bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability
Authors: Yu Zhenyang , Zeng Jian , Wang Jun , Cui Yaxiong , Song Xiaopeng , Zhang Yizhe , Cheng Xuan , Hou Ning , Teng Yan , Lan Yu , Chen Yeguang , Yang Xiao
Published: January 2020

Aims

Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs), a key component of the endosomal sorting complex required for transport (ESCRT), has been implicated in many essential biological processes. However, the physiological role of endogenous Hgs in the vascular system has not previously been explored. Here, we have generated brain endothelial cell (EC) specific Hgs knockout mice to uncover the function of Hgs in EC polarity and cerebrovascular stability.

Methods and results

Knockout of Hgs in brain ECs led to impaired endothelial apicobasal polarity and brain vessel collapse in mice. We determined that Hgs is essential for recycling of vascular endothelial (VE)-cadherin to the plasma membrane, since loss of Hgs blocked trafficking of endocytosed VE-cadherin from early endosomes to recycling endosomes, and impaired the motility of recycling endosomes. Supportively, overexpression of the motor kinesin family member 13A (KIF13A) restored endosomal recycling and rescued abrogated polarized trafficking and distribution of VE-cadherin in Hgs knockdown ECs.

Conclusion

These data uncover a novel physiological function of Hgs and support an essential role for the ESCRT machinery in the maintenance of EC polarity and cerebrovascular stability.
Decisions for Empire: Revisiting the 1882 Occupation of Egypt
Authors: Mulligan William
Published: January 2020

The decision of Gladstone’s government to invade and occupy Egypt in 1882 remains one of the most contentious in late nineteenth-century British political and imperial history. This article examines the decision-making process in June and July 1882, revisiting Robinson and Gallagher’s influential study in the light of more recent historiographical research and previously unused sources. It looks at who made the critical decisions, what their preoccupations were, and how they were able to get Cabinet approval. Hartington and Northbrook were the two key figures, who co-operated to overturn Gladstone’s and Granville’s policy in June 1882. Yet their co-operation was momentary and they found themselves on different sides of the argument over the participation of Indian forces and international support. Although they shared a sense of Egypt’s importance to British imperial security, they each had a distinctive approach, so that the decision to occupy cannot be reduced to a conflict between Whig pragmatists and Radical idealists. The article also shows how the Alexandria riot on 11 June altered the context of decision-making by shifting the mood in the parliamentary Liberal party towards intervention. Parliament, not the press, was the crucial site of ‘public opinion’ in the Egyptian crisis in June and July 1882.
Comparison of external apical root resorption with clear aligners and pre-adjusted edgewise appliances in non-extraction cases: a systematic review and meta-analysis
Authors: Gandhi Vaibhav , Mehta Shivam , Gauthier Marissa , Mu Jijian , Kuo Chia-Ling , Nanda Ravindra , Yadav Sumit
Published: January 2020

Objective

The aim of this study was to evaluate and compare the amount of external apical root resorption (EARR) observed during the orthodontic treatment with pre-adjusted edgewise appliance (PEA) or clear aligner therapy (CAT) and with 2D or 3D radiographic methods of measuring the root resorption.

Search strategy and selection criteria

A search of PubMed MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, LILACS, Web of Science, Dissertations & Theses Global, ClinicalTrials.gov registry, and the ISRCTN Registry was performed. Studies that have evaluated the amount of root resorption in non-extraction cases using CAT or PEA were selected for the systematic review. A meta-analysis was performed for the amount of root resorption of permanent maxillary incisors using PEA or CAT treatment modalities by either 2D or cone-beam computed tomography radiographic examination.

Data collection and analysis

Database research, elimination of duplicate studies, data extraction, and risk of bias were performed by authors independently and in duplication. A random-effect meta-analysis followed by subgroup comparisons were performed to evaluate EARR.

Results

A total of 16 studies (4 were prospective and 12 were retrospective) were identified for inclusion in the systematic review. The mean root resorption for the permanent maxillary incisors was in the range from 0.25 to 1.13 mm (overall: 0.49 mm; 95% confidence interval [CI] = 0.24 to 0.75 mm). The mean root resorption difference between CAT and PEA was statistically significant (P < 0.05) for 12 but not for 21, 11, or 22.

Limitations

One of the drawbacks is a lack of good quality prospective studies, specifically randomized clinical trials in the literature.

Conclusions and implications

Neither PEA or CAT technique leads to clinically significant root resorption (1 mm) of the maxillary incisors. The amount of EARR of maxillary incisors is not significant in comparing two treatment modalities (PEA and CAT), except for 12, where the PEA group has significantly more EARR when compared to CAT.

Registration

The protocol for this systematic review was based on the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and was registered at PROSPERO database (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018113051). This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
Translation elongation factor P (EF-P)
Authors: Hummels Katherine R , Kearns Daniel B
Published: January 2020

Translation elongation factor P (EF-P) is conserved in all three domains of life (called eIF5A and aIF5A in eukaryotes and archaea, respectively) and functions to alleviate ribosome pausing during the translation of specific sequences, including consecutive proline residues. EF-P was identified in 1975 as a factor that stimulated the peptidyltransferase reaction in vitro but its involvement in the translation of tandem proline residues was not uncovered until 2013. Throughout the four decades of EF-P research, perceptions of EF-P function have changed dramatically. In particular, while EF-P was thought to potentiate the formation of the first peptide bond in a protein, it is now broadly accepted to act throughout translation elongation. Further, EF-P was initially reported to be essential, but recent work has shown that the requirement of EF-P for growth is conditional. Finally, it is thought that post-translational modification of EF-P is strictly required for its function but recent studies suggest that EF-P modification may play a more nuanced role in EF-P activity. Here, we review the history of EF-P research, with an emphasis on its initial isolation and characterization as well as the discoveries that altered our perceptions of its function.
Yeast synthetic biology for designed cell factories producing secretory recombinant proteins
Authors: Thak Eun Jung , Yoo Su Jin , Moon Hye Yun , Kang Hyun Ah
Published: January 2020

Yeasts are prominent hosts for the production of recombinant proteins from industrial enzymes to therapeutic proteins. Particularly, the similarity of protein secretion pathways between these unicellular eukaryotic microorganisms and higher eukaryotic organisms has made them a preferential host to produce secretory recombinant proteins. However, there are several bottlenecks, in terms of quality and quantity, restricting their use as secretory recombinant protein production hosts. In this mini-review, we discuss recent developments in synthetic biology approaches to constructing yeast cell factories endowed with enhanced capacities of protein folding and secretion as well as designed targeted post-translational modification process functions. We focus on the new genetic tools for optimizing secretory protein expression, such as codon-optimized synthetic genes, combinatory synthetic signal peptides and copy number-controllable integration systems, and the advanced cellular engineering strategies, including endoplasmic reticulum and protein trafficking pathway engineering, synthetic glycosylation, and cell wall engineering, for improving the quality and yield of secretory recombinant proteins.
Accelerating numerical wave propagation using wavefield adapted meshes. Part I: forward and adjoint modelling
Authors: van Driel M , Boehm C , Krischer L , Afanasiev M
Published: January 2020

An order of magnitude speed-up in finite-element modelling of wave propagation can be achieved by adapting the mesh to the anticipated space-dependent complexity and smoothness of the waves. This can be achieved by designing the mesh not only to respect the local wavelengths, but also the propagation direction of the waves depending on the source location, hence by anisotropic adaptive mesh refinement. Discrete gradients with respect to material properties as needed in full waveform inversion can still be computed exactly, but at greatly reduced computational cost. In order to do this, we explicitly distinguish the discretization of the model space from the discretization of the wavefield and derive the necessary expressions to map the discrete gradient into the model space. While the idea is applicable to any wave propagation problem that retains predictable smoothness in the solution, we highlight the idea of this approach with instructive 2-D examples of forward as well as inverse elastic wave propagation. Furthermore, we apply the method to 3-D global seismic wave simulations and demonstrate how meshes can be constructed that take advantage of high-order mappings from the reference coordinates of the finite elements to physical coordinates. Error level and speed-ups are estimated based on convergence tests with 1-D and 3-D models.
Basic Sets for Unipotent Blocks of Finite Reductive Groups in Bad Characteristic
Authors: Chaneb Reda
Published: January 2020

We show the existence of a unitriangular basic set for unipotent blocks of simple reductive groups of classical type in bad characteristic with some exceptions. Then, we introduce an algorithm to count unipotent irreducible Brauer characters and we verify that this algorithm is effective for exceptional adjoint groups.
Trumping International Law?
Authors: Birdsall Andrea , Sanders Rebecca
Published: January 2020

From bringing back waterboarding, to violating treaty obligations, to banning Muslims, Donald J. Trump has proposed numerous extralegal policies. We examine the implications of this disdain for legality, arguing that Trump's frequent hostility and indifference to legal rules and institutions paradoxically impede his capacity to enact his promises and damage international law. To situate Trump's legal politics, we draw comparisons with the Bush and Obama administrations. As constructivists note, the vitality of legal norms is dependent not just on one state's actions, but crucially on others’ reactions. While Trump has gone beyond his predecessors in rhetorically attacking international law, the backlash he generates limits the realization of his agenda in part due to his failure to convince others to violate the law or revise legal rules in novel ways. When the administration does reluctantly pursue legal justifications for controversial policies, it is better able to overcome legal constraints and political opposition.
Downregulated long non-coding RNA LINC01093 in liver fibrosis promotes hepatocyte apoptosis via increasing ubiquitination of SIRT1
Authors: Tang Yinhe , Ma Naijing , Luo Hao , Chen Shizuan , Yu Fuxiang
Published: January 2020

The apoptosis of hepatocytes contributes to the activation of hepatic stellate cells (HSCs), thus promoting the accumulation of extracellular matrix proteins and aggravating liver fibrosis. Silent information regulator 1 (SIRT1) is an anti-fibrotic protein whose downregulation induces hepatocyte apoptosis. This study aims to identify whether SIRT1 is regulated by long non-coding RNA LINC01093 and explore its underlying mechanisms. Liver fibrosis was induced in mice using CCl4, and the differential expressions of several fibrosis-related long noncoding RNAs were detected in liver tissues. The effect of LINC01093 on cell apoptosis and viability of hepatocytes were investigated after LINC01093 overexpression or knockdown using flow cytometry and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The anti-fibrotic effect of LINC01093 overexpression was observed in vivo. LncRNA LINC01093 is downregulated in CCl4-induced liver tissues and TGF-β1-stimulated hepatocytes. Downregulated LINC01093 promoted cell apoptosis and inhibited cell viability of hepatocytes. The co-culture between LINC01093-knockdown hepatocytes and HSCs increased the expressions of pro-fibrotic proteins. Downregulated LINC01093 promoted hepatocyte apoptosis via promoting degradation and ubiquitination of SIRT1 under TGF-β1 stimulation. The injection of LINC01093-overexpressing vectors alleviated liver fibrosis in vivo. In liver fibrosis, the downregulated LINC01093 promoted hepatocyte apoptosis, which is mediated by increasing the degradation and ubiquitination of SIRT1.
Achieving Justice for Child Survivors of Conflict-related Sexual Violence in the Democratic Republic of the Congo
Authors: Perissi Daniele , Naimer Karen
Published: January 2020

In March 2015, the first major conference, or États Généraux, of the Congolese justice system was held in Kinshasa, Democratic Republic of the Congo. The conference, the mandate of which was to evaluate the functioning of the judicial system and formulate recommendations about reforms and actions to be implemented, pledged to strengthen national investigations and prosecutions of international crimes as a matter of priority. This development was significant in a country where widespread impunity for perpetrators of mass crimes, in particular conflict-related sexual violence, is rampant and exacerbates the trauma suffered by survivors. Among the cases deemed a ‘priority’, the Kavumu case was especially important. In that case, the Military Court of South Kivu found that the accused were part of an armed group, controlled by provincial lawmaker Frédéric Batumike, and together they were responsible for the rape of over 40 young girls over a three-year period. After a long and complex process, in December 2017, a mobile military court convicted 11 militia members, including the parliamentarian, of rape as a crime against humanity and sentenced them to life. In July 2018, the High Military Court confirmed the verdict. This article will provide an overview of the Kavumu case as well as the main milestones of the proceedings. The article will then discuss three features of the case that exemplify innovations and best practices — as well as pending challenges — in the prosecution of conflict-related sexual violence, including the issue of domestic immunities for international crimes; the unique, interdisciplinary protections undertaken for child victims of sexual violence in legal proceedings; and the effective collaborations among the network of medical, legal, and civil society actors supporting national efforts to combat impunity. The Kavumu case aptly illustrates how national justice institutions, working alongside international and local partners, can lead the way in achieving progress and overcoming complex challenges to advance accountability and set important precedents in the fight against impunity for conflict-related sexual violence.
Prophylactic donor lymphocyte infusion for relapse prevention: a meta-analysis
Authors: Poonsombudlert Kittika , Kewcharoen Jakrin , Prueksapraopong Chattip , Limpruttidham Nath
Published: January 2020

Objective

Primary disease relapse (PDR) of malignant hematologic conditions after standard hematopoietic stem cell transplant (HSCT) is one of the most challenging diseases; therefore ongoing researches are aiming at relapse prevention and minimizing the transplant-related side effects. Prophylactic donor lymphocytes (pDLI) had been proposed as a valuable strategy for PDR prevention, but early studies had been discouraging due to the limited benefit and possible association with acute graft-versus-host disease (aGVHD). Therefore, we conducted a meta-analysis to evaluate the association between pDLI use, PDR, aGVHD and OS.

Method

We performed a comprehensive literature search in MEDLINE, Cochrane library and Embase database from inception to May 2019 for studies that evaluated the association between pDLI and PDR. We conducted a random effect meta-analysis of 9 studies involving a total of 748 participants (pDLI = 398, non-pDLI = 350) and reported the pooled odd ratio (OR) for association of pDLI use, PDR, aGVHD and OS.

Result

We found a significant decreased odd of PDR in the pDLI group (pooled OR = 0.42, 95% CI 0.30–0.58, I2 = 0%), but there was no significant increased odd of aGVHD (pooled OR of 0.98, 95% CI 0.56–1.72, I2 = 0.8%). We also found that there was an increased odd of overall survival (OS) (pooled OR 3.17, 95% CI 1.85–5.45, I2 = 50.2%).

Conclusion

There are significantly decreased odd of PDR and increased odd of OS in the pDLI group compared to the control group, but there is no statistically significant increased odd of aGVHD as suggested by previous studies. We concluded that pDLI is a potentially valuable method for post-transplant PDR prevention.
LYMESIM 2.0: An Updated Simulation of Blacklegged Tick (Acari: Ixodidae) Population Dynamics and Enzootic Transmission of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae)
Authors: Gaff Holly , Eisen Rebecca J , Eisen Lars , Nadolny Robyn , Bjork Jenna , Monaghan Andrew J
Published: January 2020

Lyme disease is the most commonly reported vector-borne disease in the United States, and the number of cases reported each year continues to rise. The complex nature of the relationships between the pathogen (Borrelia burgdorferi sensu stricto), the tick vector (Ixodes scapularis Say), multiple vertebrate hosts, and numerous environmental factors creates challenges for understanding and predicting tick population and pathogen transmission dynamics. LYMESIM is a mechanistic model developed in the late 1990s to simulate the life-history of I. scapularis and transmission dynamics of B. burgdorferi s.s. Here we present LYMESIM 2.0, a modernized version of LYMESIM, that includes several modifications to enhance the biological realism of the model and to generate outcomes that are more readily measured under field conditions. The model is tested for three geographically distinct locations in New York, Minnesota, and Virginia. Model-simulated timing and densities of questing nymphs, infected nymphs, and abundances of nymphs feeding on hosts are consistent with field observations and reports for these locations. Sensitivity analysis highlighted the importance of temperature in host finding for the density of nymphs, the importance of transmission from small mammals to ticks on the density of infected nymphs, and temperature-related tick survival for both density of nymphs and infected nymphs. A key challenge for accurate modeling of these metrics is the need for regionally representative inputs for host populations and their fluctuations. LYMESIM 2.0 is a useful public health tool that downstream can be used to evaluate tick control interventions and can be adapted for other ticks and pathogens.
‘This ‘Merikay War’: Poetic Responses in Lancashire to the American Civil War
Authors: Rennie Simon
Published: January 2020

This article examines Lancashire commentary on the American Civil War during the Cotton Famine of 1861–65 through poetry which has recently been recovered from local newspapers. The complexity and variety of the often labouring-class subjectivities figured in the texts works to further disrupt the conventional historical view of a region united in moral and political sympathy with the Union cause, as exemplified by discourses surrounding Lincoln’s letter to the region in 1863. Much of this poetry displays an acute awareness of its place in the world. Labouring-class Lancashire people were forced by economic circumstances to confront the nature of a Victorian globalization which had proved its instability, and many began to see themselves in terms of a global subjectivity for the first time. This poetic discourse may have been materially and culturally adjacent to journalistic comment on the crisis, but poetry’s imaginative freedom and ability to compress language and hence cultural meaning often represented an amplification, distortion, or even contradiction of implied editorial comment. Nowhere was this more apparent than in the sometimes febrile context of Lancashire commentary on the American Civil War and its domestic effects. Even when no particular resolution was offered as an option the ability of Lancashire poets to represent the voice of their fellow sufferers with some degree of authenticity served to reflect the ever more intimate relationship between the Victorian global and the local which the effects of the American war demonstrated in such stark terms.
Constraining planet formation around 6–8 M⊙ stars
Authors: Veras Dimitri , Tremblay Pier-Emmanuel , Hermes J J , McDonald Catriona H , Kennedy Grant M , Meru Farzana , Gänsicke Boris T
Published: January 2020

Identifying planets around O-type and B-type stars is inherently difficult; the most massive known planet host has a mass of only about $3\, \mathrm{M}_{\odot }$. However, planetary systems which survive the transformation of their host stars into white dwarfs can be detected via photospheric trace metals, circumstellar dusty and gaseous discs, and transits of planetary debris crossing our line of sight. These signatures offer the potential to explore the efficiency of planet formation for host stars with masses up to the core-collapse boundary at $\approx 8\, \mathrm{M}_{\odot }$, a mass regime rarely investigated in planet formation theory. Here, we establish limits on where both major and minor planets must reside around $\approx 6\rm {-}8\, \mathrm{M}_{\odot }$ stars in order to survive into the white dwarf phase. For this mass range, we find that intact terrestrial or giant planets need to leave the main sequence beyond approximate minimum star–planet separations of, respectively, about 3 and 6 au. In these systems, rubble pile minor planets of radii 10, 1.0, and 0.1 km would have been shorn apart by giant branch radiative YORP spin-up if they formed and remained within, respectively, tens, hundreds, and thousands of au. These boundary values would help distinguish the nature of the progenitor of metal pollution in white dwarf atmospheres. We find that planet formation around the highest mass white dwarf progenitors may be feasible, and hence encourage both dedicated planet formation investigations for these systems and spectroscopic analyses of the highest mass white dwarfs.
Secular evolution of close-in planets: the effects of general relativity
Authors: Marzari F , Nagasawa M
Published: January 2020

Pairs of planets in a system may end up close to their host star on eccentric orbits as a consequence of planet–planet scattering, Kozai, or secular migration. In this scenario, general relativity and secular perturbations have comparable time-scales and may interfere with each other with relevant effects on the eccentricity and pericenter evolution of the two planets. We explore, both analytically and via numerical integration, how the secular evolution is changed by general relativity for a wide range of different initial conditions. We find that when the faster secular frequency approaches the general relativity precession rate, which typically occurs when the outer planet moves away from the inner one, it relaxes to it and a significant damping of the proper eccentricity of the inner planet occurs. The proper eccentricity of the outer planet is reduced as well due to the changes in the secular interaction of the bodies. The lowering of the peak eccentricities of the two planets during their secular evolution has important implications on their stability. A significant number of two-planet systems, otherwise chaotic because of the mutual secular perturbations, are found stable when general relativity is included.
Measuring stellar magnetic helicity density
Authors: Lund K , Jardine M , Lehmann L T , Mackay D H , See V , Vidotto A A , Donati J-F , Fares R , Folsom C P , Jeffers S V , Marsden S C , Morin J , Petit P
Published: January 2020

Helicity is a fundamental property of a magnetic field but to date it has only been possible to observe its evolution in one star – the Sun. In this paper, we provide a simple technique for mapping the large-scale helicity density across the surface of any star using only observable quantities: the poloidal and toroidal magnetic field components (which can be determined from Zeeman–Doppler imaging) and the stellar radius. We use a sample of 51 stars across a mass range of 0.1–1.34 M⊙ to show how the helicity density relates to stellar mass, Rossby number, magnetic energy, and age. We find that the large-scale helicity density increases with decreasing Rossby number Ro, peaking at Ro ≃ 0.1, with a saturation or decrease below that. For both fully and partially convective stars, we find that the mean absolute helicity density scales with the mean squared toroidal magnetic flux density according to the power law: $|\langle {h\, }\rangle |$ ∝ $\langle {\rm {{\it B}_{tor}}^2_{}\, \rangle }^{0.86\, \pm \, 0.04}$. The scatter in this relation is consistent with the variation across a solar cycle, which we compute using simulations and observations across solar cycles 23 and 24, respectively. We find a significant decrease in helicity density with age.
The dynamical history of the evaporating or disrupted ice giant planet around white dwarf WD J0914+1914
Authors: Veras Dimitri , Fuller Jim
Published: January 2020

Robust evidence of an ice giant planet shedding its atmosphere around the white dwarf WD J0914+1914 represents a milestone in exoplanetary science, allowing us to finally supplement our knowledge of white dwarf metal pollution, debris discs, and minor planets with the presence of a major planet. Here, we discuss the possible dynamical origins of this planet, WD J0914+1914 b. The very young cooling age of the host white dwarf (13 Myr) combined with the currently estimated planet–star separation of about 0.07 au imposes particularly intriguing and restrictive coupled constraints on its current orbit and its tidal dissipation characteristics. The planet must have been scattered from a distance of at least a few au to its current location, requiring the current or former presence of at least one more major planet in the system in the absence of a hidden binary companion. We show that WD J0914+1914 b could not have subsequently shrunk its orbit through chaotic f-mode tidal excitation (characteristic of such highly eccentric orbits) unless the planet was or is highly inflated and possibly had partially thermally self-disrupted from mode-based energy release. We also demonstrate that if the planet is currently assumed to reside on a near-circular orbit at 0.07 au, then non-chaotic equilibrium tides impose unrealistic values for the planet’s tidal quality factor. We conclude that WD J0914+1914 b either (i) actually resides interior to 0.07 au, (ii) resembles a disrupted ‘Super-Puff’ whose remains reside on a circular orbit, or (iii) resembles a larger or denser ice giant on a currently eccentric orbit. Distinguishing these three possibilities strongly motivates follow-up observations.
Faint Standards for ZYJHK from the UKIDSS and VISTA Surveys
Authors: Leggett S K , Cross Nicholas J G , Hambly Nigel C
Published: January 2020

The currently defined ‘United Kingdom Infrared Telescope (UKIRT) Faint Standards’ have JHK magnitudes between 10 and 15, with Kmedian = 11.2. These stars will be too bright for the next generation of large telescopes. We have used multi-epoch observations taken as part of the UKIRT Infrared Deep Sky Survey (UKIDSS) and the Visible and Infrared Survey Telescope for Astronomy (VISTA) surveys to identify non-variable stars with JHK magnitudes in the range 16–19. The stars were selected from the UKIDSS Deep Extragalactic Survey and Ultra Deep Survey, the WFCAM calibration data (WFCAMCAL08B), the VISTA Deep Extragalactic Observations (VIDEO), and UltraVISTA. Sources selected from the near-infrared databases were paired with the Pan-STARRS Data Release 2 of optical to near-infrared photometry and the Gaia astrometric Data Release 2. Colour indices and other measurements were used to exclude sources that did not appear to be simple single stars. From an initial selection of 169 sources, we present a final sample of 81 standard stars with ZYJHK magnitudes, or a subset, each with 20 to 600 observations in each filter. The new standards have Ksmedian = 17.5. The relative photometric uncertainty for the sample is <0.006 mag and the absolute uncertainty is estimated to be ≲ 0.02 mag. The sources are distributed equatorially and are accessible from both hemispheres.
Do we have any hope of detecting scattering between dark energy and baryons through cosmology?
Authors: Vagnozzi Sunny , Visinelli Luca , Mena Olga , Mota David F
Published: January 2020

We consider the possibility that dark energy and baryons might scatter off each other. The type of interaction we consider leads to a pure momentum exchange, and does not affect the background evolution of the expansion history. We parametrize this interaction in an effective way at the level of Boltzmann equations. We compute the effect of dark energy-baryon scattering on cosmological observables, focusing on the cosmic microwave background (CMB) temperature anisotropy power spectrum and the matter power spectrum. Surprisingly, we find that even huge dark energy-baryon cross-sections $\sigma _{xb} \sim {\cal O}({\rm b})$, which are generically excluded by non-cosmological probes such as collider searches or precision gravity tests, only leave an insignificant imprint on the observables considered. In the case of the CMB temperature power spectrum, the only imprint consists in a sub-per cent enhancement or depletion of power (depending whether or not the dark energy equation of state lies above or below −1) at very low multipoles, which is thus swamped by cosmic variance. These effects are explained in terms of differences in how gravitational potentials decay in the presence of a dark energy-baryon scattering, which ultimately lead to an increase or decrease in the late-time integrated Sachs–Wolfe power. Even smaller related effects are imprinted on the matter power spectrum. The imprints on the CMB are not expected to be degenerate with the effects due to altering the dark energy sound speed. We conclude that, while strongly appealing, the prospects for a direct detection of dark energy through cosmology do not seem feasible when considering realistic dark energy-baryon cross-sections. As a caveat, our results hold to linear order in perturbation theory.
A lack of evolution in the very bright end of the galaxy luminosity function from z ≃ 8 to 10
Authors: Bowler R A A , Jarvis M J , Dunlop J S , McLure R J , McLeod D J , Adams N J , Milvang-Jensen B , McCracken H J
Published: January 2020

We utilize deep near-infrared survey data from the UltraVISTA fourth data release (DR4) and the VIDEO survey, in combination with overlapping optical and Spitzer data, to search for bright star-forming galaxies at z ≳ 7.5. Using a full photometric redshift fitting analysis applied to the ∼6 $\, {\rm deg}^2$ of imaging searched, we find 27 Lyman break galaxies (LBGs), including 20 new sources, with best-fitting photometric redshifts in the range 7.4 < z < 9.1. From this sample, we derive the rest-frame UV luminosity function at z = 8 and z = 9 out to extremely bright UV magnitudes (MUV ≃ −23) for the first time. We find an excess in the number density of bright galaxies in comparison to the typically assumed Schechter functional form derived from fainter samples. Combined with previous studies at lower redshift, our results show that there is little evolution in the number density of very bright (MUV ∼ −23) LBGs between z ≃ 5 and z ≃ 9. The tentative detection of an LBG with best-fitting photometric redshift of z = 10.9 ± 1.0 in our data is consistent with the derived evolution. We show that a double power-law fit with a brightening characteristic magnitude (ΔM*/Δz ≃ −0.5) and a steadily steepening bright-end slope (Δβ/Δz ≃ −0.5) provides a good description of the z > 5 data over a wide range in absolute UV magnitude (−23 < MUV < −17). We postulate that the observed evolution can be explained by a lack of mass quenching at very high redshifts in combination with increasing dust obscuration within the first ${\sim}1 \, {\rm Gyr}$ of galaxy evolution.
A Behavior-Manipulating Virus Relative as a Source of Adaptive Genes forDrosophilaParasitoids
Authors: Di Giovanni Deborah , Lepetit David , Guinet Benjamin , Bennetot Bastien , Boulesteix Matthieu , Couté Yohann , Bouchez Olivier , Ravallec Marc , Varaldi Julien
Published: January 2020

Some species of parasitic wasps have domesticated viral machineries to deliver immunosuppressive factors to their hosts. Up to now, all described cases fall into the Ichneumonoidea superfamily, which only represents around 10% of hymenoptera diversity, raising the question of whether such domestication occurred outside this clade. Furthermore, the biology of the ancestral donor viruses is completely unknown. Since the 1980s, we know that Drosophila parasitoids belonging to the Leptopilina genus, which diverged from the Ichneumonoidea superfamily 225 Ma, do produce immunosuppressive virus-like structure in their reproductive apparatus. However, the viral origin of these structures has been the subject of debate. In this article, we provide genomic and experimental evidence that those structures do derive from an ancestral virus endogenization event. Interestingly, its close relatives induce a behavior manipulation in present-day wasps. Thus, we conclude that virus domestication is more prevalent than previously thought and that behavior manipulation may have been instrumental in the birth of such associations.
Characterization and Biosynthesis of Lipids in Paulinella micropora MYN1: Evidence for Efficient Integration of Chromatophores into Cellular Lipid Metabolism
Authors: Sato Naoki , Yoshitomi Toru , Mori-Moriyama Natsumi
Published: January 2020

The chromatophores found in the cells of photosynthetic Paulinella species, once believed to be endosymbiotic cyanobacteria, are photosynthetic organelles that are distinct from chloroplasts. The chromatophore genome is similar to the genomes of α-cyanobacteria and encodes about 1,000 genes. Therefore, the chromatophore is an intriguing model of organelle formation. In this study, we analyzed the lipids of Paulinella micropora MYN1 to verify that this organism is a composite of cyanobacterial descendants and a heterotrophic protist. We detected glycolipids and phospholipids, as well as a betaine lipid diacylglyceryl-3-O-carboxyhydroxymethylcholine, previously detected in many marine algae. Cholesterol was the only sterol component detected, suggesting that the host cell is similar to animal cells. The glycolipids, presumably present in the chromatophores, contained mainly C16 fatty acids, whereas other classes of lipids, presumably present in the other compartments, were abundant in C20 and C22 polyunsaturated fatty acids. This suggests that chromatophores are metabolically distinct from the rest of the cell. Metabolic studies using isotopically labeled substrates showed that different fatty acids are synthesized in the chromatophore and the cytosol, which is consistent with the presence of both type I and type II fatty acid synthases, supposedly present in the cytosol and the chromatophore, respectively. Nevertheless, rapid labeling of the fatty acids in triacylglycerol and phosphatidylcholine by photosynthetically fixed carbon suggested that the chromatophores efficiently provide metabolites to the host. The metabolic and ultrastructural evidence suggests that chromatophores are tightly integrated into the whole cellular metabolism.
Statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis: a propensity-score matched longitudinal cohort study
Authors: Sarmanova Aliya , Doherty Michael , Kuo Changfu , Wei Jie , Abhishek Abhishek , Mallen Christian , Zeng Chao , Wang Yilun , Lei Guanghua , Zhang Weiya
Published: January 2020

Objective

Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA.

Methods

This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21–28%), medium (32–38%) or high (42–55%) intensity.

Results

A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75–0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63–0.94) but not OA (0.97, 0.94–1.01).

Conclusion

Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted.
Clinical trial data transparency and GDPR compliance: Implications for data sharing and open innovation
Authors: Minssen Timo , Rajam Neethu , Bogers Marcel
Published: January 2020

Recent European Union (EU) initiatives and legislation have considerably increased public access to clinical trials data (CTD). These developments are generally much welcomed for the enhancement of science, trust, and open innovation. However, they also raise many questions and concerns, not least at the interface between CTD transparency and other areas of evolving EU law on the protection of trade secrets, IPRs, and privacy. This article focuses on privacy issues and on the interrelation between developments in transparency and the EU’s new General Data Protection Regulation 2016/679 (GDPR). More specifically, this article examines: (1) the origins and rationales of EU transparency regulations, including the incidents and concerns that have shaped them; (2) the features and implications of the GDPR which are relevant in the context of clinical trials; and (3) the risk for tensions between the GDPR and the policy goals of CTD transparency, as well as implications for data sharing and open innovation. Ultimately, we elaborate on factors that should be carefully considered and addressed to reap the full benefits of CTD transparency.
Evolution of the Resistance of Botrytis cinerea to Carbendazim and the Current Efficacy of Carbendazim Against Gray Mold After Long-Term Discontinuation
Authors: He Leiming , Cui Kaidi , Li Tongtong , Song Yufei , Liu Ning , Mu Wei , Liu Feng
Published: January 2020

Gray mold caused by Botrytis cinerea is a fungal disease that critically threatens agricultural production, and carbendazim was the first fungicide used to control B. cinerea. However, B. cinerea developed serious resistance to carbendazim, and this fungicide has thus rarely been used in the past decade in China. Due to the extended discontinuation of carbendazim use, the evolution of the resistance of B. cinerea to carbendazim in recent years is unclear, and whether carbendazim can effectively control gray mold is largely unknown. Therefore, this study determined the sensitivity of 407 B. cinerea isolates collected from 2014 to 2018 to carbendazim and the ability of carbendazim to control gray mold in the field. The results showed that the frequency of B. cinerea isolates resistant to carbendazim remained above 95%. Three different mutation types responsible for the resistance of B. cinerea to carbendazim were identified at codon 198 in the β-tubulin gene sequence: E198V (changed from GAG to GTG), E198A (changed from GAG to GCG), and E198K (changed from GAG to AAG). Over the last 5 years, E198V was the major mutation. However, an analysis of its evolution revealed that the percentage of the E198V mutation declined after 2017 to 56.5% in 2018. In addition, the proportion of isolates with the E198K mutation decreased over time, and no isolates with this mutation were found in either 2017 or 2018. The proportion of the E198A mutation increased over the 5-year test period to reach 43.5% in 2018. Furthermore, three greenhouse experiments demonstrated that carbendazim has lost its ability to control gray mold. We attribute the above findings to our results showing that the carbendazim-resistant isolates had no fitness penalties compared with the carbendazim-sensitive isolates for sporulation and mycelial growth. In particular, the E198A mutant isolates exhibited a strong ability to sporulate, suggesting that the E198A mutation might become dominant in the future. Interestingly, the results showed that carbendazim-sensitive isolates could be easily controlled by four conventional fungicides, namely boscalid, procymidone, iprodione, and pyrimethanil, with mean EC50 values of 0.71 ± 0.2 mg liter−1, 1.33 ± 0.39 mg liter−1, 0.59 ± 0.33 mg liter−1, and 6.02 ± 3.02 mg liter−1, respectively. In conclusion, carbendazim has lost its application value and is ineffective for the control of gray mold.
Apixaban-induced leukocytoclastic vasculitis
Authors: Esbech Peter , Schmidt Jakob Nøhr , Andersen Lone Kærslund , Damkier Per
Published: January 2020

Introduction:

Drug-induced vasculitis is a rare adverse drug reaction and the potential to induce such a reaction is often established postmarketing. Leukocytoclastic vasculitis - a subtype of drug-induced vasculitis - often presents itself with palpable purpuric lesions, and often within weeks of initial administration.

Case-description:

We present a 62-year-old male who presented with leukocytoclastic vasculitis within the first 8 days of apixaban-initiation. Symptoms improved upon discontinuation and resolved after several months of prednisone therapy.

Literature review:

We conducted a search on PubMed, which yielded 10 reports of leukocytoclastic vasculitis induced by NOACs, of these 10 only 1 had been caused by apixaban, 4 caused by dabigatran and 5 had been caused by rivaroxaban. Of these cases, one presented with leukocytoclastic vasculitis induced by both rivaroxaban and dabigatran, and one case presented successful switch from apixaban to rivaroxaban.

Conclusion:

Apixaban-induced leukocytoclastic vasculitis is a rare but serious and important adverse reaction.
Factors governing orthologous RpoD and H-NS evolution in Salmonella enterica Serovar Typhimurium and Escherichia coli
Authors: Mogre Aalap , Dorman Charles
Published: January 2020

Pathogenicity island acquisition is considered to be a costly process that in turn allows bacteria to explore new niches. While pathogenicity islands are known to be well integrated into existing regulatory networks in Salmonella, we do not understand whether these islands have influenced the evolution of transcription factor coding sequence itself. Here, we exchanged two antagonisticly-acting bacterial transcription factors, RpoD (σ70) and H-NS, singly or combinatorially, between the related Gram-negative bacteria Salmonella enterica Serovar Typhimurium SL1344 and Escherichia coli str. K12 substr. MG1655, to understand their functional divergence in relation to pathogenicity island expression in Salmonella. Exchanging rpoD resulted in a small growth defect in Salmonella, while exchanging hns did not. We saw a strong upregulation of pathogenicity island expression in response to rpoD exchange, while only a very weak upregulation in response to HNS exchange. Exchanging both rpoD and hns in Salmonella resulted in a further upregulation of these islands. Using two different versions of the SPI1 regulatory knockout, ΔhilA and ΔhilD, where ΔhilA knocks out only SPI1 expression and ΔhilD knocks out both SPI1 and SPI2 expression, we show that both SPI1 and SPI2 expression are costly, and that their up-regulation is the cause of the growth defect in response to rpoD exchange. Thus, we show that both RpoD and H-NS sequence evolution in Salmonella were geared towards constraining pathogenicity island expression, the expression cost of these islands very clearly being a driver of RpoD evolution.
The role of mature mycolic acids in mycobacterial biofilm formation and interactions with the human complement system
Authors: Halkerston Rachel , Davies Katherine , Tolley Howard , Keating Thomas , Taylor Stephen , Alderwick Luke , Bacon Joanna
Published: January 2020

Tuberculosis, causative agent Mycobacterium tuberculosis, caused an estimated 10 million new cases and 1.6 million deaths in 2017.

Mycobacterial cell wall components are important for host-pathogen interactions and modulating the innate and adaptive immune response. Much is understood about the interplay between bacterial phenotype, cell wall modulation and interaction with aspects of the immune response. However, the impact of phenotype, such as biofilms on complement system activation, has not been studied in-depth.

M. tuberculosis may persist as biofilms in a chronic, non-replicating state. Mycolic acids are a major cell wall lipid and their accumulation is a hallmark of biofilm formation. M. smegmatis was mutated in gene MSMEG4722(orthologof M. tuberculosis Rv2509) (ΔMSMEG4722)which encodes a reductase involved in the final step of mycolic acid biosynthesis.

Using ΔMSMEG4722,this project explored the role of mycolic acid maturation in biofilm development, determined the relationship between lipids and complement activity with planktonic or biofilm bacteria.

Thin-layer chromatography of ΔMSMEG4722 biofilms displayed a loss of mature free mycolic acid compared to M. smegmatis, but accumulated un-reduced free mycolate. In both biofilm and planktonicΔMSMEG4722, distribution of the virulence factor trehalose dimycolate changed throughout the cell wall compared to M. smegmatis.

Flow cytometry analysis of the deposition of complement opsonin C3b revealed increased C3 on planktonic ΔMSMEG4722 compared to M. smegmatis, but this difference was not observed on bacteria from biofilms.

Evidence from this work suggests mycolic acid maturation is important for biofilm development and plays a role in complement activation on mycobacteria.