The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

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

Obliquity measurement and atmospheric characterization of the WASP-74 planetary system

We present new transit observations of the hot Jupiter WASP-74 b ($T_\mathrm{eq} \sim$ 1860 K) using the high-resolution spectrograph HARPS-N and the multi-colour simultaneous imager MuSCAT2. We refine the orbital properties of the planet and its host star, and measure its obliquity for the first time. The measured sky-projected angle between the stellar spin-axis and the planet's orbital axis is compatible with an orbit well-aligned with the equator of the host star ($\lambda = 0.77\pm0.99 \mathrm{deg}$). We are not able to detect any absorption feature of H$\alpha$, or any other atomic spectral features, in its high-resolution transmission spectra due to low S/N at the line cores. Despite previous claims regarding the presence of strong optical absorbers such TiO and VO gases in the atmosphere of WASP-74 b, the new ground-based photometry combined with a reanalysis of previously reported observations from the literature shows a slope in the low-resolution transmission spectrum steeper than expected from Rayleigh scattering alone.Comment: Accepted for publication in Astronomy & Astrophysics. 12 pages, 8 figures, 5 table

IFSO (International Federation for Surgery of Obesity and Metabolic Disorders) Consensus Conference Statement on One-Anastomosis Gastric Bypass (OAGB-MGB): Results of a Modified Delphi Study

Background: One-anastomosis gastric bypass (OAGB-MGB) is currently the third performed primary bariatric surgical procedure worldwide. However, the procedure is hampered by numerous controversies and there is considerable variability in surgical technique, patient selection, and pre- and postoperative care among the surgeons performing this procedure. This paper reports the results of a modified Delphi consensus study organized by the International Federation for Surgery of Obesity and Metabolic Disorders (IFSO). Methods: Fifty-two internationally recognized bariatric experts from 28 countries convened for voting on 90 consensus statements over two rounds to identify those on which consensus could be reached. Inter-voter agreement of ≥ 70% was considered consensus, with voting participation ≥ 80% considered a robust vote. Results: At least 70% consensus was achieved for 65 of the 90 questions (72.2% of the items), 61 during the first round of voting and an additional four in the second round. Where consensus was reached on a binary agree/disagree or yes/no item, there was agreement with the statement presented in 53 of 56 instances (94.6%). Where consensus was reached on a statement where options favorable versus unfavorable to OAGB-MGB were provided, including statements in which OAGB-MGB was compared to another procedure, the response option favorable to OAGB-MGB was selected in 13 of 23 instances (56.5%). Conclusion: Although there is general agreement that the OAGB-MGB is an effective and usually safe option for the management of patients with obesity or severe obesity, numerous areas of non-consensus remain in its use. Further empirical data are needed

Radial velocity confirmation of K2-100b: A young, highly irradiated, and low-density transiting hot Neptune

We present a detailed analysis of HARPS-N radial velocity observations of K2-100, a young and active star in the Praesepe cluster, which hosts a transiting planet with a period of 1.7 d. We model the activity-induced radial velocity variations of the host star with a multidimensional Gaussian Process framework and detect a planetary signal of 10.6 \ub1 3.0 m s−1, which matches the transit ephemeris, and translates to a planet mass of 21.8 \ub1 6.2 M. We perform a suite of validation tests to confirm that our detected signal is genuine. This is the first mass measurement for a transiting planet in a young open cluster. The relatively low density of the planet, 2.04+−006661 g cm−3, implies that K2-100b retains a significant volatile envelope. We estimate that the planet is losing its atmosphere at a rate of 1011–1012 g s−1 due to the high level of radiation it receives from its host star

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 <7.8 m angstrom and on the absorption signal of <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

K2-280b -- a low density warm sub-Saturn around a mildly evolved star

We present an independent discovery and detailed characterisation of K2-280b, a transiting low density warm sub-Saturn in a 19.9-day moderately eccentric orbit (e = 0.35_{-0.04}^{+0.05}) from K2 campaign 7. A joint analysis of high precision HARPS, HARPS-N, and FIES radial velocity measurements and K2 photometric data indicates that K2-280b has a radius of R_b = 7.50 +/- 0.44 R_Earth and a mass of M_b = 37.1 +/- 5.6 M_Earth, yielding a mean density of 0.48_{-0.10}^{+0.13} g/cm^3. The host star is a mildly evolved G7 star with an effective temperature of T_{eff} = 5500 +/- 100 K, a surface gravity of log(g) = 4.21 +/- 0.05 (cgs), and an iron abundance of [Fe/H] = 0.33 +/- 0.08 dex, and with an inferred mass of M_star = 1.03 +/- 0.03 M_sun and a radius of R_star = 1.28 +/- 0.07 R_sun. We discuss the importance of K2-280b for testing formation scenarios of sub-Saturn planets and the current sample of this intriguing group of planets that are absent in the Solar System

TOI-2266 b : a keystone super-Earth at the edge of the M dwarf radius valley

We validate the Transiting Exoplanet Survey Satellite (TESS) object of interest TOI-2266.01 (TIC 348911) as a small transiting planet (most likely a super-Earth) orbiting a faint M5 dwarf (V=16.54) on a 2.33~d orbit. The validation is based on an approach where multicolour transit light curves are used to robustly estimate the upper limit of the transiting object's radius. Our analysis uses SPOC-pipeline TESS light curves from Sectors 24, 25, 51, and 52, simultaneous multicolour transit photometry observed with MuSCAT2, MuSCAT3, and HiPERCAM, and additional transit photometry observed with the LCOGT telescopes. TOI-2266 b is found to be a planet with a radius of 1.54 ± 0.09,R⊕, which locates it at the edge of the transition zone between rocky planets, water-rich planets, and sub-Neptunes (the so-called M~dwarf radius valley). The planet is amenable to ground-based radial velocity mass measurement with red-sensitive spectrographs installed in large telescopes, such as MAROON-X and Keck Planet Finder (KPF), which makes it a valuable addition to a relatively small population of planets that can be used to probe the physics of the transition zone. Further, the planet's orbital period of 2.33 days places it inside a 'keystone planet' wedge in the period-radius plane where competing planet formation scenarios make conflicting predictions on how the radius valley depends on the orbital period. This makes the planet also a welcome addition to the small population of planets that can be used to test small-planet formation scenarios around M~dwarfs.Peer reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London