most recent publicly accessible versions of CMAQ (v5.3.2 and beyond). This study's
primary objective is to document these ISAM updates and demonstrate their impacts on source apportionment results for O3 and its
precursors. Additionally, the ISAM results are compared with the Ozone Source Apportionment Technology (OSAT) in the Comprehensive Air-quality Model
with Extensions (CAMx) and the brute-force method (BF). All comparisons are performed for a 4 km horizontal grid resolution application over
the northeastern US for a selected 2 d summer case study (9 and 10 August 2018). General similarities among ISAM, OSAT, and BF results add
credibility to the new ISAM algorithms. However, some discrepancies in magnitude or relative proportions among tracked sources illustrate the
distinct features of each approach, while others may be related to differences in model formulation of chemical and physical processes. Despite these
differences, OSAT and ISAM still provide useful apportionment data by identifying the geographical and temporal contributions of O3 and
its precursors. Both OSAT and ISAM attribute the majority of O3 and NOx contributions to boundary, mobile, and biogenic
sources, whereas the top three contributors to VOCs are found to be biogenic, boundary, and area sources.
Non-covalent interactions are a ubiquitous mechanism directing assembly of natural materials. Similarly, these types of interactions have become an important component of emerging approaches in ...biomaterials science. In view of the emerging importance of bio-inspired materials in medical applications, this chapter will be focused on describing the fundamentals of intermolecular interactions and their applications in biomaterials science. The particular focus will be on processes and structures that mimic the natural ECM.
An influenza A reassortant virus that contained the hemagglutinin and neuraminidase genes of a virulent human virus, A/Udorn/72 (H3N2), and the six other influenza A virus genome segments from an ...avirulent avian virus, A/Mallard/New York/6750/78 (H2N2), was evaluated for its level of replication in squirrel monkeys and hamsters. In monkeys, the reassortant virus was as attenuated and as restricted in its level of replication in the upper and lower respiratory tract as its avian influenza virus parent. Nonetheless, infection with the reassortant induced significant resistance to challenge with virulent human influenza virus. In hamsters, the reassortant virus replicated to a level intermediate between that of its parents. These findings suggest that the nonsurface antigen genes of the avian parental virus are the primary determinants of restriction of replication of the reassortant virus in monkeys. Attenuation of the reassortant virus for primates is achieved by the inefficient functioning of the avian influenza genes in primate cells, while antigenic specificity of the human influenza virus is provided by the neuraminidase and hemagglutinin genes derived from the human virus. This approach could lead to the development of a live influenza A virus vaccine that is attenuated for man if the avian influenza genes are similarly restricted in human cells.
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