Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes

<p>Abstract</p> <p>Background</p> <p>The melanocortin (MC) receptors have a key role in regulating body weight and pigmentation. They belong to the rhodopsin family of G protein-coupled receptors (GPCRs). The purpose of this study was to identify ancestral MC receptors in agnathan, river lamprey.</p> <p>Results</p> <p>We report cloning of two MC receptors from river lamprey. The lamprey receptors, designated MCa and MCb, showed orthology to the MC1 and MC4 receptor subtypes, respectively. The molecular clock analysis suggested that lamprey MC receptor genes were not duplicated recently and diverged from each other more than 400 MYR ago. Expression and pharmacological characterization showed that the lamprey MCa receptor was able to bind and be activated by both lamprey and human MSH peptides. The lamprey MCa receptor had relatively high affinity for ACTH derived peptides similarly to the fish MC receptors. We found that both of the lamprey MC receptors were expressed in skin, while the MCb receptor was also found in liver, heart and skeletal muscle.</p> <p>Conclusion</p> <p>This study shows presence of MC receptors in agnathans indicating early signs of specific functions of melanocortin receptor subtypes.</p

TCO evaluation in physical asset management : benefits and limitations for industrial adoption

Part 1: Knowledge-Based Performance ImprovementInternational audienceNowadays, the evaluation of the total cost of ownership (TCO) of an asset for supporting informed decision-making both for investments and managerial issues within the asset management framework is gaining increasing attention in industry. Nevertheless its application in practice is still limited. The aim of this paper is to analyze the benefits and limitations of the adoption of TCO evaluation in asset management. Based on a literature review, the paper defines a framework that categorizes the benefits and potential applications that a TCO model can have for different stakeholders. Together with that, industry related issues that influence its implementation are also considered. Finally, empirical evidences are analyzed through a multiple case study to understand if those benefits are recognized in practice and which are the limitations for the practical adoption of a TCO model that should allow exploiting such benefits

Development of CRISPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria

The emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. Here we report the development of a series of CRISPR-Cas13a-based antibacterial nucleocapsids, termed CapsidCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus by recognizing corresponding antimicrobial resistance genes. CapsidCas13a constructs are generated by packaging programmed CRISPR-Cas13a into a bacteriophage capsid to target antimicrobial resistance genes. Contrary to Cas9-based antimicrobials that lack bacterial killing capacity when the target genes are located on a plasmid, the CapsidCas13a(s) exhibit strong bacterial killing activities upon recognizing target genes regardless of their location. Moreover, we also demonstrate that the CapsidCas13a(s) can be applied to detect bacterial genes through gene-specific depletion of bacteria without employing nucleic acid manipulation and optical visualization devices. Our data underscore the potential of CapsidCas13a(s) as both therapeutic agents against antimicrobial-resistant bacteria and nonchemical agents for detection of bacterial genes

Regulatory Approaches to Managing Skilled Migration: Indonesian Nurses in Japan

This article examines the Japan–Indonesia Economic Partnership Agreement, an agreement that has allowed Japan to supplement its local healthcare workforce while continuing to sidestep the thorny issue of labour and immigration policy reform and Indonesia to increase its skilled workers’ access to the Japanese labour market at a time when it was making a concerted effort to reorient migrant labour flows away from informal sector occupations. Despite the programme’s many problems, it has contributed to the use of trade agreements as a mechanism for regulating labour migration, and so to the normalisation of migrant labour as a tradable commodity rather than a discrete area of policy-making, with all the attendant risks that normalisation brings

Comparative genomics approach to detecting split-coding regions in a low-coverage genome: lessons from the chimaera Callorhinchus milii (Holocephali, Chondrichthyes)

Recent development of deep sequencing technologies has facilitated de novo genome sequencing projects, now conducted even by individual laboratories. However, this will yield more and more genome sequences that are not well assembled, and will hinder thorough annotation when no closely related reference genome is available. One of the challenging issues is the identification of protein-coding sequences split into multiple unassembled genomic segments, which can confound orthology assignment and various laboratory experiments requiring the identification of individual genes. In this study, using the genome of a cartilaginous fish, Callorhinchus milii, as test case, we performed gene prediction using a model specifically trained for this genome. We implemented an algorithm, designated ESPRIT, to identify possible linkages between multiple protein-coding portions derived from a single genomic locus split into multiple unassembled genomic segments. We developed a validation framework based on an artificially fragmented human genome, improvements between early and recent mouse genome assemblies, comparison with experimentally validated sequences from GenBank, and phylogenetic analyses. Our strategy provided insights into practical solutions for efficient annotation of only partially sequenced (low-coverage) genomes. To our knowledge, our study is the first formulation of a method to link unassembled genomic segments based on proteomes of relatively distantly related species as references

Is the orbit of the exoplanet WASP-43b really decaying? TESS and MuSCAT2 observations confirm no detection

We thank Dr. S. Hoyer from the Laboratoire d'Astrophysique de Marseille (LAM) in France for the helpful discussions. We also thank the anonymous reviewer for the helpful comments and suggestions. This work was supported by the Erasmus+ grant number 2017-1-CZ01-KA203-035562, by the VEGA grant of the Slovak Academy of Sciences number 2/0031/18, by an ESA PRODEX grant under contracting with the ELTE University, by the GINOP number 2.3.2-15-2016-00003 of the Hungarian National Research, Development and Innovation Office, and by the City of Szombathely under agreement number 67.177-21/2016. This paper includes data collected with the TESS mission, obtained from the MAST data archive at the Space Telescope Science Institute (STScI). Funding for the TESS mission is provided by the NASA Explorer Program. STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium).Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. This article is based on observations made with the MuSCAT2 instrument, developed by ABC, at Telescopio Carlos Sanchez operated on the island of Tenerife by the IAC in the Spanish Observatorio del Teide. This work was partly financed by the Spanish Ministry of Economics and Competitiveness through grant number PGC2018098153-B-C31. This work was partly supported by JSPS KAKENHI grant numbers JP17H04574, JP18H01265 and JP18H05439, and JST PRESTO grant number JPMJPR1775. This work was partly supported by Grant-in-Aid for JSPS Fellows, grant number JP20J21872. TP acknowledges support from the Slovak Research and Development Agency - the contract No. APVV-20-0148. MT was supported by MEXT/JSPS KAKENHI grant numbers 18H05442, 15H02063, and 22000005. AC acknowledges financial support from the State Agency for Research of the Spanish MCIU through the `Center of Excellence Severo Ochoa' award for the Instituto de Astrophysics of Andalusia (SEV-2017-0709). We acknowledge funding from the European Research Council under the European Union's Horizon 2020 research and innovation program under grant agreement number 694513.Up to now, WASP-12b is the only hot Jupiter confirmed to have a decaying orbit. The case of WASP-43b is still under debate. Recent studies preferred or ruled out the orbital decay scenario, but further precise transit timing observations are needed to definitively confirm or refute the period change of WASP-43b. This possibility is given by the Transiting Exoplanet Survey Satellite (TESS) space telescope. In this work, we used the available TESS data, multicolour photometry data obtained with the Multicolor Simultaneous Camera for studying Atmospheres of Transiting exoplanets 2 (MuSCAT2) and literature data to calculate the period change rate of WASP-43b and to improve its precision, and to refine the parameters of the WASP-43 planetary system. Based on the observed-minus-calculated data of 129 mid-transit times in total, covering a time baseline of about 10 yr, we obtained an improved period change rate of (P)over dot = -0.6 +/- 1.2 ms yr(-1) that is consistent with a constant period well within 1 sigma. We conclude that new TESS and MuSCAT2 observations confirm no detection of WASP-43b orbital decay.Erasmus+ grant 2017-1-CZ01-KA203-035562VEGA grant of the Slovak Academy of Sciences 2/0031/18ESA PRODEX grantELTE UniversityNational Research, Development & Innovation Office (NRDIO) - Hungary 2.3.2-15-2016-00003City of Szombathely 67.177-21/2016National Aeronautics & Space Administration (NASA) NAS 5-26555Gaia Multilateral AgreementSpanish Ministry of Economics and Competitiveness PGC2018098153-B-C31Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) JP17H04574 JP18H01265 JP18H05439JST PRESTO grant JPMJPR1775Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science JP20J21872Slovak Research and Development Agency APVV-20-0148Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) 18H05442 15H02063 22000005State Agency for Research of the Spanish MCIU through the 'Center of Excellence Severo Ochoa' award for the Instituto de Astrophysics of Andalusia SEV-2017-0709European Research Council under the European Union's Horizon 2020 research and innovation program 69451

Acute Homeostatic Responses to Increased Fat Consumption in MCH1R Knockout Mice

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide which has been shown to regulate energy homeostasis. Using genetic knockout mice lacking the MCH1 receptor (MCH1R), we investigated how these mice adapt to metabolic changes caused by excessive caloric consumption. We show that the MCH system is one of the players mediating behavioral and metabolic responses upon increased caloric consumption. MCH1R knockout mice showed decreased tendency of food intake upon exposure to a high-fat diet. They also are resistant to gain weight upon high-fat diet by increasing fat metabolism. Therefore, the MCH system is important in regulating metabolic responses upon various environmental stimuli such as high-fat diet

An Earth-sized Planet around an M5 Dwarf Star at 22 pc

We report on the discovery of an Earth-sized transiting planet (R p = 1.015 ± 0.051 R ⊕) in a P = 4.02 day orbit around K2-415 (EPIC 211414619), an M5V star at 22 pc. The planet candidate was first identified by analyzing the light-curve data obtained by the K2 mission, and it is here shown to exist in the most recent data from TESS. Combining the light curves with the data secured by our follow-up observations, including high-resolution imaging and near-infrared spectroscopy with IRD, we rule out false-positive scenarios, finding a low false-positive probability of 2 × 10−4. Based on IRD’s radial velocities of K2-415, which were sparsely taken over three years, we obtain a planet mass of 3.0 ± 2.7 M ⊕ (M p < 7.5 M ⊕ at 95% confidence) for K2-415b. Being one of the lowest-mass stars (≈0.16 M ⊙) known to host an Earth-sized transiting planet, K2-415 will be an interesting target for further follow-up observations, including additional radial velocity monitoring and transit spectroscopy

Validation and atmospheric exploration of the sub-Neptune TOI-2136b around a nearby M3 dwarf

Context. The NASA space telescope TESS is currently in the extended mission of its all-sky search for new transiting planets. Of the thousands of candidates that TESS is expected to deliver, transiting planets orbiting nearby M dwarfs are particularly interesting targets since they provide a great opportunity to characterize their atmospheres by transmission spectroscopy. Aims. We aim to validate and characterize the new sub-Neptune-sized planet candidate TOI-2136.01 orbiting a nearby M dwarf (d = 33.36 +/- 0.02 pc, T-eff = 3373 +/- 108 K) with an orbital period of 7.852 days. Methods. We use TESS data, ground-based multicolor photometry, and radial velocity measurements with the InfraRed Doppler (IRD) instrument on the Subaru Telescope to validate the planetary nature of TOI-2136.01, and estimate the stellar and planetary parameters. We also conduct high-resolution transmission spectroscopy to search for helium in its atmosphere. Results. We confirm that TOI-2136.01 (now named TOI-2136b) is a bona fide planet with a planetary radius of R-p = 2.20 +/- 0.07 R-circle plus and a mass of M-p = 4.7(-2.6)(+3.1) M-circle plus. We also search for helium 10830 angstrom absorption lines and place an upper limit on the equivalent width of &lt;7.8 m angstrom and on the absorption signal of &lt;1.44% with 95% confidence. Conclusions. TOI-2136b is a sub-Neptune transiting a nearby and bright star (J = 10.8 mag), and is a potentially hycean planet, which is a new class of habitable planets with large oceans under a H-2-rich atmosphere, making it an excellent target for atmospheric studies to understand the formation, evolution, and habitability of the small planets

Carbenic nitrile imines: Properties and reactivity

Structures and properties of nitrile imines were investigated computationally at B3LYP and CCSD(T) levels. Whereas NBO analysis at the B3LYP DFT level invariably predicts a propargylic electronic structure, CCSD(T) calculations permit a clear distinction between propargylic, allenic, and carbenic structures. Nitrile imines with strong IR absorptions above ca. 2150 cm-1 have propargylic structures with a CN triple bond (RCNNSiMe 3 and R2BCNNBR2), and those with IR absorptions below ca. 2150 cm-1 are allenic (HCNNH, PhCNNH, and HCNNPh). Nitrile imines lacking significant cumulenic IR absorptions at 1900-2200 cm -1 are carbenic (R-(C:)-N=N-R′). Electronegative but lone pair-donating groups NR2, OR, and F stabilize the carbenic form of nitrile imines in the same way they stabilize "normal" singlet carbenes, including N-heterocyclic carbenes. NBO analyses at the CCSD(T) level confirm the classification into propargylic, allenic, and carbenic reactivity types. Carbenic nitrile imines are predicted to form azoketenes 21 with CO, to form [2+2] and [2+4] cycloadducts and borane adducts, and to cyclize to 1H-diazirenes of the type 24 in mildly exothermic reactions with activation energies in the range 29-38 kcal/mol. Such reactions will be readily accessible photochemically and thermally, e.g., under the conditions of matrix photolysis and flash vacuum thermolysis