Arginine 125 is an essential residue for the function of MRAP2

MRAP2 is a small simple transmembrane protein arranged in a double antiparallel topology on the plasma membrane. It is expressed in the paraventricular nucleus of the hypothalamus, where it interacts with various G protein-coupled receptors, such as the prokineticin receptors, and regulates energy expenditure and appetite. The aim of this work was to analyze the functional role of the specific arginine residue at position 125 of MRAP2, which affects protein conformation, dimer formation, and PKR2 binding. Results obtained with the MRAP2 mutants R125H and R125C, which are found in human patients with extreme obesity, and mouse MRAP2, in which arginine 125 is normally replaced by histidine, were compared with those obtained with human MRAP2. Understanding the mechanism by which MRAP2 regulates G protein-coupled receptors helps in elucidating the metabolic pathways involved in metabolic dysfunction and in developing new drugs as specific targets of the MRAP2-PKR2 complex

Abnormal Pain Sensation in Mice Lacking the Prokineticin Receptor PKR2: Interaction of PKR2 with Transient Receptor Potential TRPV1 and TRPA1

The amphibian Bv8 and the mammalian prokineticin 1 (PROK1) and 2 (PROK2) are new chemokine-like protein ligands acting on two G protein-coupled receptors, prokineticin receptor 1 (PKR1) and 2 (PKR2), participating to the mediation of diverse physiological and pathological processes. Prokineticins (PKs), specifically activating the prokineticin receptors (PKRs) located in several areas of the central and peripheral nervous system associated with pain, play a fundamental role in nociception. In this paper, to improve the understanding of the prokineticin system in the neurobiology of pain, we investigated the role of PKR2 in pain perception using pkr2 gene-deficient mice. We observed that, compared to wildtype, pkr2-null mice were more resistant to nociceptive sensitization to temperatures ranging from 46 to 48 \ub0C, to capsaicin and to protons, highlighting a positive interaction between PKR2 and the non-selective cation channels TRPV1. Moreover, PKR2 knock-out mice showed reduced nociceptive response to cold temperature (4 \ub0C) and to mustard oil-induced inflammatory hyperalgesia, suggesting a functional interaction between PKR2 and transient receptor potential ankyrin 1 ion (TRPA1) channels. This notion was supported by experiments in dorsal root ganglia (DRG) cultures from pkr1 and\u2013pkr2-null mice, demonstrating that the percentage of Bv8-responsive DRG neurons which were also responsive to mustard oil was much higher in PKR1 12/ 12 than in PKR2 12/ 12 mice. Taken together, these findings suggest a functional interaction between PKR2 and TRP channels in the development of hyperalgesia. Drugs able to directly or indirectly block these targets and/or their interactions may represent potential analgesics

Cercetari privind comportarea unor specii legumicole în ghivece şi containere

The paper presents the research results regarding the evaluation of morphological, physiological and production characteristics in some vegetable plants grown in pots and containers. The vegetable plants studiedwere: cherry tomatoes, sweet peppers, climbing beans, dwarf beans, oregano and lovage, and for pot culture: hot peppers, basil, salad, thyme, dill and parsley. Remarkable results were obtained for the following vegetable species: cherry tomatoes 1656.0 g / pl ant andpepper 2305g / pl for container culture, and for pot culture the results were: hot pepper, 351.3g / pl and salad 250.0 g / pl

Halogenated triazinediones behave as antagonists of PKR1: in vitro and in vivo pharmacological characterization

Different prokineticin receptor antagonists, based on the triazinedione scaffold, were synthesized by a new efficient method. Here we demonstrated that 5-benzyltriazinedionessubstituted in position para of the benzyl group with halogens provide compounds endowed with interesting selectivity for the Prokineticin receptor 1 (PKR1). BRET technology indicates that such substitutionresults in increased affinity for thePKR1.The affinity for PKR2, always in M range, was never significantly affected by the para-halogen-benzyl pharmacophores. The analog bearing a para-bromobenzyl pharmacophore (PC-25) displayed the highest affinity for PKR1 (~18 times higher than the reference PC-1 that bears apara-ethyl benzyl group) and the highest selectivity (~300 times). The other halogen substitutedanalogs (PC-7, PC-18 and PC-35), showed selectivity for PKR1 more than 100 times higher than for PKR2. Using transgenic mice lacking one of the two PKRs we demonstrated that all these compounds were able to abolish the Bv8-induced hyperalgesia in mice still expressing the PKR1 at doses lower than those necessary to abolish hyperalgesia in mice expressing only the PKR2. The dose ratio reflected the in- vitro evaluated receptor selectivity

Studii preliminare privind cultura plantelor legumicole în ghivece şi containere

This paper presents a literature review of the vegetable growing in pots and containers. Growing vegetables in this system it is known for a long time in the countries of Western Europe and in some areas of our country. Adopting this system in Romania requires in-depth studies regarding: the suitable species, the type of pots and soil recipes needed, crop establishment and maintenance (fertilizers aplication, irrigation) and, in some cases, optimization of the certain referring to light and placement of pots and containers. This cultivation system is spread mainly in peri-urban areas were the interest among gardeners to grow their own crops and secure their vegetable needs is high and has a favorable environment. Vegetable plants cultivated in pots and containers present a large diversity worldwide but, within this diversity, the climatic conditions from our country must be appropriate for an efficient activity

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Landslide databases in the Geological Surveys of Europe

Acceso electrónico sólo desde el IGMELandslides are one of the most widespread geohazards in Europe, producing significant social and economic impacts. Rapid population growth in urban areas throughout many countries in Europe and extreme climatic scenarios can considerably increase landslide risk in the near future. Variability exists between European countries in both the statutory treatment of landslide risk and the use of official assessment guidelines. This suggests that a European Landslides Directive that provides a common legal framework for dealing with landslides is necessary. With this long-term goal in mind, this work analyzes the landslide databases from the Geological Surveys of Europe focusing on their interoperability and completeness. The same landslide classification could be used for the 849,543 landslide records from the Geological Surveys, from which 36% are slides, 10% are falls, 20% are flows, 11% are complex slides, and 24% either remain unclassified or correspond to another typology. Most of them are mapped with the same symbol at a scale of 1:25,000 or greater, providing the necessary information to elaborate European-scale susceptibility maps for each landslide type. A landslide density map was produced for the available records from the Geological Surveys (LANDEN map) showing, for the first time, 210,544 km2 landslide-prone areas and 23,681 administrative areas where the Geological Surveys from Europe have recorded landslides. The comparison of this map with the European landslide susceptibility map (ELSUS 1000 v1) is successful for most of the territory (69.7%) showing certain variability between countries. This comparison also permitted the identification of 0.98 Mkm2 (28.9%) of landslide-susceptible areas without records from the Geological Surveys, which have been used to evaluate the landslide database completeness. The estimated completeness of the landslide databases (LDBs) from the Geological Surveys is 17%, varying between 1 and 55%. This variability is due to the different landslide strategies adopted by each country. In some of them, landslide mapping is systematic; others only record damaging landslides, whereas in others, landslide maps are only available for certain regions or local areas. Moreover, in most of the countries, LDBs from the Geological Surveys co-exist with others owned by a variety of public institutions producing LDBs at variable scales and formats. Hence, a greater coordination effort should be made by all the institutions working in landslide mapping to increase data integration and harmonization.Earth Observation and Geohazards Expert Group (EOEG), EuroGeoSurveys, the Geological Surveys of Europe, BélgicaGeohazards InSAR Laboratory and Modeling Group, Instituto Geológico y Minero de España, EspañaRisk and Prevention Division, Bureau de Recherches Géologiques et Minières, FranciaEngineering Geology Department, Institute of Geology and Mineral Exploration, GreciaGeoHazard team, Geological Institute of Romania, RumaníaGeological Survey of Slovenia, EsloveniaCroatian Geological Survey, CroaciaItalian Institute for Environmental Protection and Research, Geological Survey of Italy, ItaliaSwiss Federal Office for the Environment, SuizaGeological Survey of Austria, AustriaPolish Geological Institute, National Research Institute, PoloniaGeological Survey of Ireland, IrlandaCzech Geological Survey, República ChecaFederal Institute for Geosciences and Natural Resources, AlemaniaGeological Survey of Norway, NoruegaCyprus Geological Survey, ChipreGeological Survey of Sweden, SueciaInstitut Cartogràfic i Geològic de Catalunya, EspañaBritish Geological Survey, Reino UnidoGeological Survey of Slovakia, EslovaquiaGeological Survey of Lithuania, LituaniaFederalni zavod za geologiju, Bosnia y HerzegovinaGeological Survey of Estonia, EstoniaLaboratório Nacional de Energia e Geologia, PortugalGeological Survey of Hungary, HungríaNorwegian Water and energy Directorate of Norway, Norueg