National Council for Scientific Research

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 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.15538. 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-2021, and supersedes data presented in the 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.

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show that this molecule can have several toxicological effects such as nephrotoxic, hepatotoxic, neurotoxic, teratogenic and immunotoxic. A role in the etiology of Balkan endemic nephropathy and its association to urinary tract tumors has been also proved. In this review, we will explore the general aspect of OTA: physico-chemical properties, toxicological profile, OTA producing fungi, contaminated food, regulation, legislation and analytical methods. Due to lack of sufficient information related to the molecular background, this paper will discuss in detail the recent advances in molecular biology of OTA biosynthesis, based on information and on new data about identification and characterization of ochratoxin biosynthetic genes in both Penicillium and Aspergillus species. This review will also cover the development of the molecular methods for the detection and quantification of OTA producing fungi in various foodstuffs.

In this work, we present for the first time undeniable evidence of nano-plastic occurrence due to solar light degradation of marine micro-plastics under controlled and environmentally representative conditions.

RATIONALE: Pulmonary fibrosis is a devastating as yet untreatable disease. We previously investigated the endogenous mediators released on lung injury and showed that uric acid is a danger signal activating Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in lung inflammation and fibrosis (Gasse et al., Am J Respir Crit Care Med 2009;179:903-913). OBJECTIVES: Here we address the role of extracellular adenosine triphosphate (eATP) in pulmonary inflammation and fibrosis. METHODS: ATP was quantified in bronchoalveolar lavage fluid (BALF) of control subjects and patients with idiopathic pulmonary fibrosis. The contribution of eATP as a danger signal was assessed in a murine model of lung fibrosis induced by airway-administered bleomycin (BLM), an intercalating agent that causes DNA strand breaks. MEASUREMENTS AND MAIN RESULTS: Fibrotic patients have elevated ATP content in BALF in comparison with control individuals. In mice, we report an early increase in eATP levels in BALF on BLM administration. Modulation of eATP levels with the ATP-degrading enzyme apyrase greatly reduced BLM-induced inflammatory cell recruitment, lung IL-1β, and tissue inhibitor of metalloproteinase (TIMP)-1 production, while administration of ATP-γS, a stable ATP derivative, enhanced inflammation. P2X(7) receptor-deficient mice presented dramatically reduced lung inflammation, with reduced fibrosis markers such as lung collagen content and matrix-remodeling proteins TIMP-1 and matrix metalloproteinase-9. The acute inflammation depends on a functional pannexin-1 hemichannel protein. In vitro, ATP is released by pulmonary epithelial cells on BLM-induced stress and this is partly dependent on the presence of functional P2X(7) receptor and pannexin-1 hemichannel. CONCLUSIONS: ATP released from BLM-injured lung cells constitutes a major endogenous danger signal that engages the P2X(7) receptor/pannexin-1 axis, leading to IL-1β maturation and lung fibrosis.

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.

Gut microbiota produces a wide and diverse array of metabolites that are an integral part of the host metabolome. The emergence of the gut microbiome-brain axis concept has prompted investigations on the role of gut microbiota dysbioses in the pathophysiology of brain diseases. Specifically, the search for microbe-related metabolomic signatures in human patients and animal models of psychiatric disorders has pointed out the importance of the microbial metabolism of aromatic amino acids. Here, we investigated the effect of indole on brain and behavior in rats. Indole is produced by gut microbiota from tryptophan, through the tryptophanase enzyme encoded by the tnaA gene. First, we mimicked an acute and high overproduction of indole by injecting this compound in the cecum of conventional rats. This treatment led to a dramatic decrease of motor activity. The neurodepressant oxidized derivatives of indole, oxindole and isatin, accumulated in the brain. In addition, increase in eye blinking frequency and in c-Fos protein expression in the dorsal vagal complex denoted a vagus nerve activation. Second, we mimicked a chronic and moderate overproduction of indole by colonizing germ-free rats with the indole-producing bacterial species Escherichia coli. We compared emotional behaviors of these rats with those of germ-free rats colonized with a genetically-engineered counterpart strain unable to produce indole. Rats overproducing indole displayed higher helplessness in the tail suspension test, and enhanced anxiety-like behavior in the novelty, elevated plus maze and open-field tests. Vagus nerve activation was suggested by an increase in eye blinking frequency. However, unlike the conventional rats dosed with a high amount of indole, the motor activity was not altered and neither oxindole nor isatin could be detected in the brain. Further studies are required for a comprehensive understanding of the mechanisms supporting indole effects on emotional behaviors. As our findings suggest that people whose gut microbiota is highly prone to produce indole could be more likely to develop anxiety and mood disorders, we addressed the issue of the inter-individual variability of indole producing potential in humans. An in silico investigation of metagenomic data focused on the tnaA gene products definitively proved this inter-individual variability.

Scientific innovation and obsolescence from specialization and fragmentation to hybridization the crumbling walls of the formal disciplines the interpenetration of disciplines - the process of hybridization gallery of hybrids - creative marginals crossroads - four illustrations.

This paper describes recent advances in speaker diarization with a multistage segmentation and clustering system, which incorporates a speaker identification step. This system builds upon the baseline audio partitioner used in the LIMSI broadcast news transcription system. The baseline partitioner provides a high cluster purity, but has a tendency to split data from speakers with a large quantity of data into several segment clusters. Several improvements to the baseline system have been made. First, the iterative Gaussian mixture model (GMM) clustering has been replaced by a Bayesian information criterion (BIC) agglomerative clustering. Second, an additional clustering stage has been added, using a GMM-based speaker identification method. Finally, a post-processing stage refines the segment boundaries using the output of a transcription system. On the National Institute of Standards and Technology (NIST) RT-04F and ESTER evaluation data, the multistage system reduces the speaker error by over 70% relative to the baseline system, and gives between 40% and 50% reduction relative to a single-stage BIC clustering system

Different approaches are available to compensate gait in persons with spinal cord injury, including passive orthoses, functional electrical stimulation (FES), and robotic exoskeletons. However, several drawbacks arise from each specific approach. Orthotic gait is energy-demanding for the user and functionally ineffective. FES uses the muscles as natural actuators to generate gait, providing not only functional but also psychological benefits to the users. However, disadvantages are also related to the early appearance of muscle fatigue and the control of joint trajectories. Robotic exoskeletons that provide joint moment compensation or substitution to the body during walking have been developed in recent years. Significant advances have been achieved, but the technology itself is not mature yet because of many limitations related to both physical and cognitive interaction as well as portability and energy-management issues. Meanwhile, the combination of FES technology and exoskeletons has emerged as a promising approach to both gait compensation and rehabilitation, bringing together technologies, methods, and rehabilitation principles that can overcome the drawbacks of each individual approach. This article presents an overview of hybrid lower-limb exoskeletons, related technologies, and advances in actuation and control systems. Also, we highlight the functional assessment of individuals with spinal cord injury.

OBJECTIVE: The objective of this study is to comprehensively define the genetic basis of early onset myasthenia gravis (EOMG). METHODS: We have carried out a 2-stage genome-wide association study on a total of 649 North European EOMG patients. Cases were matched 1:4 with controls of European ancestry. We performed imputation and conditional analyses across the major histocompatibility complex, as well as in the top regions of association outside the human leukocyte antigen (HLA) region. RESULTS: We observed the strongest association in the HLA class I region at rs7750641 (p = 1.2 × 10(-92) ; odds ratio [OR], 6.25). By imputation and conditional analyses, HLA-B*08 proves to be the major associated allele (p = 2.87 × 10(-113) ; OR, 6.41). In addition to the expected association with PTPN22 (rs2476601; OR, 1.71; p = 8.2 × 10(-10) ), an imputed coding variant (rs2233290) at position 151 (Pro→Ala) in the TNFAIP3-interacting protein 1, TNIP1, confers even stronger risk than PTPN22 (OR, 1.91; p = 3.2 × 10(-10) ). INTERPRETATION: The association at TNIP1 in EOMG implies disease mechanisms involving ubiquitin-dependent dysregulation of NF-κB signaling. The localization of the major HLA signal to the HLA-B*08 allele suggests that CD8(+) T cells may play a key role in disease initiation or pathogenesis.

Abstract Interaction between a collapsing bubble and a free surface is investigated theoretically and experimentally using high speed photography. A limit value for the distance from the free surface to the center of the bubble reported to its radius is found. Under this limit the free surface is not disturbed before the end of the collapse in the first approximation. Only in this case, the method of images can be used and the free surface be replaced by an image-source, symmetrical with respect to the free surface, to the sink representing the bubble. Above this limit, precise measurements of bubble deformation and motion are given. Just after the collapse of the bubble begins, observations show a singular perturbation on the free surface, with the formation of a thin spike directed towards the air. In all cases, buoyancy has no time to take effect, and the bubble is repelled from the free surface while the re-entering jet, formed during collapse, is oriented away from it.

Abstract Synthetic aperture radar (SAR) sensors are often used to characterize the surface of bare soils in agricultural environments. They enable the soil moisture and roughness to be estimated with constraints linked to the configurations of the sensors (polarization, incidence angle and radar wavelength). These key soil characteristics are necessary for different applications, such as hydrology and risk prediction. This article reviews the potential of currently operational SAR sensors and those planned for the near future to characterize soil surface as a function of users' needs. It details what it is possible to achieve in terms of mapping soil moisture and roughness by specifying optimal radar configurations and the precision associated with the estimation of soil surface characteristics. The summary carried out for the present article shows that mapping soil moisture is optimal with SAR sensors at low incidence angles (<35 ). This configuration, which enables an estimated moisture accuracy greater than 6% is possible several times a month taking into account all the current and future sensors. Concerning soil roughness, it is best mapped using three classes (smooth, moderately rough, and rough). Such mapping requires high‐incidence data, which is possible with certain current sensors (RADARSAT‐1 and ASAR both in band C). When L‐band sensors (ALOS) become available, this mapping accuracy should improve because the sensitivity of the radar signal to Soil Surface Characteristics (SSC) increases with wavelength. Finally, the polarimetric mode of certain imminent sensors (ALOS, RADARSAT‐2, TerraSAR‐X, etc.), and the possibility of acquiring data at very high spatial resolution (metre scale), offer great potential in terms of improving the quality of SSC mapping. Copyright © 2007 John Wiley & Sons, Ltd.

OBJECTIVES: To investigate, measure and assess the food consumption pattern of the adult population living in Beirut, Lebanon, and to identify inadequate or excessive intake of food groups particularly linked to non-communicable diseases. DESIGN: A cross-sectional food consumption survey was conducted in 2001. Dietary habits were assessed by means of a quantitative food-frequency questionnaire. SETTING: Dietary survey of the urban population (Beirut). SUBJECTS: Random sample of 444 adult subjects (aged 25-54 years) in Beirut. RESULTS: The mean consumption of food by the study population was estimated to be 3,030 g day(-1), providing an energy intake of 2,523.57 kcal day(-1). Fat contributed 38.9% to the average daily energy intake, protein 13.4% and carbohydrates 47.2%. Mean consumption of fruits and vegetables was approximately 367 g day(-1) and 45.3% of subjects consumed less than the recommended 400 g daily. Cereals contributed 324.5 g day(-1), providing 35.0% of daily energy intake, with bread being the most highly consumed (146.2 g day(-1)) in this food group. The mean intake of meat and poultry products was 91.7 g day(-1) and provided 8.8% of daily energy intake, with consumption of butchery products especially beef being the highest (47.6 g day(-1)) followed by poultry (36.1 g day(-1)). A low consumption of fish was noted (19.7 g day(-1)), with 73.6% of subjects consuming less than the recommended 2 servings of fish per week. Dairy products contributed 243.1 g day(-1) or 10.9% of daily energy intake, and milk was the least consumed dairy product (56.8% of consumers). The intake of added fats and oils, excluding those in cooked recipes, was 20.4 g day(-1); olive oil was not used in cooking but was added solely at the table and its mean intake was 5 g day(-1). The consumption of butter was low (0.86 g day(-1)) and vegetable oil was the type of fat mostly used in cooking. The average intake of alcoholic beverages was low (33.6 g day(-1)), accounting for 0.7% of total energy intake. Women had significantly higher intakes of milk, dairy products, vegetables and coffee than men (P < 0.05). The percentage of women who reported the use of low-fat items was significantly higher than that of men. Younger people (25-34 years) ate significantly more meat, sugar, alcoholic beverages and soft drinks, and consumed significantly less cooked vegetables and legumes, than older ones (P < 0.05). CONCLUSIONS: The rather high contribution of fat to daily energy intake, the low intake of fish and the relatively high percentage of people consuming less than the recommended amount of fruits and vegetables observed in this study suggest that the adult Lebanese population is at increased risk of cardiovascular diseases, obesity and other non-communicable diseases, which provides the basis for recommending increased intakes of fish, particularly fatty fish, and fruits and vegetables.

Cooperation in cellular networks is a promising scheme to improve system performance, especially for cell-edge users. In this work, stochastic geometry is used to analyze cooperation models where the positions of base stations follow a Poisson point process distribution and where Voronoi cells define the planar areas associated with them. For the service of each user, either one or two base stations are involved. If two, these cooperate by exchange of user data and channel related information with conferencing over some backhaul link. Our framework generally allows for variable levels of channel information at the transmitters. This paper is focused on a case of limited information based on Willems' encoding. The total per-user transmission power is split between the two transmitters and a common message is encoded. The decision for a user to choose service with or without cooperation is directed by a family of geometric policies, depending on its relative position to its two closest base stations. An exact expression of the network coverage probability is derived. Numerical evaluation shows average coverage benefits of up to 17% compared to the non-cooperative case. Various other network problems of cellular cooperation, like the fully adaptive case, can be analyzed within our framework.

Over the past decade, several influential papers examining the relationship between scientific knowledge and attitudes toward science have been published. The 1992 Eurobarometer has been the preferred source of data for analysis, and a number of suggestive conclusions regarding the extent and nature of the links between knowledge and attitudes have been proposed. Summated scales were built through principal component analysis of the attitudinal items and reliability analysis, but little attention has been paid to the content of the attitudinal items and to the metric and conceptual weaknesses of the scales. A more parsimonious revision of the data, carried out here, shows that the measures used are fuzzy and, as a consequence, the empirical support for some published results is very limited. We suggest that more theoretical effort should be devoted to the design of questionnaires and to the combined use of statistical exploratory techniques and qualitative analysis in the interpretation of the data.

The outbreak of the novel coronavirus disease in 2019 (COVID-19) caused a plethora of challenges worldwide and tested healthcare systems across the six continents. Lebanon had recently faced harsh political and economic crises. We aim to describe the effect of COVID-19 on an already crisis-stricken country. A descriptive analysis of the burden of COVID-19 pandemic on Lebanon was performed. Relevant data on COVID-19 was retrieved from the Lebanese Ministry of Public Health from February 21 till June 13th, 2020. Results obtained were analyzed and a literature review was performed. 1422 confirmed COVID-19 cases were identified and reported in Lebanon by June 13th, 2020, comprising an incidence rate of 208/million persons. There has been a total of 31 deaths thus far, with a reported death rate of 5/million persons. The age group with the highest number of cases was 20-29 years. Beirut was the district with the highest number of cases (18%). The COVID-19 crisis has impacted the country on a multifactorial level. COVID-19 could not have come at a worse time for Lebanon. The country is on brink of bankruptcy, the healthcare system is struggling for survival and the government is striving to regain the trust of the population.

Drought is a serious natural hazard with far-reaching impacts including soil damages, economic losses, and threatening the livelihood and health of local residents. The goal of the present work was to monitor the vegetation health across Lebanon in 2014 using remote sensing techniques. Landsat images datasets, with a spatial resolution of 30 m and from different platforms, were used to identify the VCI (Vegetation Condition Index) and TCI (Temperature Condition Index). The VCI was based on the Normalized Difference Vegetation Index (NDVI) datasets. The TCI used land surface temperature (LST) datasets. As a result, the VHI (Vegetation Health Index) was produced and classified into five categories: extreme, severe, moderate, mild, and no drought. The results show practically no extreme drought (~0.27 km2) in the vegetated area in Lebanon during 2014. Moderate to severe drought mainly occurred in the north of Lebanon (i.e., the Amioun region and the plain of Akkar). The Tyr region and the Bekaa valley experienced a low level of drought (mild drought). This approach allows decision makers to monitor, investigate and resolve drought conditions more effectively.

The cerebrospinal fluid (CSF) is a major part of the extracellular fluid of the central nervous system. The function of the CSF and the tissue that secretes it, the choroid plexus (CP) has traditionally been thought as providing the brain with essential nutrients, removing products of neuronal activity of the central nervous system, and providing mechanical support for the brain's fragile cellular network. More recent studies suggest, however, that the CP and CSF system play a much more active role in the function of the central nervous system being a target, source and pathway for neuroendocrine signaling within the brain.

On 9 July A.D. 551, a large earthquake, followed by a tsunami, destroyed most of the coastal cities of Phoenicia (modern-day Lebanon). Tripoli is reported to have “drowned,” and Berytus (Beirut) did not recover for nearly 1300 yr afterwards. Geophysical data from the Shalimar survey unveil the source of this event, which may have had a moment magnitude (Mw) of 7.5 and was arguably one of the most devastating historical submarine earthquakes in the eastern Mediterranean: rupture of the offshore, hitherto unknown, ∼100–150-km-long active, east-dipping Mount Lebanon thrust. Deep-towed sonar swaths along the base of prominent bathymetric escarpments reveal fresh, west-facing seismic scarps that cut the sediment-smoothed seafloor. The Mount Lebanon thrust trace comes closest (∼8 km) to the coast between Beirut and Enfeh, where, as 13 14C-calibrated ages indicate, a shoreline-fringing vermetid bench suddenly emerged by ∼80 cm in the sixth century A.D. At Tabarja, the regular vertical separation (∼1 m) of higher fossil benches suggests uplift by three more earthquakes of comparable size since the Holocene sea level reached a maximum ca. 7–6 ka, implying a 1500-1750 yr recurrence time. Unabated thrusting on the Mount Lebanon thrust likely drove the growth of Mount Lebanon since the late Miocene.

Approximately 4 yr of campaign and continuous Global Positioning System (GPS) measurements across the Dead Sea fault system (DSFS) in Lebanon provide direct measurements of interseismic strain accumulation along a 200‐km‐long restraining bend in this continental transform fault. Late Cenozoic transpression within this restraining bend has maintained more than 3000 m of topography in the Mount Lebanon and Anti‐Lebanon ranges. The GPS velocity field indicates 4–5 mm yr−1 of relative plate motion is transferred through the restraining bend to the northern continuation of the DSFS in northwestern Syria. Near‐field GPS velocities are generally parallel to the major, left‐lateral strike‐slip faults, suggesting that much of the expected convergence across the restraining bend is likely accommodated by different structures beyond the aperture of the GPS network (e.g. offshore Lebanon and, possibly, the Palmyride fold belt in SW Syria). Hence, these geodetic results suggest a partitioning of crustal deformation involving strike‐slip displacements in the interior of the restraining bend, and crustal shortening in the outer part of the restraining bend. Within the uncertainties, the GPS‐based rates of fault slip compare well with Holocene‐averaged estimates of slip along the two principal strike‐slip faults: the Yammouneh and Serghaya faults. Of these two faults, more slip occurs on the Yammouneh fault, which constitutes the primary plate boundary structure between the Arabia and Sinai plates. Hence, the Yammouneh fault is the structural linkage that transfers slip to the northern part of the transform in northwestern Syria. From the perspective of the regional earthquake hazard, the Yammouneh fault is presently locked and accumulating interseismic strain.