bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropathology of microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
Authors: Magaki Shino , Chen Zesheng , Severance Alyscia , Williams Christopher K , Diaz Ramiro , Fang Chuo , Khanlou Negar , Yong William H , Paganini-Hill Annlia , Kalaria Rajesh N , Vinters Harry V , Fisher Mark
Published: January 2023

Cerebral microbleeds (CMBs) detected on magnetic resonance imaging are common in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The neuropathologic correlates of CMBs are unclear. In this study, we characterized findings relevant to CMBs in autopsy brain tissue of 8 patients with genetically confirmed CADASIL and 10 controls within the age range of the CADASIL patients by assessing the distribution and extent of hemosiderin/iron deposits including perivascular hemosiderin leakage (PVH), capillary hemosiderin deposits, and parenchymal iron deposits (PID) in the frontal cortex and white matter, basal ganglia and cerebellum. We also characterized infarcts, vessel wall thickening, and severity of vascular smooth muscle cell degeneration. CADASIL subjects had a significant increase in hemosiderin/iron deposits compared with controls. This increase was principally seen with PID. Hemosiderin/iron deposits were seen in the majority of CADASIL subjects in all brain areas. PVH was most pronounced in the frontal white matter and basal ganglia around small to medium sized arterioles, with no predilection for the vicinity of vessels with severe vascular changes or infarcts. CADASIL subjects have increased brain hemosiderin/iron deposits but these do not occur in a periarteriolar distribution. Pathogenesis of these lesions remains uncertain.
Cell wall fucosylation in Arabidopsis influences control of leaf water loss and alters stomatal development and mechanical properties
Authors: Panter Paige E , Seifert Jacob , Dale Maeve , Pridgeon Ashley J , Hulme Rachel , Ramsay Nathan , Contera Sonia , Knight Heather
Published: January 2023

The Arabidopsis sensitive-to-freezing8 (sfr8) mutant exhibits reduced cell wall (CW) fucose levels and compromised freezing tolerance. To examine whether CW fucosylation also affects the response to desiccation, we tested the effect of leaf excision in sfr8 and the allelic mutant mur1-1. Leaf water loss was strikingly higher than in the wild type in these, but not other, fucosylation mutants. We hypothesized that reduced fucosylation in guard cell (GC) walls might limit stomatal closure through altering mechanical properties. Multifrequency atomic force microscopy (AFM) measurements revealed a reduced elastic modulus (Eʹ), representing reduced stiffness, in sfr8 GC walls. Interestingly, however, we discovered a compensatory mechanism whereby a concomitant reduction in the storage modulus (Eʹʹ) maintained a wild-type viscoelastic time response (tau) in sfr8. Stomata in intact leaf discs of sfr8 responded normally to a closure stimulus, abscisic acid, suggesting that the time response may relate more to closure properties than stiffness does. sfr8 stomatal pore complexes were larger than those of the wild type, and GCs lacked a fully developed cuticular ledge, both potential contributors to the greater leaf water loss in sfr8. We present data that indicate that fucosylation-dependent dimerization of the CW pectic domain rhamnogalacturonan-II may be essential for normal cuticular ledge development and leaf water retention.
Glutathione-mediated thermomorphogenesis and heat stress responses in Arabidopsis thaliana
Authors: Dard Avilien , Weiss Alizée , Bariat Laetitia , Auverlot Juline , Fontaine Valentine , Picault Nathalie , Pontvianne Frédéric , Riondet Christophe , Reichheld Jean-Philippe
Published: January 2023

In the context of climate change, the global rise of temperature and intense heat waves affect plant development and productivity. Among the molecular perturbations that high temperature induces in living cells is the accumulation of reactive oxygen species (ROS), which perturbs the cellular redox state. In plants, the dynamics of the cellular and subcellular redox state have been poorly investigated under high temperature. Glutathione plays a major role in maintaining the cellular redox state. We investigated its contribution in adaptation of Arabidopsis thaliana to contrasting high temperature regimes: high ambient temperature inducing thermomorphogenesis and heat stress affecting plant viability. Using the genetically encoded redox marker roGFP2, we show that high temperature regimes lead to cytoplasmic and nuclear oxidation and impact the glutathione pool. This pool is restored within a few hours, which probably contributes to plant adaptation to high temperatures. Moreover, low glutathione mutants fail to adapt to heat stress and to induce thermomorphogenesis, suggesting that glutathione is involved in both heat adaptation mechanisms. We also evaluate the transcriptomic signature in the two high temperature regimes and identified gene expression deviations in low glutathione mutants, which might contribute to their sensitivity to high temperature. Thus, we define glutathione as a major player in the adaptation of Arabidopsis to contrasting high temperature regimes.
Fluoride and gallein inhibit polyphosphate accumulation by oral pathogen Rothia dentocariosa
Authors: Kumar Dhiraj , Mandal Subhrangshu , Bailey Jake V , Flood Beverly E , Jones Robert S
Published: January 2023

The uptake and storage of extracellular orthophosphate (Pi) by polyphosphate (polyP) accumulating bacteria may contribute to mineral dissolution in the oral cavity. To test the effect of potential inhibitors of polyP kinases on Rothia dentocariosa, gallein (0, 25, 50, and 100 μM) and fluoride (0, 50, and 100 ppm) were added to R. dentocariosa cultures grown in brain-heart infusion broth. At a late log growth phase (8 h), extracellular Pi was measured using an ascorbic acid assay, and polyP was isolated from bacterial cells treated with RNA/DNAases using a neutral phenol/chloroform extraction. Extracts were hydrolyzed and quantified as above. Gallein and fluoride had minor effects on bacterial growth with NaF having a direct effect on media pH. Gallein (≥25 μM) and fluoride (≥50 ppm) attenuated the bacterial drawdown of extracellular Pi by 56.7% (P < 0.05) and 37.3% (P < 0.01). There was a corresponding polyP synthesis decrease of 73.2% (P < 0.0001) from gallein and 83.1% (P < 0.0001) from fluoride. Attenuated total reflectance-Fourier-transform infrared spectroscopy validated the presence of polyP and its reduced concentration in R. dentocariosa bacterial cells following gallein and fluoride treatment. Rothia dentocariosa can directly change extracellular Pi and accumulate intracellular polyP, but the mechanism is attenuated by gallein and NaF.
A unified logical framework for explanations in classifier systems
Authors: Liu Xinghan , Lorini Emiliano
Published: January 2023

Recent years have witnessed a renewed interest in the explanation of classifier systems in the field of explainable AI (XAI). The standard approach is based on propositional logic. We present a modal language which supports reasoning about binary input classifiers and their properties. We study a family of classifier models, axiomatize it as two proof systems regarding the cardinality of the language and show completeness of our axiomatics. Moreover, we show that the satisfiability checking problem for our modal language is NEXPTIME-complete in the infinite-variable case, while it becomes polynomial in the finite-variable case. We moreover identify an interesting NP fragment of our language in the infinite-variable case. We leverage the language to formalize counterfactual conditional as well as a variety of notions of explanation including abductive, contrastive and counterfactual explanations and biases. Finally, we present two extensions of our language: a dynamic extension by the notion of assignment enabling classifier change and an epistemic extension in which the classifier’s uncertainty about the actual input can be represented.
A unified catalogue-level reanalysis of stage-III cosmic shear surveys
Authors: Longley Emily P , Chang Chihway , Walter Christopher W , Zuntz Joe , Ishak Mustapha , Mandelbaum Rachel , Miyatake Hironao , Nicola Andrina , Pedersen Eske M , Pereira Maria E S , Prat Judit , Sánchez J , Secco Lucas F , Tröster Tilman , Troxel Michael , Wright Angus H ,   The LSST Dark Energy Science Collaboration
Published: January 2023

Cosmological parameter constraints from recent galaxy imaging surveys are reaching percent-level accuracy on the effective amplitude of the lensing signal, S8. The upcoming Legacy Survey of Space and Time (LSST) of the Vera C. Rubin Observatory will produce subpercent level measurements of cosmological parameters, providing a milestone test of the ΛCDM model. To supply guidance to the upcoming LSST analysis, it is important to understand thoroughly the results from different recent galaxy imaging surveys and assess their consistencies. In this work, we perform a unified catalogue-level reanalysis of three cosmic shear data sets: the first year data from the Dark Energy Survey (DES-Y1), the 1000 deg2 data set from the Kilo-Degree Survey (KiDS-1000), and the first year data from the Hyper Suprime-Cam Subaru Strategic Program (HSC-Y1). We utilize a pipeline developed and rigorously tested by the LSST Dark Energy Science Collaboration to perform the reanalysis and assess the robustness of the results to analysis choices. We find the S8 constraint to be robust to two different small-scale modelling approaches, and varying choices of cosmological priors. Our unified analysis allows the consistency of the surveys to be rigorously tested, and we find the three surveys to be statistically consistent. Due to the partially overlapping footprint, we model the cross-covariance between KiDS-1000 and HSC-Y1 approximately when combining all three data sets, resulting in a 1.6–1.9 per cent constraint on S8 given different assumptions on the cross-covariance.
Anomalous compressible mode generation by global frame projections of pure Alfven mode
Authors: Yuen Ka Ho , Yan Huirong , Lazarian Alex
Published: January 2023

Alfven wave is the single most important physical phenomenon of magneto-hydrodynamic (MHD) turbulence and has far-reaching impact to almost all studies related to astrophysical magnetic field. Yet the restoration of the Alfven wave fluctuations from a given magnetic field, aka the local Alfven wave problem, is never properly addressed in literature albeit its importance. Previous works model the Alfven wave fluctuation as the perturbation along a straight-line, constant magnetic field. However, Lazarian & Pogosyan (2012) suggested that the decomposition of Alfven wave along a straight line, aka. the global frame decomposition, has a factor of discrepancy to the true local Alfven wave fluctuation. Here, we provide a geometric interpretation on how the local Alfven wave is related to the global frame through the use of vector frame formulation. We prove both analytically and numerically that the local frame Alfven wave is an orthogonal transformation of that of the global frame and related by the local Alfvenic Mach number. In other words, when we observe Alfven wave in the global frame of reference, some of the Alfven wave will be mistaken as compressible waves. The importance of frame choices has a far-reaching impact to the analytical studies of MHD turbulence. Combining the frame formalism and the new techniques we can have accurate measurement to some of the fundamental turbulence properties like the inclination angle of mean magnetic field relative to the line of sight.
The SCUBA-2 Large eXtragalactic Survey: 850μm map, catalogue and the bright-end number counts of theXMM-LSS field
Authors: Garratt T K , Geach J E , Tamura Y , Coppin K E K , Franco M , Ao Y , Chen C -C , Cheng C , Clements D L , Dai Y S , Dannerbauer H , Greve T R , Hatsukade B , Hwang H S , Jiang L , Kohno K , Koprowski M P , Michałowski M J , Sawicki M , Scott D , Shim H , Takeuchi T T , Wang W -H , Xue Y Q , Yang C
Published: January 2023

We present $850\, \mu {\rm m}$ imaging of the XMM-LSS field observed for 170 h as part of the James Clerk Maxwell Telescope SCUBA-2 Large eXtragalactic Survey (S2LXS). S2LXS XMM-LSS maps an area of $9\, {\rm deg}^2$, reaching a moderate depth of $1\sigma \simeq 4\, {\rm mJy\, beam^{-1}}$. This is the largest contiguous area of extragalactic sky mapped by James Clerk Maxwell Telescope (JCMT) at $850\, \mu {\rm m}$ to date. The wide area of the S2LXS XMM-LSS survey allows us to probe the ultra-bright ($S_{\rm 850\mu m}\gtrsim 15\, {\rm mJy}$), yet rare submillimetre population. We present the S2LXS XMM-LSS catalogue, which comprises 40 sources detected at >5σ significance, with deboosted flux densities in the range of $7$–$48\, {\rm mJy}$. We robustly measure the bright-end of the $850\, \mu {\rm m}$ number counts at flux densities ${\gt }7\, {\rm mJy}$, reducing the Poisson errors compared to existing measurements. The S2LXS XMM-LSS observed number counts show the characteristic upturn at bright fluxes, expected to be motivated by local sources of submillimetre emission and high-redshift strongly lensed galaxies. We find that the observed $850\, \mu {\rm m}$ number counts are best reproduced by model predictions that include either strong lensing or source blending from a 15-arcsec beam, indicating that both may make an important contribution to the observed overabundance of bright single dish $850\, \mu {\rm m}$ selected sources. We make the S2LXS XMM-LSS $850\, \mu {\rm m}$ map and >5σ catalogue presented here publicly available.
Merging black holes in dwarf galaxies: calculating binary black hole coalescence time-scales from simulations for LISA detection
Authors: De Cun Victoria I , Bellovary Jillian M , Katz Michael L
Published: January 2023

Supermassive black holes (SMBHs) merging in dwarf galaxies will be detectable by the Laser Interferometer Space Antenna (LISA) in the mid-2030s. Previous cosmological hydrodynamic simulations have shown the prediction of massive BHs merging in dwarf galaxies, but these simulations are limited by their resolution and cannot follow BH pairs all the way to coalescence. We calculate the delay time between BH pairing and merger based on the properties of the BHs and their host galaxies, and use these properties to calculate gravitational wave strains for eleven different binary BHs that merge inside dwarf galaxies from eight cosmological simulations. This delay time calculation accounts for dynamical friction due to gas and stars, loss-cone scattering, and hardening of the binary due to gravitational radiation. Out of the eleven BH mergers in the simulations, five BH pairs will merge within 0.8–8 Gyr of forming a close pair and could be observed by LISA, and the remaining six are unresolved due to resolution limitations of the simulation. As all five of the resolved close pairs merge within a Hubble time, we make the broad estimate that close SMBH pairs in dwarf galaxies will merge and be detectable by LISA, but this estimate depends on either the presence of gas during orbital decay or a solution to the dynamical buoyancy problem in cored potentials.
Restoring cosmological concordance with early dark energy and massive neutrinos?
Authors: Reeves Alexander , Herold Laura , Vagnozzi Sunny , Sherwin Blake D , Ferreira Elisa G M
Published: January 2023

The early dark energy (EDE) solution to the Hubble tension comes at the cost of an increased clustering amplitude that has been argued to worsen the fit to galaxy clustering data. We explore whether freeing the total neutrino mass Mν, which can suppress small-scale structure growth, improves EDE’s fit to galaxy clustering. Using Planck Cosmic Microwave Background and BOSS galaxy clustering data, a Bayesian analysis shows that freeing Mν does not appreciably increase the inferred EDE fraction fEDE: we find the 95 per cent C.L. upper limits fEDE < 0.092 and $M_{\nu }\lt 0.15\, {\rm eV}$. Similarly, in a frequentist profile likelihood setting (where our results support previous findings that prior volume effects are important), we find that the baseline EDE model (with $M_{\nu }=0.06\, {\rm eV}$) provides the overall best fit. For instance, compared to baseline EDE, a model with $M_\nu =0.24\, {\rm eV}$ maintains the same H0(km/s/Mpc) = (70.08, 70.11, respectively) whilst decreasing S8 = (0.837, 0.826) to the ΛCDM level, but worsening the fit significantly by Δχ2 = 7.5. For the datasets used, these results are driven not by the clustering amplitude, but by background modifications to the late-time expansion rate due to massive neutrinos, which worsen the fit to measurements of the BAO scale.
Rp attractors static neutron star phenomenology
Authors: Oikonomou Vasilis K
Published: January 2023

In this work, we study the neutron star phenomenology of Rp attractor theories in the Einstein frame. The Einstein frame Rp attractor theories have the attractor property that they originate from a large class of Jordan frame scalar theories with arbitrary non-minimal coupling. These theories in the Einstein frame provide a viable class of inflationary models, and in this work we investigate their implications on static neutron stars. We numerically solve the Tolman–Oppenheimer–Volkoff equations in the Einstein frame, for three distinct equations of state, and we provide the mass–radius diagrams for several cases of interest of the Rp attractor theories. We confront the results with several timely constraints on the radii of specific mass neutron stars, and as we show, only a few cases corresponding to specific equations of state pass the stringent tests on neutron stars phenomenology.
NEOROCKS project: surface properties of small near-Earth asteroids
Authors: Hromakina T , Birlan M , Barucci M A , Fulchignoni M , Colas F , Fornasier S , Merlin F , Sonka A , Anghel S , Poggiali G , Belskaya I , Perna D , Dotto E ,   the NEOROCKS team, Dotto E , Banaszkiewicz M , Banchi S , Barucci M A , Bernardi F , Birlan M , Carry B , Cellino A , De Leon J , Lazzarin M , Mazzotta Epifani E , Mediavilla A , Nomen Torres J , Perna D , Perozzi E , Pravec P , Snodgrass C , Teodorescu C , Anghel S , Bertolucci A , Calderini F , Colas F , Del Vigna A , Dell'Oro A , Di Cecco A , Dimare L , Fatka P , Fornasier S , Frattin E , Frosini P , Fulchignoni M , Gabryszewski R , Giardino M , Giunta A , Hromakina T , Huntingford J , Ieva S , Kotlarz J P , La Forgia F , Licandro J , Medeiros H , Merlin F , Pinna F , Polenta G , Popescu M , Rozek A , Scheirich P , Sergeyev A , Sonka A , Valsecchi G B , Wajer P , Zinzi A
Published: January 2023

We present new results of the observing program which is a part of the NEOROCKS project aimed to improve knowledge on physical properties of near-Earth Objects (NEOs) for planetary defense. Photometric observations were performed using the 1.2-m telescope at the Haute-Provence observatory (France) in the BVRI filters of the Johnson–Cousins photometric systems between June 2021 and April 2022. We obtained new surface colours for 42 NEOs. Based on the measured colours, we classified 20 objects as S-complex, nine as C-complex, nine as X-complex, two as D-type, one object as V-type, and one object remained unclassified. For all the observed objects, we estimated their absolute magnitudes and diameters. Combining these new observations with the previously acquired data within the NEOROCKS project extended our data set to 93 objects. The majority of objects in the data set with diameters D < 500 m belongs to a group of silicate bodies, which could be related to observational bias. Based on MOID and ΔV values we selected 14 objects that could be accessible by a spacecraft. Notably, we find D-type asteroid (163014) 2001 UA5 and A-type asteroid 2017 SE19 to be of particular interest as possible space mission targets.
Isolated and dynamical black hole mergers withB-POP: the role of star formation and dynamics, star cluster evolution, natal kicks, mass and spins, and hierarchical mergers
Authors: Arca Sedda Manuel , Mapelli Michela , Benacquista Matthew , Spera Mario
Published: January 2023

The current interpretation of LIGO–Virgo–KAGRA data suggests that the primary mass function of merging binary black holes (BBHs) at redshift z ≲ 1 contains multiple structures, while spins are relatively low. Theoretical models of BBH formation in different environments can provide a key to interpreting the population of observed mergers, but they require the simultaneous treatment of stellar evolution and dynamics, galaxy evolution, and general relativity. We present B-POP, a population synthesis tool to model BBH mergers formed in the field or via dynamical interactions in young, globular, and nuclear clusters. Using B-POP, we explore how black hole (BH) formation channels, star cluster evolution, hierarchical mergers, and natal BH properties affect the population of BBH mergers. We find that the primary mass distribution of BBH mergers extends beyond $M_1 \simeq 200\, {}$ M⊙, and the effective spin parameter distribution hints at different natal spins for single and binary BHs. Observed BBHs can be interpreted as members of a mixed population comprised of $\sim 34{{\ \rm per\ cent}} \, {}(66{{\ \rm per\ cent}})$ isolated (dynamical) BBHs, with the latter likely dominating at redshift z > 1. Hierarchical mergers constitute the $4.6\!-\!7.9{{\ \rm per\ cent}}$ of all mergers in the reference model, dominating the primary mass distribution beyond $M_1 \gt 65\, {}$ M⊙. The inclusion of cluster mass-loss and expansion causes an abrupt decrease in the probability for mergers beyond the third generation to occur. Considering observational biases, we find that $2.7\!-\!7.5{{\ \rm per\ cent}}$ of mock mergers involve intermediate-mass black hole (IMBH) seeds formed via stellar collisions. Comparing this percentage to observed values will possibly help us to constrain IMBH formation mechanisms.
SN 2018hna: Adding a piece to the puzzles of the explosion of blue supergiants
Authors: Xiang Danfeng , Wang Xiaofeng , Zhang Xinghan , Sai Hanna , Zhang Jujia , Brink Thomas G , Filippenko Alexei V , Mo Jun , Zhang Tianmeng , Chen Zhihao , Dessart Luc , Li Zhitong , Yan Shengyu , Blinnikov Sergei I , Rui Liming , Baron E , DerKacy J M
Published: January 2023

We present extensive optical/ultraviolet observations and modelling analysis for the nearby SN 1987A-like peculiar Type II supernova (SN) 2018hna. Both photometry and spectroscopy covered phases extending to >500 d after the explosion, making it one of the best-observed SN II of this subtype. SN 2018hna is obviously bluer than SN 1987A during the photospheric phase, suggesting higher photospheric temperature, which may account for weaker Ba ii λ6142 lines in its spectra. Analysis of early-time temperature evolution suggests a radius of ∼45 R⊙ for the progenitor of SN 2018hna, consistent with a blue supergiant (BSG). By fitting the bolometric light curve with hydrodynamical models, we find that SN 2018hna has an ejecta mass of ∼(13.7–17.7) M⊙, a kinetic energy of ∼(1.0–1.2) × 1051 erg, and a 56Ni mass of about 0.05 M⊙. Moreover, based on standard stellar evolution and the oxygen mass (0.44–0.73 M⊙) deduced from nebular [O i] lines, the progenitor of SN 2018hna is expected to have an initial main-sequence mass <16 M⊙. In principle, such a relatively low-mass star cannot end as a BSG just before core-collapse, except some unique mechanisms are involved, such as rapid rotation, restricted semiconvection, etc. On the other hand, binary scenario may be more favourable, like in the case of SN 1987A. While the much lower oxygen mass inferred for SN 2018hna may imply that its progenitor system also had much lower initial masses than that of SN 1987A.
Inhibited complete folding of consecutive human telomeric G-quadruplexes
Authors: Kristoffersen Emil Laust , Coletta Andrea , Lund Line Mørkholt , Schiøtt Birgit , Birkedal Victoria
Published: January 2023

Noncanonical DNA structures, termed G-quadruplexes, are present in human genomic DNA and are important elements in many DNA metabolic processes. Multiple sites in the human genome have G-rich DNA stretches able to support formation of several consecutive G-quadruplexes. One of those sites is the telomeric overhang region that has multiple repeats of TTAGGG and is tightly associated with both cancer and aging. We investigated the folding of consecutive G-quadruplexes in both potassium- and sodium-containing solutions using single-molecule FRET spectroscopy, circular dichroism, thermal melting and molecular dynamics simulations. Our observations show coexistence of partially and fully folded DNA, the latter consisting of consecutive G-quadruplexes. Following the folding process over hours in sodium-containing buffers revealed fast G-quadruplex folding but slow establishment of thermodynamic equilibrium. We find that full consecutive G-quadruplex formation is inhibited by the many DNA structures randomly nucleating on the DNA, some of which are off-path conformations that need to unfold to allow full folding. Our study allows describing consecutive G-quadruplex formation in both nonequilibrium and equilibrium conditions by a unified picture, where, due to the many possible DNA conformations, full folding with consecutive G-quadruplexes as beads on a string is not necessarily achieved.
The enterohemorrhagicEscherichia coliinsertion sequence-excision enhancer protein is a DNA polymerase with microhomology-mediated end-joining activity
Authors: Calvo Patricia A , Mateo-Cáceres Víctor , Díaz-Arco Silvia , Redrejo-Rodríguez Modesto , de Vega Miguel
Published: January 2023

Bacterial genomes contain an abundance of transposable insertion sequence (IS) elements that are essential for genome evolution and fitness. Among them, IS629 is present in most strains of enterohemorrhagic Escherichia coli O157 and accounts for many polymorphisms associated with gene inactivation and/or genomic deletions. The excision of IS629 from the genome is promoted by IS-excision enhancer (IEE) protein. Despite IEE has been identified in the most pathogenic serotypes of E. coli, its biochemical features that could explain its role in IS excision are not yet understood. We show that IEE is present in >30% of all available E. coli genome assemblies, and is highly conserved and very abundant within enterohemorrhagic, enteropathogenic and enterotoxigenic genomes. In vitro analysis of the recombinant protein from E. coli O157:H7 revealed the presence of a Mn2+-dependent error-prone DNA polymerase activity in its N-terminal archaeo-eukaryotic primase (AEP) domain able to promote dislocations of the primer and template strands. Importantly, IEE could efficiently perform in vitro an end-joining reaction of 3’-single-strand DNA overhangs with ≥4 bp of homology requiring both the N-terminal AEP and C-terminal helicase domains. The proposed role for IEE in the novel IS excision mechanism is discussed.
Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation
Authors: Ge Yichen , Chen Xushen , Nan Nan , Bard Jonathan , Wu Fuguo , Yergeau Donald , Liu Tao , Wang Jie , Mu Xiuqian
Published: January 2023

How the diverse neural cell types emerge from multipotent neural progenitor cells during central nervous system development remains poorly understood. Recent scRNA-seq studies have delineated the developmental trajectories of individual neural cell types in many neural systems including the neural retina. Further understanding of the formation of neural cell diversity requires knowledge about how the epigenetic landscape shifts along individual cell lineages and how key transcription factors regulate these changes. In this study, we dissect the changes in the epigenetic landscape during early retinal cell differentiation by scATAC-seq and identify globally the enhancers, enriched motifs, and potential interacting transcription factors underlying the cell state/type specific gene expression in individual lineages. Using CUT&Tag, we further identify the enhancers bound directly by four key transcription factors, Otx2, Atoh7, Pou4f2 and Isl1, including those dependent on Atoh7, and uncover the sequential and combinatorial interactions of these factors with the epigenetic landscape to control gene expression along individual retinal cell lineages such as retinal ganglion cells (RGCs). Our results reveal a general paradigm in which transcription factors collaborate and compete to regulate the emergence of distinct retinal cell types such as RGCs from multipotent retinal progenitor cells (RPCs).
Cryptochromes suppress leaf senescence in response to blue light in Arabidopsis
Authors: Kozuka Toshiaki , Oka Yoshito , Kohzuma Kaori , Kusaba Makoto
Published: January 2023

The induction and progression of leaf senescence are effectively changed according to the light environment. The leaf senescence response is enhanced when plants are grown under a dense shade cast by neighboring vegetation. Although the fluence rate of the red and blue regions in the light spectrum is strongly attenuated under shade, photosensory mechanisms that underpin the blue light response are still unclear. In this study, we analyzed leaf senescence in response to blue light in Arabidopsis (Arabidopsis thaliana). We found that leaf senescence was promoted by the elimination of active phytochrome Pfr by pulsed far-red (FR) light, whereas irradiation with blue light suppressed leaf senescence in the wild type but not in the cryptochrome (CRY)-deficient mutant, cry1 cry2. Hence, two light-sensing modes contributed to the suppression of leaf senescence that was dependent on light spectrum features. First was the leaf senescence response to blue light, which was mediated exclusively by cryptochromes. Second was the phytochrome-mediated leaf senescence response to red/FR light. Physiological analysis of transgenic plants expressing green fluorescent protein (GFP)-tagged CRY2 revealed that photo-activation of cryptochromes was required to suppress leaf senescence in response to blue light. Transcriptomic analysis further uncovered the molecular and cellular processes involved in the regulation of leaf senescence downstream of cryptochromes. Furthermore, analysis of cryptochrome-downstream components indicated that ELONGATED HYPOCOTYL 5 (HY5) and PHYTOCHROME INTERACTING FACTOR (PIF) 4 and PIF5 were required for suppression and promotion of leaf senescence, respectively.
Natural overexpression of CAROTENOID CLEAVAGE DIOXYGENASE 4 in tomato alters carotenoid flux
Authors: Yoo Hee Ju , Chung Mi-Young , Lee Hyun-Ah , Lee Soo-Bin , Grandillo Silvana , Giovannoni James J , Lee Je Min
Published: January 2023

Carotenoids and apocarotenoids function as pigments and flavor volatiles in plants that enhance consumer appeal and offer health benefits. Tomato (Solanum lycopersicum.) fruit, especially those of wild species, exhibit a high degree of natural variation in carotenoid and apocarotenoid contents. Using positional cloning and an introgression line (IL) of Solanum habrochaites “LA1777', IL8A, we identified carotenoid cleavage dioxygenase 4 (CCD4) as the factor responsible for controlling the dark orange fruit color. CCD4b expression in ripe fruit of IL8A plants was ∼8,000 times greater than that in the wild type, presumably due to 5′ cis-regulatory changes. The ShCCD4b-GFP fusion protein localized in the plastid. Phytoene, ζ-carotene, and neurosporene levels increased in ShCCD4b-overexpressing ripe fruit, whereas trans-lycopene, β-carotene, and lutein levels were reduced, suggestive of feedback regulation in the carotenoid pathway by an unknown apocarotenoid. Solid-phase microextraction–gas chromatography–mass spectrometry analysis showed increased levels of geranylacetone and β-ionone in ShCCD4b-overexpressing ripe fruit coupled with a β-cyclocitral deficiency. In carotenoid-accumulating Escherichia coli strains, ShCCD4b cleaved both ζ-carotene and β-carotene at the C9–C10 (C9′–C10′) positions to produce geranylacetone and β-ionone, respectively. Exogenous β-cyclocitral decreased carotenoid synthesis in the ripening fruit of tomato and pepper (Capsicum annuum), suggesting feedback inhibition in the pathway. Our findings will be helpful for enhancing the aesthetic and nutritional value of tomato and for understanding the complex regulatory mechanisms of carotenoid and apocarotenoid biogenesis.
Toward the Identification of Distinct Phenotypes: Research Protocol for the Low Back Pain Biological, Biomechanical, and Behavioral (LB3P) Cohort Study and the BACPAC Mechanistic Research Center at the University of Pittsburgh
Authors: Vo Nam V , Piva Sara R , Patterson Charity G , McKernan Gina P , Zhou Leming , Bell Kevin M , Anderst William , Greco Carol M , Schneider Michael J , Delitto Anthony , Dicianno Brad E , Darwin Jessa , Sowa Gwendolyn A
Published: January 2023

As a member of the Back Pain Consortium (BACPAC), the University of Pittsburgh Mechanistic Research Center's research goal is to phenotype chronic low back pain using biological, biomechanical, and behavioral domains using a prospective, observational cohort study. Data will be collected from 1,000 participants with chronic low back pain according to BACPAC-wide harmonized and study-specific protocols. Participation lasts 12 months with one required in person baseline visit, an optional second in person visit for advanced biomechanical assessment, and electronic follow ups at months 1, 2, 3, 4, 5, 6, 9, and 12 to assess low back pain status and response to prescribed treatments. Behavioral data analysis includes a battery of patient-reported outcomes, social determinants of health, quantitative sensory testing, and physical activity. Biological data analysis includes omics generated from blood, saliva, and spine tissue. Biomechanical data analysis includes a physical examination, lumbopelvic kinematics, and intervertebral kinematics. The statistical analysis includes traditional unsupervised machine learning approaches to categorize participants into groups and determine the variables that differentiate patients. Additional analysis includes the creation of a series of decision rules based on baseline measures and treatment pathways as inputs to predict clinical outcomes. The characteristics identified will contribute to future studies to assist clinicians in designing a personalized, optimal treatment approach for each patient.
The Polls—Trends
Authors: Kudrnáč Aleš , Petrúšek Ivan
Published: January 2023

Income redistribution and changes in redistributive policies are highly contested issues that often have a bearing on societal debate and electoral competition. Using European Social Survey data, we trace trends in public attitudes toward income redistribution in 18 European countries from 2002 to 2019, a time period which included the Great Recession, the 2015 migrant crisis, and an increase in income inequality. Although attitudes toward income redistribution were relatively stable, trends presented by countries grouped by welfare regime display considerable variation both among countries and among welfare regimes. We also trace trends in public support for redistribution by income groups and gauge the strength of belief in meritocracy and egalitarianism. The level of redistribution support among middle-income residents is similar to redistribution support of low-income residents, most notably in post-communist and social-democratic regimes. While egalitarianism is most widespread in the Mediterranean regime, meritocracy is most common in liberal and conservative regimes.
Digital Administrative Burdens: An Agenda for Analyzing the Citizen Experience of Digital Bureaucratic Encounters
Authors: Peeters Rik
Published: January 2023

Innovations in digital government are changing state–citizen interactions. While often seen as means to increase government efficiency and reduce compliance costs for citizens, a growing body of literature suggests citizens may also experience administrative burdens in such interactions. This article aims to provide some cohesion to the existing research and makes three specific contributions. First, it carves out a conceptual common ground by identifying digital administrative burdens and digital bureaucratic encounters as specific objects of study. Second, automated administrative decision making, digital interactions, and data-assisted decision making are identified as contemporary practices of particular relevance for future studies on the intersection of digital government and administrative burden. Studies suggest learning costs and psychological costs may be especially prevalent in digital bureaucratic encounters and that they often have distributive effects. Third, the article concludes with the formulation of several research themes for the further development of the field.
Extended delta-map: A map-based foreground removal method for CMB polarization observations
Authors: Minami Yuto , Ichiki Kiyotomo
Published: January 2023

In order to extract information about inflationary gravitational waves using B-mode patterns of cosmic microwave polarization anisotropy, we need to remove the foreground radiation from the Milky Way. In our previous delta-map method for foreground removal, the number of observation bands was limited to the number of parameters of the assumed foreground model, and therefore it was difficult to improve the sensitivity by increasing the number of observation bands. Here, we extend the previous method so that it can be adapted to an arbitrary number of observation bands. Using parametric likelihood and realistic foreground and CMB simulations, we show that our method can increase the sensitivity to the tensor-to-scalar ratio r without inducing any significant bias.
Entanglement bipartitioning and tree tensor networks
Authors: Okunishi Kouichi , Ueda Hiroshi , Nishino Tomotoshi
Published: January 2023

We propose the entanglement bipartitioning approach to design an optimal network structure of the tree tensor network (TTN) for quantum many-body systems. Given an exact ground-state wavefunction, we perform sequential bipartitioning of spin-cluster nodes so as to minimize the mutual information or the maximum loss of the entanglement entropy associated with the branch to be bipartitioned. We demonstrate that entanglement bipartitioning of up to 16 sites gives rise to nontrivial tree network structures for S = 1/2 Heisenberg models in one and two dimensions. The resulting TTNs enable us to obtain better variational energies, compared with standard TTNs such as the uniform matrix product state and perfect binary tree tensor network.
Dose–response relationships of tea and coffee consumption with gout: a prospective cohort study in the UK Biobank
Authors: Guo Huangda , Wang Siyue , Peng Hexiang , Wang Mengying , Li Liming , Huang Jie , Wu Tao
Published: January 2023

Objectives

The association of tea or coffee consumption with gout is inconsistently reported. Few prospective studies have explored their dose–response relationship. Therefore, we aimed to quantitatively investigate the association between tea, coffee and the risk of developing gout.

Methods

The study included 447 658 participants in the UK Biobank who were initially free of gout. Tea and coffee consumption were assessed at baseline. We used Cox proportional hazards models to estimate the associations between tea/coffee consumption and incident gout, with restricted cubic spline added to the Cox models to evaluate the dose–response relationships.

Results

During a median follow-up period of 13.42 years, we recorded 3,053 gout cases. The associations between tea, coffee and gout were nonlinear, with a significant reduction in the risk by ∼ six cups/day of tea and three cups/day of coffee. Compared with those who were not tea and coffee drinkers, those who consumed >6 cups/day of tea or coffee were associated with 23% (HR 0.77, 95% CI, 0.66, 0.91) and 40% (HR 0.60, 95% CI, 0.47, 0.77) lower risks of gout, respectively, and both caffeinated and decaffeinated coffee consumption were associated with a decreased risk. Moreover, hyperuricaemia may modify the association between coffee and gout. Compared with non-coffee consumers with hyperuricaemia, those with ≥4 cups/day coffee intake without hyperuricaemia had the lowest risk (HR 0.34, 95% CI, 0.28, 0.41).

Conclusion

Consumption of tea or coffee had a strong nonlinear association in gout risk reduction. Hyperuricaemia status had a potential effect modification on the association of coffee intake with gout.
Mother–child neural synchronization is time linked to mother–child positive affective state matching
Authors: Morgan Judith K , Santosa Hendrik , Conner Kaetlyn K , Fridley Rachel M , Forbes Erika E , Iyengar Satish , Joseph Heather M , Huppert Theodore J
Published: January 2023

In the first years of life, in which self-regulation occurs via external means, mother–child synchronization of positive affect (PA) facilitates regulation of child homeostatic systems. Mother–child affective synchrony may contribute to mother–child synchronization of neural systems, but limited research has explored this possibility. Participants were 41 healthy mother–child dyads (56% girls; Mage = 24.76 months; s.d. = 8.77 months, Range = 10–42 months). Mothers’ and children’s brain activities were assessed simultaneously using near-infrared spectroscopy while engaging in dyadic play. Mother and child PA during play were coded separately to characterize periods in which mothers and children (i) matched on high PA, (ii) matched on low/no PA or (iii) showed a mismatch in PA. Models evaluated moment-to-moment correlations between affective matching and neural synchrony in mother–child dyads. Greater positive affective synchrony, in which mother and child showed similarly high levels of PA but not similarly low levels of PA, was related to greater synchrony in medial and lateral frontal and temporoparietal regions. Age moderated associations between mother and child neural activities but only during moments of high PA state matching. Positive, synchronous mother–child interactions may foster greater neural responding in affective and social regions important for self-regulation and interpersonal bonds.
Mouse Model of Spinal Cord Hypoperfusion with Immediate Paralysis Caused by Endovascular Repair of Thoracic Aortic Aneurysm
Authors: Kelani Hesham , Corps Kara , Mikula Sarah , Fisher Lesley C. , Shalaan Mahmoud T. , Sturgill Sarah , Ziolo Mark T. , Abdel-Rasoul Mahmoud , Basso D. Michele , Awad Hamdy
Published: January 2023

Background

A clinically relevant mouse model of thoracic endovascular aortic repair–induced ischemic spinal cord injury has been lacking since the procedure was first employed in 1991. The hypothesis was that ligation of mouse intercostal arteries would simulate thoracic endovascular aortic repair–induced ischemic spinal cord injury and behavioral deficit. The aim was to create a mouse model of thoracic endovascular aortic repair–induced spinal cord hypoperfusion by ligating five pairs of mouse intercostal vessels.

Methods

Mice were divided into sham (n = 53) and ligation (n = 60) groups. The procedures called for double ligation of three pairs and single ligation of two pairs of thoracic intercostal arteries in adult C57BL/6 mice. A laser Doppler probe was used in vivo on the spinal cords and intercostal arteries to document the extent of arterial ligation and spinal cord hypoperfusion. The Basso Mouse Scale for Locomotion, histological studies, and electron microscopy demonstrated postligation locomotive and histopathological changes.

Results

Ligation induced a significant and instantaneous drop in blood flow in the intercostal arteries (% change; mean = −63.81; 95% CI, −72.28 to −55.34) and the thoracic spinal cord (% change; mean = −68.55; 95% CI, −80.23 to −56.87). Paralysis onset was immediate and of varying degree, with behavioral deficit stratified into three groups: 9.4% exhibited severe paralysis, 37.5% moderate paralysis, and 53.1% mild paralysis at day 1 (n = 32; P < 0.001). Mild and moderate paralysis was transient, gradually improving over time. Severe paralysis showed no improvement and exhibited a higher mortality rate (83%; n = 15 of 18) compared to moderately (33%; n = 6 of 18) and mildly (24%; n = 6 of 25) paralyzed mice (P < 0.001). The overall ligation group survival rate (84%; n = 46 of 55) was significantly lower than the sham group (100%; n = 48 of 48) with P = 0.003.

Conclusions

The mouse model generates reproducible spinal cord hypoperfusion and accompanying histopathological ischemic spinal cord damage. The resulting anatomical changes and variable behavioral deficits mimic the variability in radiological and clinical findings in human patients.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Surgical Informed Consent
Authors: Melucci Alexa D. , Erlick Mariah R. , Loria Anthony , Russell Marcia M. , Temple Larissa K. , Poles Gabriela C.
Published: January 2023

Objectives:

Physician-facing decision support tools facilitate shared decision-making (SDM) during informed consent, but it is unclear whether they are comprehensive in the domains they measure. In this scoping review, we aimed to (1) identify the physician-facing tools used during SDM; (2) assess the patient-centered domains measured by these tools; (3) determine whether tools are available for older adults and for use in various settings (elective vs. emergent); and (4) characterize domains future tools should measure.

Methods:

Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews, Embase, Medline, and Web of Science were queried for articles published between January 2000 and September 2022. Articles meeting inclusion criteria underwent title and abstract review. Eligible studies underwent data abstraction by two reviewers.

Results:

Of 4365 articles identified, 160 were eligible. Tools to aid in surgical SDM focus on elective procedures (79%) and the outpatient setting (71%). Few tools are designed for older adults (5%) or for nonelective procedures (9%). Risk calculators were most common, followed by risk indices, prognostic nomograms, and communication tools. Of the domains measured, prognosis was more commonly measured (85%), followed by alternatives (28%), patient goals (36%), and expectations (46%). Most tools represented only one domain (prognosis, 33.1%) and only 6.7% represented all four domains.

Conclusions and Implications:

Tools to aid in the surgical SDM process measure short-term prognosis more often than patient-centered domains such as long-term prognosis, patient goals, and expectations. Further research should focus on communication tools, the needs of older patients, and use in diverse settings.