bluuebunny/crossref_metadata_2025 huggingface dataset:
A theoretical scenario for Galactic RR Lyrae in the Gaia data base: constraints on the parallax offset
Authors: Marconi M , Molinaro R , Ripepi V , Leccia S , Musella I , De Somma G , Gatto M , Moretti M I
Published: November 2020

On the basis of an extended set of non-linear convective RR Lyrae pulsation models we derive the first theoretical light curves in the Gaia bands G, GBP, and GRP and the corresponding intensity-weighted mean magnitudes and pulsation amplitudes. The effects of chemical composition on the derived Bailey diagrams in the Gaia filters are discussed for both Fundamental and first overtone mode pulsators. The inferred mean magnitudes and colours are used to derive the first theoretical Period–Wesenheit relations for RR Lyrae in the Gaia filters. The application of the theoretical Period–Wesenheit relations for both the Fundamental and first overtone mode to Galactic RR Lyrae in the Gaia Data Release 2 data base and complementary information on individual metal abundances allows us to derive theoretical estimates of their individual parallaxes. These results are compared with the astrometric solutions to conclude that a very small offset, consistent with zero, is required in order to reconcile the predicted distances with Gaia results.
Turbulent density and pressure fluctuations in the stratified intracluster medium
Authors: Mohapatra Rajsekhar , Federrath Christoph , Sharma Prateek
Published: November 2020

Turbulent gas motions are observed in the intracluster medium (ICM). The ICM is density-stratified, with the gas density being highest at the centre of the cluster and decreasing radially outwards. As a result of this, Kolmogorov (homogeneous, isotropic) turbulence theory does not apply to the ICM. The gas motions are instead explained by anisotropic stratified turbulence, with the stratification quantified by the perpendicular Froude number (Fr⊥). These turbulent motions are associated with density and pressure fluctuations, which manifest as perturbations in X-ray surface brightness maps of the ICM and as thermal Sunyaev–Zeldovich effect (SZ) fluctuations, respectively. In order to advance our understanding of the relations between these fluctuations and the turbulent gas velocities, we have conducted 100 high-resolution hydrodynamic simulations of stratified turbulence (2562 × 384–10242 × 1536 resolution elements), in which we scan the parameter space of subsonic rms Mach number ($\mathcal {M}$), Fr⊥, and the ratio of entropy and pressure scale heights (RPS = HP/HS), relevant to the ICM. We develop a new scaling relation between the standard deviation of logarithmic density fluctuations (σs, where s = ln (ρ/$\langle$ρ$\rangle$)), $\mathcal {M}$, and Fr⊥, which covers both the strongly stratified (Fr⊥ ≪ 1) and weakly stratified (Fr⊥ ≫ 1) turbulence regimes: $\sigma _{\rm s}^2=\ln (1+b^2\mathcal {M}^4+0.10/(\mathrm{Fr}_\perp +0.25/\sqrt{\mathrm{Fr}_\perp })^2\mathcal {M}^2R_{\rm PS})$, where b ∼ 1/3 for solenoidal turbulence driving studied here. We further find that logarithmic pressure fluctuations σ(ln P/ < P >) are independent of stratification and scale according to the relation $\sigma _{(\ln {\bar{P}})}^2=\ln (1+b^2\gamma ^2\mathcal {M}^4)$, where $\bar{P}=P/\left\langle P \right\rangle $ and γ is the adiabatic index of the gas. We have tested these scaling relations to be valid over the parameter ranges $\mathcal {M} = 0.01$–0.40, Fr⊥ = 0.04–10.0, and RPS = 0.33–2.33.
Orbital evolution of Mars-crossing asteroids
Authors: Wlodarczyk I
Published: November 2020

This study is an orbital analysis of the interesting Mars-crossing asteroids (MCAs), also known as Mars-crosser (MC) asteroids or Mars-crossers (MCs). We computed that after 100 million years (Myr), approximately 66 ${{\ \rm per\ cent}}$ of all known MCs are ejected out of the Solar System by collision with the Sun, the planets, Ceres, Pallas, Vesta, or Hygiea. The rate of MC migration is high. Thus, this population of MCs would be supplied by just as many asteroids from outside the Solar System. We estimated the rate at which near-Earth objects were created from MCs throughout a 100 Myr period, with Atiras accounting for nearly 3 ${{\ \rm per\ cent}}$ of these objects, over 2 ${{\ \rm per\ cent}}$ were Atens, nearly 7.5 ${{\ \rm per\ cent}}$ were Apollos, approximately 9${{\ \rm per\ cent}}$ were Amors, and nearly 0.4 ${{\ \rm per\ cent}}$ became Centaurs. These results were calculated with 10 000 yr output intervals. Furthermore, 0.028${{\ \rm per\ cent}}$ of all the starting MCs were in retrograde orbits for at least 10 000 yr. We found that majority of the remaining MCs have migrated into the region of three asteroid families: Phocaea, Hungaria, and Flora. We calculated a small but significant influence of Ceres, Pallas, Vesta, and Hygiea on the orbital evolution of the MCs. From the AstDys catalogue, we found that the largest number of studied numbered MCs have their Lyapunov time (LT) in the range 2–4 kyr. Using the orbfit software, we computed the LT of selected MCs in retrograde orbits, and obtained an LT of between 540 yr (asteroid 2016 DR1) and 71 000 yr (asteroid 42887 1999 RV155).
Resolving period aliases for TESS monotransits recovered during the extended mission
Authors: Cooke Benjamin F , Pollacco Don , Anderson David R , Bayliss Daniel , Bouchy François , Gill Samuel , Grieves Nolan , Lendl Monika , Nielsen Louise D , Udry Stéphane , Wheatley Peter J
Published: November 2020

We set out to explore how best to mitigate the number of period aliases for a transiting Transiting Exoplanet Survey Satellite (TESS) system with two identified transits separated by a large time period on the order of years. We simulate a realistic population of doubly transiting planets based on the observing strategy of the TESS primary and extended missions. We next simulate additional observations using photometry (NGTS) and spectroscopy (HARPS and CORALIE) and assess its impact on the period aliases of systems with two TESS transits. We find that TESS will detect around 400 exoplanets that exhibit one transit in each of the primary and extended missions. Based on the temporal coverage, each of these systems will have an average of 38 period aliases. We find that, assuming a combination of NGTS and CORALIE over observing campaigns spanning 50 d, we can find the true alias, and thus solve the period, for up to 207 of these systems with even more being solved if the observing campaigns are extended or we upgrade to HARPS over CORALIE.
Asteroseismology of the DAV star R808
Authors: Chen Y H , Shu H
Published: November 2020

The DAV star R808 was observed by 13 different telescopes for more than 170 h in 2009 April on the WET run XCOV26. 25 independent pulsation frequencies were identified by this data set. We assumed 19 m = 0 modes and performed an asteroseismological study on those 19 modes. We evolve grids of DAV star models by wdec adopting the element diffusion scheme with pure and screened Coulomb potential effect. The core compositions are from white dwarf models evolved by mesa, which are thermal nuclear burning results. Our best-fitting model is from the screened Coulomb potential scenario, which has parameters of log(MHe/M*) = −2.4, log(MH/M*) = −5.2, Teff = 11100 K, M* = 0.710 M⊙, logg = 8.194, and σRMS = 2.86 s. The value of σRMS is the smallest among the four existing asteroseismological work. The average period spacing is 46.299 s for l = 1 modes and 25.647 s for l = 2 modes. The other six observed modes can be fitted by $m\, \ne$ 0 components of some modes for our best-fitting model. Fitting the 25 observed modes, we obtain a σRMS value of 2.59 s. Considering the period spacings, we also assume, that at least in one case, we detect an l = 2 trapped mode.
‘Ears’ formation in supernova remnants: overhearing an interaction history with bipolar circumstellar structures
Authors: Chiotellis A , Boumis P , Spetsieri Z T
Published: November 2020

A characteristic feature that is frequently found in nearby supernova remnants (SNRs) is the existence of two antisymmetric, local protrusions that are projected as two ‘ears’ in the morphology of the nebula. In this paper, we present a novel scenario for the ‘ear’ formation process, according to which the two lobes are formed through the interaction of the SNR with a bipolar circumstellar medium (CSM) that was surrounding the explosion’s centre. We conduct two-dimensional hydrodynamic simulations and we show that the SNR shock breakout from the bipolar CSM triggers the inflation of two opposite protrusions at the equator of the remnant, which retain their size and shape from several hundreds up to a few thousand years of the SNR evolution. We run a set of models by varying the supernova (SN) and CSM properties and we demonstrate that the extracted results reveal good agreement with the observables, regarding the sizes, lifespan, morphology and kinematics of the ‘ears’. We discuss the plausibility of our model in nature and we suggest that the most likely progenitors of the ‘ear-carrying’ SNRs are the luminous blue variables or the red/yellow supergiants for the SNRs resulting from core collapse SN events, and the symbiotic binaries or the planetary nebulae for the SNRs formed by Type Ia SNe. Finally, we compare our model with other ‘ear’ formation models found in the literature and we show that there are distinctive differences among them, concerning the orientation of the ‘ears’ and the phase in which the ‘ear’ formation process occurs.
LOFAR detection of a low-power radio halo in the galaxy cluster Abell 990
Authors: Hoang D N , Shimwell T W , Osinga E , Bonafede A , Brüggen M , Botteon A , Brunetti G , Cassano R , Cuciti V , Drabent A , Jones C , Röttgering H J A , van Weeren R J
Published: November 2020

Radio haloes are extended (∼Mpc), steep spectrum sources found in the central region of dynamically disturbed clusters of galaxies. Only a handful of radio haloes have been reported to reside in galaxy clusters with a mass $M_{500}\lesssim 5\times 10^{14}\, \mathrm{ M}_\odot$. In this paper, we present a LOw Frequency ARray (LOFAR) 144 MHz detection of a radio halo in the galaxy cluster Abell 990 with a mass of $M_{500}=(4.9\pm 0.3)\times 10^{14}\, \mathrm{ M}_\odot$. The halo has a projected size of ${\sim} 700\, {\rm kpc}$ and a flux density of $20.2\pm 2.2\, {\rm mJy}$ or a radio power of $1.2\pm 0.1\times 10^{24}\, {\rm W\, Hz}^{-1}$ at the cluster redshift (z = 0.144) that makes it one of the two haloes with the lowest radio power detected to date. Our analysis of the emission from the cluster with Chandra archival data using dynamical indicators shows that the cluster is not undergoing a major merger but is a slightly disturbed system with a mean temperature of $5\, {\rm keV}$. The low X-ray luminosity of $L_{\mathrm{ X}}=(3.66\pm 0.08)\times 10^{44}\, {\rm erg\, s}^{-1}$ in the 0.1–2.4 keV band implies that the cluster is one of the least luminous systems known to host a radio halo. Our detection of the radio halo in Abell 990 opens the possibility of detecting many more haloes in poorly explored less massive clusters with low-frequency telescopes such as LOFAR, Murchison Widefield Array (MWA, Phase II), and upgraded Giant Metrewave Radio Telescope (uGMRT).
Reconstitution of mammalian mitochondrial translation system capable of correct initiation and long polypeptide synthesis from leaderless mRNA
Authors: Lee Muhoon , Matsunaga Noriko , Akabane Shiori , Yasuda Ippei , Ueda Takuya , Takeuchi-Tomita Nono
Published: November 2020

Mammalian mitochondria have their own dedicated protein synthesis system, which produces 13 essential subunits of the oxidative phosphorylation complexes. We have reconstituted an in vitro translation system from mammalian mitochondria, utilizing purified recombinant mitochondrial translation factors, 55S ribosomes from pig liver mitochondria, and a tRNA mixture from either Escherichia coli or yeast. The system is capable of translating leaderless mRNAs encoding model proteins (DHFR and nanoLuciferase) or some mtDNA-encoded proteins. We show that a leaderless mRNA, encoding nanoLuciferase, is faithfully initiated without the need for any auxiliary factors other than IF-2mt and IF-3mt. We found that the ribosome-dependent GTPase activities of both the translocase EF-G1mt and the recycling factor EF-G2mt are insensitive to fusidic acid (FA), the translation inhibitor that targets bacterial EF-G homologs, and consequently the system is resistant to FA. Moreover, we demonstrate that a polyproline sequence in the protein causes 55S mitochondrial ribosome stalling, yielding ribosome nascent chain complexes. Analyses of the effects of the Mg concentration on the polyproline-mediated ribosome stalling suggested the unique regulation of peptide elongation by the mitoribosome. This system will be useful for analyzing the mechanism of translation initiation, and the interactions between the nascent peptide chain and the mitochondrial ribosome.
An Evaluation of Potential Unintended Consequences of a Nicotine Product Standard: A Focus on Drinking History and Outcomes
Authors: Dermody Sarah S , Tessier Katelyn M , Meier Ellen , al’Absi Mustafa , Denlinger-Apte Rachel L , Drobes David J , Jensen Joni , Koopmeiners Joseph S , Pacek Lauren R , Tidey Jennifer W , Vandrey Ryan , Donny Eric , Hatsukami Dorothy
Published: November 2020

Introduction

A nicotine product standard reducing the nicotine content in cigarettes could improve public health by reducing smoking. This study evaluated the potential unintended consequences of a reduced nicotine product standard by examining its effects on (1) smoking behaviors based on drinking history; (2) drinking behavior; and (3) daily associations between smoking and drinking.

Methods

Adults who smoke daily (n = 752) in the United States were randomly assigned to smoke very low nicotine content (VLNC) cigarettes versus normal nicotine content (NNC; control) cigarettes for 20 weeks. Linear mixed models determined if baseline drinking moderated the effects of VLNC versus NNC cigarettes on Week 20 smoking outcomes. Time-varying effect models estimated the daily association between smoking VLNC cigarettes and drinking outcomes.

Results

Higher baseline alcohol use (vs no use or lower use) was associated with a smaller effect of VLNC on Week 20 urinary total nicotine equivalents (ps < .05). No additional moderation was supported (ps > .05). In the subsample who drank (n = 415), in the VLNC versus NNC condition, daily alcohol use was significantly reduced from Weeks 17 to 20 and odds of binge drinking were significantly reduced from Weeks 9 to 17. By Week 7, in the VLNC cigarette condition (n = 272), smoking no longer predicted alcohol use but remained associated with binge drinking.

Conclusions

We did not support negative unintended consequences of a nicotine product standard. Nicotine reduction in cigarettes generally affected smoking behavior for individuals who do not drink or drink light-to-moderate amounts in similar ways. Extended VLNC cigarette use may improve public health by reducing drinking behavior.

Implications

There was no evidence that a VLNC product standard would result in unintended consequences based on drinking history or when considering alcohol outcomes. Specifically, we found that a very low nicotine standard in cigarettes generally reduces smoking outcomes for those who do not drink and those who drink light-to-moderate amounts. Furthermore, an added public health benefit of a very low nicotine standard for cigarettes could be a reduction in alcohol use and binge drinking over time. Finally, smoking VLNC cigarettes may result in a decoupling of the daily associations between smoking and drinking.
Evaluating HIV Viral Rebound Among Persons on Suppressive Antiretroviral Treatment in the Era of “Undetectable Equals Untransmittable (U = U)”
Authors: Min Sugi , Gillani Fizza S , Aung Su , Garland Joseph M , Beckwith Curt G
Published: November 2020

Background

Studies have demonstrated that persons with HIV (PWH) maintaining viral suppression do not transmit HIV to HIV-negative partners through condomless sex, leading to the “Undetectable = Untransmittable (U = U)” prevention campaign. However, few studies have examined the durability of suppression in the era of U = U.

Methods

This retrospective cohort study was conducted in Providence, Rhode Island. PWH aged ≥18 years with documented viral suppression (defined as at least 1 viral load [VL] <200 copies/mL and no VL ≥200 copies/mL) in 2015 were included in the baseline cohort. Primary outcomes were viral suppression, viral rebound (at least 1 VL ≥200 copies/mL), or gap in VL monitoring assessed annually from 2016 to 2019. Those with viral rebound were assessed for resuppression within 6 months. Demographic and clinical characteristics associated with viral rebound or gaps in VL monitoring were investigated by bivariate analysis and logistic regression.

Results

A total of 1242 patients with viral suppression were included in the baseline cohort. In each follow-up year, 85%–90% maintained viral suppression, 2%–5% experienced viral rebound, and 8%–10% had a gap in VL monitoring. Among those with viral rebound, approximately one-half were suppressed again within 6 months. In the logistic regression models, retention in care was significantly associated with viral suppression, while younger age, black race, high school or equivalent education, non–men who have sex with men, and history of incarceration were significantly associated with viral rebound.

Conclusions

In the U = U era, most patients with viral suppression who are retained in care are likely to maintain viral suppression over time. Some patients require additional support for regular VL monitoring.
Regional integration and income inequality: a synthetic counterfactual analysis of the European Monetary Union
Authors: Bouvet Florence
Published: November 2020

In Europe, it is quite common for public opinions and national politicians to blame economic insecurity and rising inequality on deeper regional integration within the European Union (EU), and especially on the euro. There is, however, no empirical research that clearly identifies the euro as the cause of the recent increase in income inequality. Using the synthetic counterfactual methodology developed by Abadie and Gardeazabal (2003), I estimate what would have happened to inequality in both gross and net income within euro-area countries, had these countries not switched to the single currency. In most countries (especially peripheral countries), without the euro, gross-income inequality would have been lower, while net-income inequality would have been higher. These results imply that, while deeper economic integration might have exacerbated gross income inequality, lower interest rates allowed countries to counteract these disparities with their social welfare programmes.
Household Portfolio Underdiversification and Probability Weighting: Evidence from the Field
Authors: Dimmock Stephen G , Kouwenberg Roy , Mitchell Olivia S , Peijnenburg Kim
Published: November 2020

We test whether probability weighting affects household portfolio choice in a representative survey. On average, people display inverse-S-shaped probability weighting, overweighting low probability events. As theory predicts, probability weighting is positively associated with portfolio underdiversification and significant Sharpe ratio losses. Analyzing respondents’ individual stock holdings, we find higher probability weighting is associated with owning lottery-type stocks and positively skewed equity portfolios. People with higher probability weighting are less likely to own mutual funds and more likely to either avoid equities or hold individual stocks. We are the first to empirically link individuals’ elicited probability weighting and real-world decisions under risk.
Heritability of Memory Functions and Related Brain Volumes: A Schizophrenia Spectrum Study of 214 Twins
Authors: Lemvigh Cecilie K , Brouwer Rachel M , Sahakian Barbara J , Robbins Trevor W , Johansen Louise B , Legind Christian S , Anhøj Simon J , Hilker Rikke , Hulshoff Pol Hilleke E , Ebdrup Bjørn H , Pantelis Christos , Glenthøj Birte Y , Fagerlund Birgitte
Published: November 2020

Background

Memory performance is heritable and shares partial genetic etiology with schizophrenia. How the genetic overlap between memory and schizophrenia is related to intelligence (IQ) and brain volumes has not been formally tested using twin modeling.

Methods

A total of 214 twins were recruited nationwide by utilization of the Danish registers, including monozygotic and dizygotic twin pairs concordant or discordant for a schizophrenia spectrum disorder and healthy control pairs. Memory/IQ assessments and MRI scans were performed and structural equation modeling was applied to examine the genetic and environmental effects and to quantify associations with schizophrenia liability.

Results

Significant heritability estimates were found for verbal, visual and working memory. Verbal and visual memory were associated with schizophrenia, and for visual memory the association was due to overlapping genetics. IQ was highly heritable, but only performance IQ was associated with schizophrenia. Genetic factors also contributed to total brain, right superior frontal, left rostral middle frontal and hippocampal volumes. Smaller total brain and hippocampal volumes were associated with schizophrenia, and for the left hippocampus this association was due to overlapping genetic factors. All 3 memory measures were associated with IQ, but only visual memory was associated with total brain and hippocampal volumes.

Discussion

Specific memory measures and brain volumes were moderately heritable and showed overlap with schizophrenia liability, suggesting partially shared etiological influences. Our findings further suggest that factors impacting IQ also influence memory, whereas memory impairments and brain volume abnormalities appear to represent separate pathological processes in the pathway to schizophrenia.
Acibenzolar-S-Methyl and Resistance Quantitative Trait Loci Complement Each Other to Control Apple Scab and Fire Blight
Authors: Bénéjam Juliette , Ravon Elisa , Gaucher Matthieu , Brisset Marie-Noëlle , Durel Charles-Eric , Perchepied Laure
Published: November 2020

Diversifying disease control methods is a key strategy to sustainably reduce pesticides. Plant genetic resistance has long been used to create resistant varieties. Plant resistance inducers (PRI) are also considered to promote crop health, but their effectiveness is partial and can vary according to the environment and the plant genotype. We investigated the putative interaction between intrinsic (genetic) and PRI-induced resistance in apple when affected by scab and fire blight diseases. A large F1 mapping population was challenged by each disease after a pre-treatment with acibenzolar-S-methyl (ASM) and compared with the water control. Apple scab and fire blight resistance quantitative trait loci (QTLs) were detected in both conditions and compared. ASM exhibited a strong effectiveness in reducing both diseases. When combined, QTL-controlled and ASM-induced resistance acted complementarily to reduce the symptoms from 85 to 100%, depending on the disease. In our conditions, resistance QTLs were only slightly or rarely affected by ASM treatment, despite their probable implication in various stages of the resistance buildup. Implications of these results are discussed considering already known results, the underlying mechanisms, cross protection of both types of resistance against pathogen adaptation, and practical application in orchard conditions.
Draft Genome Sequence Resource of the Citrus Stem-End Rot Fungal Pathogen Lasiodiplodia theobromae CITRA15
Authors: Zheng Qiaolin , Ozbudak Egem , Liu Guohong , Hosmani Prashant S. , Saha Surya , Flores-Gonzalez Mirella , Mueller Lukas A. , Rodrigues-Stuart Katia , Dewdney Megan M. , Lin Youjian , Zhang Jiuxu , Tarazona Yisel Carrillo , Liu Bo , Oliva Ricardo , Ritenour Mark A. , Cano Liliana M.
Published: November 2020

Lasiodiplodia theobromae is a fungal pathogen associated with perennial tropical fruit plants worldwide. In citrus, L. theobromae causes stem-end rot (Diplodia stem-end rot), a damaging postharvest disease that is aggravated when trees are also infected with the citrus greening bacteria ‘Candidatus Liberibacter asiaticus’. Due to the latent infection of L. theobromae during the preharvest stage, it becomes difficult to control the disease by chemical or physical treatment. In the current study, we sequenced and assembled strain CITRA15, the first genome of L. theobromae obtained from diseased Citrus paradise ‘Flame’ grapefruit in Florida, and thereby provided a genomic resource for future research on diagnostics, and postharvest and preharvest disease management of citrus and other fruit crops.
Prevalence of untreated surgical conditions in bateys (Sugar Workers’ Towns) of the Eastern Dominican Republic: a retrospective cross-sectional study
Authors: Eblovi Darren E. , Miller Jhomairy M. , Clitheroe Kathryn L. , Sun Se-Hwa , Daly Peter J.
Published: November 2020

Introduction:

The global burden of surgical disease is likely immense, but surgical care has been largely neglected in low- and middle-income countries, partly due to a lack of region-specific evidence describing the prevalence. In preparation for the opening of a charitable surgical center, the organization One World Surgery conducted a census, needs assessment, and a series of charitable outreach primary care clinics in several bateys (sugar workers’ towns) in the eastern Dominican Republic. This study aims to use information collected by the organization to determine the prevalence of untreated surgical conditions in an underserved region of a high-middle-income country.

Methods:

Population data from a series of bateys surrounding the city of San Pedro de Macoris on the country’s eastern plains, a region with significant sugarcane, was determined from a census and needs assessment performed by community health workers between April and December 2019. This information was used to invite patients to charitable outreach primary care clinics led by volunteer US-based physicians between September 2019 and February 2020, during which the number of patients with untreated surgical conditions was calculated.

Results:

Volunteer physicians recommended at least 1 surgery for 147 individuals among a population of 4070 (3.61%). Fifty-two percent of surgical patients were male and 36.7% were age 60 and above. The most common surgical diagnoses were cataract, pterygium, and hernias/hydroceles. The most needed specialties were ophthalmology (1.74%), general surgery (1.01%), and orthopedics (0.69%).

Conclusion:

The population of bateys (sugar workers’ towns) in the eastern Dominican Republic, a high-middle-income country, has a high prevalence of untreated surgical disease. This is likely due partly to the population of the bateys being underserved compared to the country overall, and partly to the country’s increasing life expectancy. However, since most patients with untreated surgical conditions are of working age or below, it will be important with respect to national productivity for the Dominican Republic and other high-middle-income countries to increase surgical capacity along with other more traditionally prioritized health care initiatives.
A World Without Cows
Authors: Kanter Mitch , Moore Donald
Published: November 2020

Dairy cows descended from animals that have been providing nourishment to humans for thousands of years. If cows no longer inhabited the earth, humans would lose a key source of high-quality protein and numerous other nutrients, as well as a source of revenue, livelihoods, and security for millions of people globally. Although cows are net greenhouse gas emitters, improved breeding and technology practices continue to generate more efficient cows that will continue to bring the dairy sector closer to becoming net zero emitters. In this article, intended and unintended consequences of waking up to a world without cows are explored.
Time-dependent spatial specificity of high-resolution fMRI: insights into mesoscopic neurovascular coupling
Authors: Fukuda Mitsuhiro , Poplawsky Alexander J. , Kim Seong-Gi
Published: November 2020

High-resolution functional magnetic resonance imaging (fMRI) is becoming increasingly popular because of the growing availability of ultra-high magnetic fields which are capable of improving sensitivity and spatial resolution. However, it is debatable whether increased spatial resolutions for haemodynamic-based techniques, like fMRI, can accurately detect the true location of neuronal activity. We have addressed this issue in functional columns and layers of animals with haemoglobin-based optical imaging and different fMRI contrasts, such as blood oxygenation level-dependent, cerebral blood flow and cerebral blood volume fMRI. In this review, we describe empirical evidence primarily from our own studies on how well these fMRI signals are spatially specific to the neuronally active site and discuss insights into neurovascular coupling at the mesoscale.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
More than just summed neuronal activity: how multiple cell types shape the BOLD response
Authors: Howarth Clare , Mishra Anusha , Hall Catherine N.
Published: November 2020

Functional neuroimaging techniques are widely applied to investigations of human cognition and disease. The most commonly used among these is blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. The BOLD signal occurs because neural activity induces an increase in local blood supply to support the increased metabolism that occurs during activity. This supply usually outmatches demand, resulting in an increase in oxygenated blood in an active brain region, and a corresponding decrease in deoxygenated blood, which generates the BOLD signal. Hence, the BOLD response is shaped by an integration of local oxygen use, through metabolism, and supply, in the blood. To understand what information is carried in BOLD signals, we must understand how several cell types in the brain—local excitatory neurons, inhibitory neurons, astrocytes and vascular cells (pericytes, vascular smooth muscle and endothelial cells), and their modulation by ascending projection neurons—contribute to both metabolism and haemodynamic changes. Here, we review the contributions of each cell type to the regulation of cerebral blood flow and metabolism, and discuss situations where a simplified interpretation of the BOLD response as reporting local excitatory activity may misrepresent important biological phenomena, for example with regards to arousal states, ageing and neurological disease.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Separating vascular and neuronal effects of age on fMRI BOLD signals
Authors: Tsvetanov Kamen A. , Henson Richard N. A. , Rowe James B.
Published: November 2020

Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Levels of biological plausibility
Authors: Love Bradley C.
Published: November 2020

Notions of mechanism, emergence, reduction and explanation are all tied to levels of analysis. I cover the relationship between lower and higher levels, suggest a level of mechanism approach for neuroscience in which the components of a mechanism can themselves be further decomposed and argue that scientists' goals are best realized by focusing on pragmatic concerns rather than on metaphysical claims about what is ‘real'. Inexplicably, neuroscientists are enchanted by both reduction and emergence. A fascination with reduction is misplaced given that theory is neither sufficiently developed nor formal to allow it, whereas metaphysical claims of emergence bring physicalism into question. Moreover, neuroscience's existence as a discipline is owed to higher-level concepts that prove useful in practice. Claims of biological plausibility are shown to be incoherent from a level of mechanism view and more generally are vacuous. Instead, the relevant findings to address should be specified so that model selection procedures can adjudicate between competing accounts. Model selection can help reduce theoretical confusions and direct empirical investigations. Although measures themselves, such as behaviour, blood-oxygen-level-dependent (BOLD) and single-unit recordings, are not levels of analysis, like levels, no measure is fundamental and understanding how measures relate can hasten scientific progress.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.
Rude mechanicals in brain haemodynamics: non-neural actors that influence blood flow
Authors: Das Aniruddha , Murphy Kevin , Drew Patrick J.
Published: November 2020

Fluctuations in blood oxygenation and flow are widely used to infer brain activity during resting-state functional magnetic resonance imaging (fMRI). However, there are strong systemic and vascular contributions to resting-state signals that are unrelated to ongoing neural activity. Importantly, these non-neural contributions to haemodynamic signals (or ‘rude mechanicals’) can be as large as or larger than the neurally evoked components. Here, we review the two broad classes of drivers of these signals. One is systemic and is tied to fluctuations in external drivers such as heart rate and breathing, and the robust autoregulatory mechanisms that try to maintain a constant milieu in the brain. The other class comprises local, active fluctuations that appear to be intrinsic to vascular tissue and are likely similar to active local fluctuations seen in vasculature all over the body. In this review, we describe these non-neural fluctuations and some of the tools developed to correct for them when interpreting fMRI recordings. However, we also emphasize the links between these vascular fluctuations and brain physiology and point to ways in which fMRI measurements can be used to exploit such links to gain valuable information about neurovascular health and about internal brain states.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Specific immune-regulatory transcriptional signatures reveal sex and age differences in SARS-CoV-2 infected patients
Authors: Freire Paula Paccielli , Marques Alexandre H. C. , Baiocchi Gabriela Crispim , Schimke Lena F. , Fonseca Dennyson Leandro M. , Salgado Ranieri Coelho , Filgueiras Igor Salerno , da Silva Napoleao Sarah Maria , Plaça Desirée Rodrigues , Hirata Thiago Dominguez Crespo , El Khawanky Nadia , Giil Lasse Melvaer , de Miranda Gustavo Cabral , Carvalho Robson Francisco , de Souza Ferreira Luis Carlos , Condino-Neto Antonio , Nakaya Helder Takashi Imoto , Jurisica Igor , Ochs Hans D. , Camara Niels Olsen Saraiva , Calich Vera Lúcia Garcia , Cabral-Marques Otavio
Published: November 2020

The coronavirus disease 2019 (COVID-19) fatality rate varies in different patient groups. However, the underlying mechanisms that explain this variation are poorly understood. Here, we reanalyzed and integrated public RNAseq datasets of nasopharyngeal swabs and peripheral blood leukocytes from patients with SARS-CoV-2, comparing transcription patterns according to sex, age, and viral load. We found that female and young patients infected by SARS-CoV-2 exhibited a similar transcriptomic pattern with a larger number of total (up- and downregulated) differentially expressed genes (DEGs) compared to males and elderly patients. The transcriptional analysis showed a sex-specific profile with a higher transcriptional modulation of immune response-associated genes in female and young subjects against SARS-CoV-2. The functional clustering was characterized by a highly correlated interferome network of cytokine/chemokine- and neutrophil-associated genes that were enriched both in nasopharyngeal cells and peripheral blood of COVID-19 patients. Females exhibited reduced transcriptional levels of key pro-inflammatory/neutrophil-related genes such as CXCL8 receptors (CXCR1/CXCR2), IL-1β, S100A9, ITGAM, and DBNL compared to males, which correlate with a protective gene expression profile against inflammatory damage. Our data indicate specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2. These results point out therapeutic targets to reduce morbidity and mortality of COVID-19.
Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response
Authors: Shields Adrian M , Faustini Sian E , Perez-Toledo Marisol , Jossi Sian , Allen Joel D , Al-Taei Saly , Backhouse Claire , Dunbar Lynsey , Ebanks Daniel , Emmanuel Beena , Faniyi Aduragbemi A , Garvey Mark I. , Grinbergs Annabel , McGinnell Golaleh , O’Neill Joanne , Watanabe Yasunori , Crispin Max , Wraith David. C , Cunningham Adam F , Drayson Mark T , Richter Alex G
Published: November 2020

Objective

To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19.

Design

A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19.

Setting

University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT).

Participants

956 health care workers were recruited by open invitation via UHBFT trust email and social media.

Intervention

Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables.

Results

Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity.

Conclusions and relevance

Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease. The combination of cough, and/or fever and/or anosmia identifies the majority of individuals who should self-isolate for COVID-19.
The prevalence of psychological distress and relationships with social fragmentation and isolation: a geospatial study and survey in rural Australia
Authors: Forcadela Victor , Bagheri Nasser , Slimings Claudia
Published: November 2020

Purpose

There is limited data on the effects of social isolation on rural mental health. The aim of this study was to describe the prevalence of psychological distress in a rural area of Australia while exploring the association between psychological distress and social isolation at the individual and area level.

Methods

An online cross-sectional survey of 408 adult volunteers was conducted across rural south-eastern New South Wales from October 2019 to April 2020. The Kessler 10 was used to measure psychological distress, while area-level social fragmentation was assessed using the family (ANSFIfam) and mobility (ANSFImob) components of the Australian Neighbourhood Social Fragmentation Index. The number of different occupations of people known socially was used to assess individual-level social isolation. Spatial analysis was performed to identify any spatial autocorrelation.

Results

The prevalence of high psychological distress in the sample was 29%. Using logistic regression models, there was little evidence of a relationship between high psychological distress and ANSFIfam (odds ratio (OR)=0.98, 95% confidence interval (CI)=0.93–1.03), or ANSFImob (OR=1.04, 95%CI=0.99–1.09). High psychological distress also did not appear to be associated with number of occupations known socially (OR=1.00, 95%CI=0.99–1.00). There was no significant spatial autocorrelation of psychological distress or social fragmentation at the postal area level.

Conclusion

The results suggest that social fragmentation or isolation may not have a significant effect on psychological distress in a rural setting. Nevertheless, further investigation of the effects of social isolation on mental health in rural areas is warranted.
High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease
Authors: Soria María Eugenia , Cortón Marta , Martínez-González Brenda , Lobo-Vega Rebeca , Vázquez-Sirvent Lucía , López-Rodríguez Rosario , Almoguera Berta , Mahillo Ignacio , Mínguez Pablo , Herrero Antonio , Taracido Juan Carlos , Macías-Valcayo Alicia , Esteban Jaime , Fernandez-Roblas Ricardo , Gadea Ignacio , Ruíz-Hornillos Javier , Ayuso Carmen , Perales Celia
Published: November 2020

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work is to determine a possible association between the viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we have clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or exitus. Here we report a statistically significant correlation between viral load and disease severity, being high viral load associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity, and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce the viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.
Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection
Authors: Mpande Cheleka A.M. , Rozot Virginie , Mosito Boitumelo , Musvosvi Munyaradzi , Dintwe One B , Bilek Nicole , Hatherill Mark , Scriba Thomas J. , Nemes Elisa ,   the ACS Study Team
Published: November 2020

Background

Recent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with acquisition of M.tb infection and identify a biomarker that can distinguish recent from remote infection.

Methods

Healthy South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion <6 months) and persistent (QuantiFERON-TB+ for >1.5 year) infection. We characterized M.tb-specific CD4 T cell functional (IFN-γ, TNF, IL-2, CD107, CD154), memory (CD45RA, CCR7, CD27, KLRG-1) and activation (HLA-DR) profiles by flow cytometry after CFP-10/ESAT-6 peptide pool or M.tb lysate stimulation. We then assessed the diagnostic performance of immune profiles that were differentially expressed between individuals with recent or persistent QuantiFERON-TB+.

Findings

CFP-10/ESAT-6-specific CD4 T cell activation but not functional or memory phenotypes distinguished between individuals with recent and persistent QuantiFERON-TB+. In response to M.tb lysate, recent QuantiFERON-TB+ individuals had lower proportions of highly differentiated IFN-γ+TNF+ CD4 T cells expressing a KLRG-1+ effector phenotype and higher proportions of early differentiated IFN-γ-TNF+IL-2+ and activated CD4 T cells compared to persistent QuantiFERON-TB+ individuals. Among all differentially expressed T cell features CFP-10/ESAT-6-specific CD4 T cell activation was the best performing diagnostic biomarker of recent infection.

Interpretation

Recent M.tb infection is associated with highly activated and moderately differentiated functional M.tb-specific T cell subsets, that can be used as biomarkers to distinguish between recent and remote infection.