bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis of impaired extraocular muscle function in a mouse model of congenital myopathy due to compound heterozygous Ryr1 mutations
Authors: Eckhardt Jan , Bachmann Christoph , Benucci Sofia , Elbaz Moran , Ruiz Alexis , Zorzato Francesco , Treves Susan 
Published: March 2020

AbstractMutations in the RYR1 gene are the most common cause of human congenital myopathies, and patients with recessive mutations are severely affected and often display ptosis and/or ophthalmoplegia. In order to gain insight into the mechanism leading to extraocular muscle (EOM) involvement, we investigated the biochemical, structural and physiological properties of eye muscles from mouse models we created knocked-in for Ryr1 mutations. Ex vivo force production in EOMs from compound heterozygous RyR1p.Q1970fsX16+p.A4329D mutant mice was significantly reduced compared with that observed in wild-type, single heterozygous mutant carriers or homozygous RyR1p.A4329D mice. The decrease in muscle force was also accompanied by approximately a 40% reduction in RyR1 protein content, a decrease in electrically evoked calcium transients, disorganization of the muscle ultrastructure and a decrease in the number of calcium release units. Unexpectedly, the superfast and ocular-muscle-specific myosin heavy chain-EO isoform was almost undetectable in RyR1p.Q1970fsX16+p.A4329D mutant mice.The results of this study show for the first time that the EOM phenotype caused by the RyR1p.Q1970fsX16+p.A4329D compound heterozygous Ryr1 mutations is complex and due to a combination of modifications including a direct effect on the macromolecular complex involved in calcium release and indirect effects on the expression of myosin heavy chain isoforms.
Drone imagery in Islamic State propaganda: flying like a state
Authors: Archambault Emil , Veilleux-Lepage Yannick 
Published: March 2020

Abstract
This article provides a comprehensive analysis of the Islamic State's use of images taken by drones, drawing on a dataset of ISIS propaganda images from October 2016 to December 2018. Analysing the three principal uses of drone imagery by ISIS—images of drone strikes, images of other attacks and observation—we argue that ISIS's use of drones distinguishes itself from other state and non-state uses of drones primarily by its communicative and symbolic value. While ISIS’ use of drone strikes takes place in a tactical rather than strategic setting, its employment of drones to film VBIED attacks allows them to achieve a strategic effect. After outlining ISIS’ use of drones for combat air support and to film ground (particularly VBIED) attacks, we argue, drawing on political geography, that ISIS employs drones in propaganda to stake and reinforce a claim to sovereign control of territory, performed through the flying of aircraft. The use of drone imagery, we argue, taps into long-standing visual and discursive strategies which associate vertical hierarchy and flying with mastery and control, allowing ISIS to display attributes of aerial sovereignty. This article, through an analysis of ISIS drone propaganda, provides a rare insight into non-state actors’ perception of drones and the communicative value of drone images, in addition to suggesting further avenues for the incorporation of political–geographical studies of verticality into the study of political violence and rhetoric.
Optimizing Immunization Strategies in Patients with IBD
Authors: Caldera Freddy , Ley Dana , Hayney Mary S , Farraye Francis A 
Published: March 2020

Abstract
Recent advances in the treatment of inflammatory bowel disease (IBD) include the use of immune modifiers and monoclonal antibodies, such as tumor necrosis factor (TNF) alpha inhibitors, anti-integrin agents, janus kinase inhibitors, and interleukin-12/23 inhibitors. These agents achieve higher rates of clinical remission and mucosal healing than conventional therapy. However, these therapies increase the risk of infections, including some vaccine-preventable diseases. Infections are one of the most common adverse event of immunosuppressive therapy. Thus, providers should optimize immunization strategies to reduce the risk of vaccine-preventable infections in patients with IBD. There are several newly licensed vaccines recommended for adults by the US Advisory Committee on Immunization Practices. This review will focus on how gastroenterology providers can implement the adult immunization schedule approved by ACIP for patients with IBD.
Blood and Lymph Node Dissemination of Clonal Genome-Intact Human Immunodeficiency Virus 1 DNA Sequences During Suppressive Antiretroviral Therapy
Authors: Kuo Hsiao-Hsuan , Banga Riddhima , Lee Guinevere Q , Gao Ce , Cavassini Matthias , Corpataux Jean-Marc , Blackmer Jane E , zur Wiesch Schulze , Yu Xu G , Pantaleo Giuseppe , Perreau Matthieu , Lichterfeld Mathias 
Published: March 2020

Abstract
The majority of cells with latent human immunodeficiency virus 1 infection are located in lymphoid tissues that are difficult to access. In the current study, we used single-genome near-full-length proviral sequencing to evaluate intact and defective proviruses in blood and lymph node CD4 T cells enriched for specific functional polarizations. We observed minor variations between the frequencies of proviral sequences within individual CD4 T-cell subsets and across tissue compartments. However, we noted multiple clonal clusters of identical intact or defective proviral sequences from distinct compartments and CD4 T-cell subpopulations, suggesting frequent interchanges between viral reservoir cells in blood and tissues.
Why is the Mass Public Not More Supportive of Free Trade? Evidence from the United States
Authors: Bearce David H , Moya Samantha L 
Published: March 2020

AbstractThis article explores why citizens favor protection despite the economic case for free trade. It argues that due to a lack of training and in an environment of stable prices, many individuals are not aware of the consumption benefits. Even when they are aware, citizens tend to discount these benefits due to media coverage of the employment costs and loss aversion. The article presents survey evidence from an American sample, showing that a belief in lost jobs is more strongly associated with trade preferences than a belief in lower prices. Given that the former pushes citizens toward less favorable trade attitudes, it also presents evidence from a priming experiment, testing if attitudes can be moved in a more favorable direction with positive information. Factual information about the consumer benefits has no effect, but information about the employment effects shifts attitudes positively. In the present environment, it thus appears more effective to prime pro-trade attitudes by appealing to jobs than to prices.
Role of low-level quinolone resistance in generating tolerance in Escherichia coli under therapeutic concentrations of ciprofloxacin
Authors: Ortiz-Padilla M , Diaz-Diaz S , Machuca J , Tejada-Gonzalez A , Recacha E , Docobo-Pérez F , Pascual A , Rodríguez-Martínez J M 
Published: March 2020

Abstract

Background
Tolerance (including persistence) and resistance result in increased survival under antibiotic pressure.

Objectives
We evaluated the interplay between resistance and tolerance to ciprofloxacin under therapeutic and killing conditions to determine the contribution of low-level quinolone resistance (LLQR) mechanisms to tolerance. We also determined how the interaction between resistance (LLQR phenotypes) and tolerance was modified under SOS response suppression.

Methods
Twelve isogenic Escherichia coli strains harbouring quinolone resistance mechanisms combined with SOS response deficiency and six clinical E. coli isolates (LLQR or non-LLQR) were evaluated. Survival (tolerance or persistence) assays were used to measure surviving bacteria after a short period (up to 4 h) of bactericidal antibiotic treatment under therapeutic and killing concentrations of ciprofloxacin [1 mg/L, EUCAST/CLSI breakpoint for resistance; and 2.5 mg/L, peak serum concentration (Cmax) of this drug].

Results
QRDR substitutions (S83L in GyrA alone or combined with S80R in ParC) significantly increased the fraction of tolerant bacteria (2–4 log10 cfu/mL) after exposure to ciprofloxacin at clinically relevant concentrations. The impact on tolerant bacteria due to SOS response suppression (including persistence mediated by the tisB gene) was reversed by LLQR mechanisms at therapeutic concentrations. Furthermore, no reduction in the fraction of tolerant bacteria due to SOS response suppression was observed when S83L in GyrA plus S80R in ParC were combined.

Conclusions
Tolerance and quinolone resistance mutations interact synergistically, giving LLQR mechanisms an additional role in allowing bacterial survival and evasion of therapeutic antimicrobial conditions by a combination of the two strategies. At clinically relevant concentrations, LLQR mechanisms reverse further impact of SOS response suppression in reducing bacterial tolerance.
Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease
Authors: Avataneo Valeria , de Nicolò Amedeo , Cusato Jessica , Antonucci Miriam , Manca Alessandra , Palermiti Alice , Waitt Catriona , Walimbwa Stephen , Lamorde Mohammed , di Perri Giovanni , D’Avolio Antonio 
Published: March 2020

Abstract

Background
Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification.

Objectives
The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma.

Methods
Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 μm, 2.1 × 50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines.

Results
Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety.

Conclusions
This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak.
Screening of OXA-244 producers, a difficult-to-detect and emerging OXA-48 variant?
Authors: Emeraud Cecile , Biez Laura , Girlich Delphine , Jousset Agnès B , Naas Thierry , Bonnin Rémy A , Dortet Laurent 
Published: March 2020

Abstract

Background
OXA-244, a single amino acid variant of OXA-48, demonstrates weaker hydrolytic activity towards carbapenems and temocillin compared with OXA-48. Of note, these antimicrobials are present in high concentrations in several carbapenemase-producing Enterobacterales (CPE) screening media. As a result, some screening media fail to grow OXA-244-producing isolates, while the prevalence of OXA-244 producers is constantly increasing in France.

Methods
Here, we evaluate the performance of three commercially available CPE screening media [ChromID® CARBA SMART (bioMérieux), Brilliance™ CRE (Thermo Fisher) and mSuperCARBA™ (MAST Diagnostic)] for their ability to detect OXA-244 producers (n = 101). As OXA-244 producers may also express an ESBL, two additional ESBL screening media were tested (Brilliance™ ESBL and ChromID® BLSE). MICs of temocillin and imipenem were determined by broth microdilution. The clonality of OXA-244-producing Escherichia coli isolates (n = 97) was assessed by MLST.

Results
Overall, the sensitivity of the ChromID® CARBA SMART, Brilliance™ CRE and mSuperCARBA™ media were 14% (95% CI = 8.1%–22.5%), 54% (95% CI = 43.3%–63.4%) and 99% (95% CI = 93.8%–100%), respectively, for the detection of OXA-244 producers. Among the 101 OXA-244-producing isolates, 96% were E. coli and 77%–78% grew on ESBL screening media. MLST analysis identified five main STs among OXA-244-producing E. coli isolates: ST38 (n = 37), ST361 (n = 17), ST69 (n = 12), ST167 (n = 11) and ST10 (n = 8).

Conclusions
Our results demonstrated that the mSuperCARBA™ medium is very efficient in the detection of OXA-244 producers, unlike the ChromID® CARBA SMART medium. The high prevalence of ESBLs among OXA-244 producers allowed detection of 77%–78% of them using ESBL-specific screening media.
Gene disruption of medaka (Oryzias latipes) orthologue for mammalian tissue-type transglutaminase (TG2) causes movement retardation
Authors: Watanabe Yuko , Okuya Kazuho , Takada Yuki , Kinoshita Masato , Yokoi Saori , Chisada Shinichi , Kamei Yasuhiro , Tatsukawa Hideki , Yamamoto Naoyuki , Abe Hideki , Hashimoto Hisashi , Hitomi Kiyotaka 
Published: March 2020

Abstract
Transglutaminases are an enzyme family that catalyses protein cross-linking essential for several biological functions. In the previous studies, we characterized the orthologues of the mammalian transglutaminase family in medaka (Oryzias latipes), an established fish model. Among the human isozymes, tissue-type transglutaminase (TG2) has multiple functions that are involved in several biological phenomena. In this study, we established medaka mutants deficient for the orthologue of human TG2 using the CRISPR/Cas9 and transcription activator-like effector nucleases systems. Although apparent morphological changes in the phenotype were not observed, movement retardation was found in the mutant fish when evaluated by a tank-diving test. Furthermore, comparative immunohistochemistry analysis using in this fish model revealed that orthologue of human TG2 was expressed at the periventricular layer of the optic tectum. Our findings provide novel insight for the relationship between tissue-type transglutaminase and the nervous system and the associated behaviour.
Make It Hot? How Food Temperature (Mis)Guides Product Judgments
Authors: Yamim Amanda P , Mai Robert , Werle Carolina O C 
Published: March 2020

AbstractDespite being a basic food property, food temperature has been largely neglected by consumer research thus far. This research proposes that consumers spontaneously infer that warm foods contain more calories, an unexplored lay belief we named the “warm is calorie-rich” intuition. Eight studies reveal that this deep-seated intuition has powerful implications in terms of guiding (and often biasing) product judgments and consumption decisions. Temperature-induced calorie inferences are rooted in perceptions that warm foods are more filling and tastier than cold ones, which enhance warm foods’ desirability and affect consumer choices. The preference for warm products is mitigated when food energy does not provide utility to consumers though, such as when consumers have a health goal active, and it reverses when consumers purposefully aim to reduce their calorie intake. The “warm is calorie-rich” intuition is important for marketers and managers because warm food temperatures can increase willingness to pay (by 25%) and amount served (+27%), as well as influence consumer preferences. This intuition also has important public policy implications: consumers tend to underestimate the nutritional value of cold foods, resulting in increased consumption of calories (+31%) and fat (+37%).
Heparan Sulfate Proteoglycans Undergo Differential Expression Alterations in Alzheimer Disease Brains
Authors: Lorente-Gea Laura , García Beatriz , Martín Carla , Ordiales Helena , García-Suárez Olivia , Piña-Batista Kelvin M , Merayo-Lloves Jesús , Quirós Luís M , Fernández-Vega Iván 
Published: March 2020

Abstract
Previous studies have reported that heparan sulfate proteoglycans (HSPGs) promote amyloid-beta peptide and tau fibrillization in Alzheimer disease (AD) and provide resistance against proteolytic breakdown. We compared the expression levels of 17 HSPG core proteins in 18 AD cases and 6 controls. RT-PCR was used to analyze transcription levels. Immunohistochemistry was performed to localize HSPGs in the brain tissue. We detected expression of all HSPG genes investigated. SDC1, GPC3, and CD44v3 showed the lowest levels of expression, while SDC3 and GPC1 showed the highest. Remarkably, SDC4 and SRGN were overexpressed in most of the areas analyzed. Immunohistochemistry revealed the presence of both SDC4 and SRGN mostly associated with tau and amyloid-β pathology throughout the AD brains. In conclusion, in view of the involvement of HSPGs in AD pathology, especially SDC4 and SRGN, there would seem to be a relationship between the regulation of core protein expression and the pathological features suggesting HSPGs are potential inducers of the disease.
Identification of client iron–sulfur proteins of the chloroplastic NFU2 transfer protein in Arabidopsis thaliana
Authors: Berger Nathalie , Vignols Florence , Przybyla-Toscano Jonathan , Roland Mélanie , Rofidal Valérie , Touraine Brigitte , Zienkiewicz Krzysztof , Couturier Jérémy , Feussner Ivo , Santoni Véronique , Rouhier Nicolas , Gaymard Frédéric , Dubos Christian 
Published: March 2020

Abstract
Iron–sulfur (Fe-S) proteins have critical functions in plastids, notably participating in photosynthetic electron transfer, sulfur and nitrogen assimilation, chlorophyll metabolism, and vitamin or amino acid biosynthesis. Their maturation relies on the so-called SUF (sulfur mobilization) assembly machinery. Fe-S clusters are synthesized de novo on a scaffold protein complex and then delivered to client proteins via several transfer proteins. However, the maturation pathways of most client proteins and their specificities for transfer proteins are mostly unknown. In order to decipher the proteins interacting with the Fe-S cluster transfer protein NFU2, one of the three plastidial representatives found in Arabidopsis thaliana, we performed a quantitative proteomic analysis of shoots, roots, and seedlings of nfu2 plants, combined with NFU2 co-immunoprecipitation and binary yeast two-hybrid experiments. We identified 14 new targets, among which nine were validated in planta using a binary bimolecular fluorescence complementation assay. These analyses also revealed a possible role for NFU2 in the plant response to desiccation. Altogether, this study better delineates the maturation pathways of many chloroplast Fe-S proteins, considerably extending the number of NFU2 clients. It also helps to clarify the respective roles of the three NFU paralogs NFU1, NFU2, and NFU3.
Massive discs around low-mass stars
Authors: Haworth Thomas J , Cadman James , Meru Farzana , Hall Cassandra , Albertini Emma , Forgan Duncan , Rice Ken , Owen James E 
Published: March 2020

ABSTRACT
We use a suite of smoothed particle hydrodynamic simulations to investigate the susceptibility of protoplanetary discs to the effects of self-gravity as a function of star–disc properties. We also include passive irradiation from the host star using different models for the stellar luminosities. The critical disc-to-star mass ratio for axisymmetry (for which we produce criteria) increases significantly for low-mass stars. This could have important consequences for increasing the potential mass reservoir in a proto Trappist-1 system, since even the efficient Ormel et al. formation model will be influenced by processes like external photoevaporation, which can rapidly and dramatically deplete the dust reservoir. The aforementioned scaling of the critical Md/M* for axisymmetry occurs in part because the Toomre Q parameter has a linear dependence on surface density (which promotes instability) and only an $M_*^{1/2}$ dependence on shear (which reduces instability), but also occurs because, for a given Md/M*, the thermal evolution depends on the host star mass. The early phase stellar irradiation of the disc (for which the luminosity is much higher than at the zero age main sequence, particularly at low stellar masses) can also play a key role in significantly reducing the role of self-gravity, meaning that even solar mass stars could support axisymmetric discs a factor two higher in mass than usually considered possible. We apply our criteria to the DSHARP discs with spirals, finding that self-gravity can explain the observed spirals so long as the discs are optically thick to the host star irradiation.
Euclid: the selection of quiescent and star-forming galaxies using observed colours
Authors: Bisigello L , Kuchner U , Conselice C J , Andreon S , Bolzonella M , Duc P-A , Garilli B , Humphrey A , Maraston C , Moresco M , Pozzetti L , Tortora C , Zamorani G , Auricchio N , Brinchmann J , Capobianco V , Carretero J , Castander F J , Castellano M , Cavuoti S , Cimatti A , Cledassou R , Congedo G , Conversi L , Corcione L , Cropper M S , Dusini S , Frailis M , Franceschi E , Franzetti P , Fumana M , Hormuth F , Israel H , Jahnke K , Kermiche S , Kitching T , Kohley R , Kubik B , Kunz M , Le Fèvre O , Ligori S , Lilje P B , Lloro I , Maiorano E , Marggraf O , Massey R , Masters D C , Mei S , Mellier Y , Meylan G , Padilla C , Paltani S , Pasian F , Pettorino V , Pires S , Polenta G , Poncet M , Raison F , Rhodes J , Roncarelli M , Rossetti E , Saglia R , Sauvage M , Schneider P , Secroun A , Serrano S , Sureau F , Taylor A N , Tereno I , Toledo-Moreo R , Valenziano L , Wang Y , Wetzstein M , Zoubian J 
Published: March 2020

ABSTRACT
The Euclid mission will observe well over a billion galaxies out to z ∼ 6 and beyond. This will offer an unrivalled opportunity to investigate several key questions for understanding galaxy formation and evolution. The first step for many of these studies will be the selection of a sample of quiescent and star-forming galaxies, as is often done in the literature by using well-known colour techniques such as the ‘UVJ’ diagram. However, given the limited number of filters available for the Euclid telescope, the recovery of such rest-frame colours will be challenging. We therefore investigate the use of observed Euclid colours, on their own and together with ground-based u-band observations, for selecting quiescent and star-forming galaxies. The most efficient colour combination, among the ones tested in this work, consists of the (u − VIS) and (VIS − J) colours. We find that this combination allows users to select a sample of quiescent galaxies complete to above $\sim 70{{\ \rm per\ cent}}$ and with less than 15${{\ \rm per\ cent}}$ contamination at redshifts in the range 0.75 &lt; z &lt; 1. For galaxies at high-z or without the u-band complementary observations, the (VIS − Y) and (J − H) colours represent a valid alternative, with $\gt 65{{\ \rm per\ cent}}$ completeness level and contamination below 20${{\ \rm per\ cent}}$ at 1 &lt; z &lt; 2 for finding quiescent galaxies. In comparison, the sample of quiescent galaxies selected with the traditional UVJ technique is only $\sim 20{{\ \rm per\ cent}}$ complete at z &lt; 3, when recovering the rest-frame colours using mock Euclid observations. This shows that our new methodology is the most suitable one when only Euclid bands, along with u-band imaging, are available.