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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 over 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/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, 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 immunization of mice with the sterile culture medium supernatants of Mycobacterium tuberculosis (Mtb) H37Rv permitted the production of several monoclonal antibodies (mAbs) specific for secreted and/or released antigens. Two mAbs bound and immunoprecipitated an 80-kDa protein that was identified by mass spectrometry as Rv1133c, the methionine synthase MetE. The protein MetE is ubiquitous among prokaryota and shows a significant sequence homology in many bacteria. We produced both the full-length recombinant MetE and its N-terminal fragment, whose sequence is more conserved among mycobacteria, to select mAbs recognizing an Mtb-specific region of MetE. Finally, we produced and selected eight mAbs that specifically detect the MetE protein in the supernatant and cell lysate of Mtb and BCG, but not other bacteria such as non-tuberculous mycobacteria (NTM), Streptococcus pneumoniae, Staphylococcus aureus, Acinetobacter baumanii, or Escherichia coli. Taking advantage of our mAbs, we studied (i) the vitamin B12 dependence for the synthesis of MetE in Mtb and NTM and (ii) the kinetics of MetE production and secretion in supernatants during the in vitro reproduced replicative, dormant, and resuscitation cycle of Mtb. Our data demonstrate that dormant Mtb, which are assumed to be prevalent in latent infections, as well as NTM do not produce and secrete MetE. Results indicate an unexpected specificity for Mtb of our anti-MetE mAbs and encourage the use of rMetE and our mAbs as tools for the immunodiagnosis of TB and its stages.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

El presente artículo busca contribuir al desarrollo y consolidación de los estudios sobre la gourmetización y la gentrificación alimentaria, enfatizando los efectos que estos procesos tienen en ámbitos que exceden a la vida urbana. En ese marco, se propone recuperar los engranajes de la cadena de valor y sus localizaciones –desde los barrios gentrificados hasta las comunidades rurales agrícolas–, indicando los procesos de valorización y desvalorización y cómo estos afectan de forma desigual a los actores involucrados. Se enfatiza sobre este punto, estableciendo un diálogo interdisciplinar. A partir de una revisión bibliográfica, el artículo se basa en cuatro casos que se recuperan de fuentes secundarias y que ilustran la forma en la que operan estos procesos en distintos niveles, territorios y escalas: el café de autor en cuanto símbolo de distinción en los barrios gentrificados; la palta o aguacate a partir de su manifestación gastronómica en el avocado toast; el vino, desde la turistificación de su producción hasta las estrategias de valorización en su consumo urbano; y la quinoa desde el patentamiento de nuevas variedades hasta el desarrollo de mercados expulsivos de amplios sectores de población. Se concluye que el auge de estos alimentos tiene efectos de acumulación del capital por desposesión en los ámbitos rural y urbano al igual que en los procesos de producción y de consumo.

The research for non-fluorinated polymeric electrolytes able to operate at temperatures of 80–120 °C, the so-called “conductivity gap”, is becoming central. Within this frame, the present work discusses the investigation of innovative self-assembling polybenzimidazole/sulfonated graphene oxide (PBI/SGO) composite membranes. A set of five samples, characterized by never-explored PBI-to-SGO mass ratios between 3:1 and 1:3, is studied through surface and cross-sectional SEM, XRD, ATR-FTIR spectroscopy, and TGA. The experimental outcomes reveal the reciprocal compatibility between PBI and SGO, whose main features appear to be evenly distributed within the composites. Water immersion tests demonstrate the excellent interplay between the membranes and the aqueous environment. EIS experiments, performed with the in-plane and through-plane configurations, disclose the improvement of the proton transfer ability (σ) in both directions. At 120 °C, PBI/SGO 1:2 achieves the highest in-plane σ of 0.113 S cm−1, while PBI/SGO 1:3 shows the best through-plane σ of 0.025 S cm−1. The preference toward planar proton migration is confirmed by the computation of the anisotropy factor, which is attenuated to ≈0.5 with the aid of temperature. Based on these findings, the composites with large SGO content seem to possess great potential as alternative non-fluorinated proton exchange membranes.

In the past decade, significant European calls for research proposals have supported translational collaborative research on non-communicable and infectious diseases within the biomedical life sciences by bringing together interdisciplinary and multinational consortia. This research has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts’ societal impact. Research proposals should be thoughtfully designed to ensure that the research findings can be effectively translated into actionable policies. In addition, the choice of scientific methods plays a pivotal role in shaping the societal impact of research discoveries. Understanding the factors responsible for current unmet public health issues and medical needs is crucial for crafting innovative strategies for research policy interventions. A multistakeholder survey and a roundtable helped identify potential needs for consideration in the EU research and policy agenda. Based on survey findings, mental health disorders, metabolic syndrome, cancer, antimicrobial resistance, environmental pollution, and cardiovascular diseases were considered the public health challenges deserving prioritisation. In addition, early diagnosis, primary prevention, the impact of environmental pollution on disease onset and personalised medicine approaches were the most selected unmet medical needs. Survey findings enabled the formulation of some research-policies interventions (RPIs), which were further discussed during a multistakeholder online roundtable. The discussion underscored recent EU-level activities aligned with the survey-derived RPIs and facilitated an exchange of perspectives on public health and biomedical research topics ripe for interdisciplinary collaboration and warranting attention within the EU’s research and policy agenda. Actionable recommendations aimed at facilitating the translation of knowledge into transformative, science-based policies are also provided.

The GINGER (gyroscopes in general relativity) project foresees the construction of an array of large frame ring laser gyroscopes, rigidly connected to the Earth. Large frame ring laser gyroscopes are high-sensitivity instruments used to measure angular velocity with respect to the local inertial frame. In particular, they can provide sub-daily variations in the Earth rotation rate, a measurement relevant for geodesy and for fundamental physics at the same time. Sensitivity is the key point in determining the relevance of this instrument for fundamental science. The most recent progress in sensitivity evaluation, obtained on a ring laser prototype, indicates that GINGER should reach the level of 1 part in 1011 of the Earth’s rotation rate. The impact on fundamental physics of this kind of apparatus is reviewed.

En este artículo nos proponemos reflexionar sobre las características y las funciones que en la actualidad desempeñan las primeras áreas suburbanas de las ciudades de América Latina. Se trata de antiguos espacios periféricos, de varias generaciones, en los cuales se establecieron las primeras industrias, otras actividades productivas o equipamientos sanitarios y/o contornos del casco antiguo en los que se produjeron los primeros loteos residenciales y que, merced al proceso de metropolización, se han integrado a la ciudad central. Se trata de un ejercicio descriptivo cuyo objetivo fue recoger las conceptualizaciones y el conocimiento existentes con el fin de delinear pistas para el análisis de las antiguas periferias. El mismo se apoya en la revisión bibliográfica que, si bien no es exhaustiva, recoge casi un centenar de trabajos publicados en revistas nacionales e internacionales y en libros del área de la geografía crítica, la sociología urbana y el urbanismo a lo largo de décadas.

Abstract Background Amidst growing concern about the safety of sport-related repetitive subconcussive head impacts (RSHI), biofluid markers may provide sensitive, informative, and practical assessment of the effects of RSHI exposure. Objective This scoping review aimed to systematically examine the extent, nature, and quality of available evidence from studies investigating the effects of RSHI on biofluid markers, to identify gaps and to formulate guidelines to inform future research. Methods PRISMA extension for Scoping Reviews guidelines were adhered to. The protocol was pre-registered through publication. MEDLINE, Scopus, SPORTDiscus, CINAHL, PsycINFO, Cochrane Library, OpenGrey, and two clinical trial registries were searched (until March 30, 2022) using descriptors for subconcussive head impacts, biomarkers, and contact sports. Included studies were assessed for risk of bias and quality. Results Seventy-nine research publications were included in the review. Forty-nine studies assessed the acute effects, 23 semi-acute and 26 long-term effects of RSHI exposure. The most studied sports were American football, boxing, and soccer, and the most investigated markers were (in descending order): S100 calcium-binding protein beta (S100B), tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), phosphorylated tau (p-tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and hormones. High or moderate bias was found in most studies, and marker-specific conclusions were subject to heterogeneous and limited evidence. Although the evidence is weak, some biofluid markers—such as NfL—appeared to show promise. More markedly, S100B was found to be problematic when evaluating the effects of RSHI in sport. Conclusion Considering the limitations of the evidence base revealed by this first review dedicated to systematically scoping the evidence of biofluid marker levels following RSHI exposure, the field is evidently still in its infancy. As a result, any recommendation and application is premature. Although some markers show promise for the assessment of brain health following RSHI exposure, future large standardized and better-controlled studies are needed to determine biofluid markers’ utility.

Ocular artifacts, including blinks and saccades, pose significant challenges in the analysis of electroencephalographic (EEG) data, often obscuring crucial neural signals. This tutorial provides a comprehensive guide to the most effective methods for correcting these artifacts, with a focus on algorithms designed for both laboratory and real-world settings. We review traditional approaches, such as regression-based techniques and Independent Component Analysis (ICA), alongside more advanced methods like Artifact Subspace Reconstruction (ASR) and deep learning-based algorithms. Through detailed step-by-step instructions and comparative analysis, this tutorial equips researchers with the tools necessary to maintain the integrity of EEG data, ensuring accurate and reliable results in neurophysiological studies. The strategies discussed are particularly relevant for wearable EEG systems and real-time applications, reflecting the growing demand for robust and adaptable solutions in applied neuroscience.

Reanalysis-driven regional climate simulations using the Weather Research and Forecasting (WRF) model in New South Wales (NSW) and Australian Regional Climate Modelling (NARCliM) Version 2.0 are assessed for capturing precipitation extreme indices. Seven configurations of the WRF model driven by ECMWF (European Centre for Medium-Range Weather Forecasts) Reanalysis v5 (ERA5) for Australia from 1979 to 2020 at 20 km resolution are evaluated. We assess the spatiotemporal patterns of six selected Expert Team on Sector-Specific Climate Indices (ET-SCI) precipitation extremes by comparing regional climate model (RCM) simulations against gridded observations. The RCMs evaluated have varying levels of accuracy in simulating precipitation extremes. While they capture climatology and coefficient of variation of precipitation extremes relatively well, temporal correlation and trend reproduction present challenges. Some RCMs perform more effectively for specific extreme indices, while others encounter challenges in accurately replicating them. No single RCM excels in all aspects, highlighting the need to consider specific strengths when selecting RCMs for global climate model (GCM) driven simulations.

IntroductionModified Vaccinia Virus Ankara (MVA) is a safe vaccine vector inducing long- lasting and potent immune responses. MVA-mediated CD8+T cell responses are optimally induced, if both, direct- and cross-presentation of viral or recombinant antigens by dendritic cells are contributing.MethodsTo improve the adaptive immune responses, we investigated the role of the purinergic receptor P2X7 (P2RX7) in MVA-infected feeder cells as a modulator of cross-presentation by non-infected dendritic cells. The infected feeder cells serve as source of antigen and provide signals that help to attract dendritic cells for antigen take up and to license these cells for cross-presentation.ResultsWe demonstrate that presence of an active P2RX7 in major histocompatibility complex (MHC) class I (MHCI) mismatched feeder cells significantly enhanced MVA-mediated antigen cross-presentation. This was partly regulated by P2RX7-specific processes, such as the increased availability of extracellular particles as well as the altered cellular energy metabolism by mitochondria in the feeder cells. Furthermore, functional P2RX7 in feeder cells resulted in a delayed but also prolonged antigen expression after infection. DiscussionWe conclude that a combination of the above mentioned P2RX7-depending processes leads to significantly increased T cell activation via cross- presentation of MVA-derived antigens. To this day, P2RX7 has been mostly investigated in regards to neuroinflammatory diseases and cancer progression. However, we report for the first time the crucial role of P2RX7 for antigen- specific T cell immunity in a viral infection model.

A comprehensive understanding of the molecules that play key roles in the physiological and pathological homeostasis of the human intervertebral disc (IVD) remains challenging, as does the development of new therapeutic treatments. We recently found a positive correlation between IVD degeneration (IDD) and P2X7 receptor (P2X7R) expression increases both in the cytoplasm and in the nucleus. Using immunocytochemistry, reverse transcription PCR (RT-PCR), overexpression, and chromatin immunoprecipitation, we found that NFATc1 and hypoxia-inducible factor-1α (HIF-1α) are critical regulators of P2X7R. Both transcription factors are recruited at the promoter of the P2RX7 gene and involved in its positive and negative regulation, respectively. Furthermore, using the proximity ligation assay, we revealed that P2X7R and NFATc1 form a molecular complex and that P2X7R is closely associated with lamin A/C, a major component of the nuclear lamina. Collectively, our study identifies, for the first time, P2X7R and NFATc1 as markers of IVD degeneration and demonstrates that both NFATc1 and lamin A/C are interaction partners of P2X7R.

Abstract The mammalian DNA replication timing (RT) program is crucial for the proper functioning and integrity of the genome. The best-known mechanism for controlling RT is the suppression of late origins of replication in heterochromatin by RIF1. Here, we report that in antigen-activated, hypermutating murine B lymphocytes, RIF1 binds predominantly to early-replicating active chromatin and promotes early replication, but plays a minor role in regulating replication origin activity, gene expression and genome organization in B cells. Furthermore, we find that RIF1 functions in a complementary and non-epistatic manner with minichromosome maintenance (MCM) proteins to establish early RT signatures genome-wide and, specifically, to ensure the early replication of highly transcribed genes. These findings reveal additional layers of regulation within the B cell RT program, driven by the coordinated activity of RIF1 and MCM proteins.

We shall review the opportunities lent by ring lasers and atomic beams interferometry in order to reveal gravitomagnetic effects on Earth. Both techniques are based on the asymmetric propagation of waves in the gravitational field of a rotating mass; actually the times of flight for co- or counter-rotating closed paths turn out to be different. After discussing properties and limitations of the two approaches we shall describe the proposed GINGER experiment which is being developed for the Gran Sasso National Laboratories in Italy. The experimental apparatus will consist of a three-dimensional array of square rings, 6m × 6m, that is planned to reach a sensitivity in the order of 1prad/√Hertz or better. This sensitivity would be one order of magnitude better than the best existing ring, which is the G-ring in Wettzell, Bavaria, and would allow for the terrestrial detection of the Lense-Thirring effect and possibly of deviations from General Relativity. The possibility of using either the ring laser approach or atomic interferometry in a space mission will also be considered. The technology problems are under experimental study using both the German G-ring and the smaller G-Pisa ring, located at the Gran Sasso.