bluuebunny/crossref_metadata_2025 huggingface dataset:
The fundamentals of Lyman α exoplanet transits
Authors: Owen James E , Murray-Clay Ruth A , Schreyer Ethan , Schlichting Hilke E , Ardila David , Gupta Akash , Loyd R O Parke , Shkolnik Evgenya L , Sing David K , Swain Mark R
Published: November 2022

Lyman α transits have been detected from several nearby exoplanets and are one of our best insights into the atmospheric escape process. However, due to ISM absorption, we typically only observe the transit signature in the blue-wing, making them challenging to interpret. This challenge has been recently highlighted by non-detections from planets thought to be undergoing vigorous escape. Pioneering 3D simulations have shown that escaping hydrogen is shaped into a cometary tail receding from the planet. Motivated by this work, we develop a simple model to interpret Lyman α transits. Using this framework, we show that the Lyman α transit depth is primarily controlled by the properties of the stellar tidal field rather than details of the escape process. Instead, the transit duration provides a direct measurement of the velocity of the planetary outflow. This result arises because the underlying physics is the distance a neutral hydrogen atom can travel before it is photoionized in the outflow. Thus, higher irradiation levels, expected to drive more powerful outflows, produce weaker, shorter Lyman α transits because the outflowing gas is ionized more quickly. Our framework suggests that the generation of energetic neutral atoms may dominate the transit signature early, but the acceleration of planetary material produces long tails. Thus, Lyman α transits do not primarily probe the mass-loss rates. Instead, they inform us about the velocity at which the escape mechanism is ejecting material from the planet, providing a clean test of predictions from atmospheric escape models.
A new technique to isolate kinematically anomalous gas in H i data cubes
Authors: Randriamiarinarivo N , Elson E C , Baker A J
Published: November 2022

H i line observations of nearby galaxies often reveal the presence of extraplanar and/or kinematically anomalous gas that deviates from the general circular flow. In this work, we study the dependence of kinematically anomalous H i gas in galaxies taken from the simba cosmological simulation on galaxy properties such as H i mass fraction, specific star formation rate, and local environmental density. To identify kinematically anomalous gas, we use a simple yet effective decomposition method to separate it from regularly rotating gas in the galactic disc; this method is well-suited for application to observational data sets but has been validated here using the simulation. We find that at fixed atomic gas mass fraction, the anomalous gas fraction increases with the specific star formation rate. We also find that the anomalous gas fraction does not have a significant dependence on a galaxy’s environment. Our decomposition method has the potential to yield useful insights from future H i surveys.
MASCOT: molecular gas depletion times and metallicity gradients – evidence for feedback in quenching active galaxies
Authors: Bertemes C , Wylezalek D , Albán M , Aravena M , Baker W M , Cazzoli S , Cicone C , Martín S , Schimek A , Wagg J , Wang W
Published: November 2022

We present results from the first public data release of the MaNGA-ARO Survey of CO Targets (MASCOT), focusing our study on galaxies whose star formation rates and stellar masses place them below the ridge of the star-forming main sequence. In optically selected type 2 AGN/low-ionization nuclear emission regions (LINERs)/Composites, we find an empirical relation between gas-phase metallicity gradients ∇Z and global molecular gas depletion times $t_{\rm dep} = M_{\rm H_2} /{\rm SFR}$ with ‘more quenched’ systems showing flatter/positive gradients. Our results are based on the O3N2 metallicity diagnostic (applied to star-forming regions within a given galaxy), which was recently suggested to also be robust against emission by diffuse ionized gas (DIG) and LINERs. We conduct a systematic investigation into possible drivers of the observed ∇Z − tdep relation (ouflows, gas accretion, in situ star formation, mergers, and morphology). We find a strong relation between ∇Z or tdep and centralized outflow strength traced by the [O iii] velocity broadening. We also find signatures of suppressed star formation in the outskirts in AGN-like galaxies with long depletion times and an enhancement of metals in the outer regions. We find no evidence of inflows impacting the metallicity gradients, and none of our results are found to be significantly affected by merger activity or morphology. We thus conclude that the observed ∇Z–tdep relation may stem from a combination of metal redistribution via weak feedback, and a connection to in situ star formation via a resolved mass-metallicity–SFR relation.
Collisional excitation of hyperfine levels of OH by hydrogen atoms
Authors: Dagdigian Paul J
Published: November 2022

Observations of transitions between the hyperfine levels of the hydroxyl radical (OH) can provide crucial information on the physical conditions in interstellar clouds. Accurate modelling of the spectra requires calculated rate coefficients for the excitation of OH by H atoms, which is often present in molecular clouds in addition to the dominant H2 molecule. In this work, rate coefficients for the (de-)excitation of hyperfine levels of OH through collisions with hydrogen atoms are presented. In previous work, nuclear-spin-free scattering calculations were carried out; these took account of the fact that four electronic states (1A′, 1A″, 3A′, and 3A″) arise from the interaction of OH(X2Π) with H(2S). Because of the deep H2O($\tilde{X}^1A^{\prime }$) well, inelastic transitions can occur through direct collisions or by formation and decay of a collision complex. The rates of collision-induced hyperfine transitions were computed by the recoupling method and the MJ randomization approximations, respectively. These data will be useful in astrophysical models of OH excitation.
Photochemical escape of atomic C, N, and O during the 2018 global dust storm on Mars
Authors: Huang Xu , Gu Hao , Cui Jun , Wu Xiaoshu , Sun Mingyang
Published: November 2022

Dust storm is an important meteorological phenomenon on Mars. By modifying the structure of the Martian atmosphere and ionosphere, it plays an indispensable role in the Martian photochemistry and atmospheric loss. This study is devoted to evaluating the effects of the 2018 global dust storm (GDS) on the photochemical escape of atomic C, N, and O on Mars based on multi-instrument measurements made by the Mars Atmosphere and Volatile EvolutioN spacecraft. The data set is divided into the non-dusty and dusty stages, for which the hot atom production rates from a variety of channels are calculated. A one-dimensional Monte Carlo model is then constructed to obtain the escape probability profile for each channel. By combining the above results, we derive the photochemical escape rates, both prior to and during the GDS. Our calculations suggest that the GDS-induced C, N, and O escape is generally reduced by ∼30–$40{{\%}}$ relative to the quiet, pre-GDS state, in direct contrast to the well-known result of GDS-induced strong enhancement of atomic H escape. We further propose that the GDS-induced variation of photochemical escape essentially reflects the competition between two effects: the modification of hot atom production (enhancement for photodissociation or reduction for dissociative recombination) driven by the variation of the background atmosphere and the reduction of escape probability due to atmospheric expansion. During the GDS, the latter is usually more effective and responsible for the overall reduction of photochemical escape on Mars.
Massive star cluster origin for the galactic cosmic ray population at very-high energies
Authors: Vieu T , Reville B
Published: November 2022

We demonstrate that supernova remnant (SNR) shocks embedded within massive star clusters can reproduce both the cosmic-ray proton and all-particle spectra measured in the vicinity of the Earth up to hundreds of peta-electronvolts (PeV). We model two classes of massive star clusters. The first population are ‘loose clusters’ that do not power a collective wind termination shock. SNR shocks then expand in a low-density and weakly magnetized medium, and this population mainly contributes up to the ‘knee’ of the CR spectrum around 1 PeV. The second population are young compact clusters, which are powerful and compact enough to sustain a collective wind outflow. SNR shocks then expand from the cluster into the strongly magnetized wind and accelerate nuclei up to ultra-high energies. This population, representing only about 15 per cent of all Galactic massive star clusters, nevertheless dominates the spectrum between ∼1 and 100 PeV. While these two components alone can reproduce the shape of the CR spectrum up to hundreds of PeV, adding a light subankle extragalactic component motivated by composition and anisotropy measurements, allows to reproduce the spectrum up to the highest energies. Fitting parameters are systematically linked to physical variables whose values are in line with theoretical expectations.
Overlap syndrome involving anti-OJ antibody-positive polymyositis, systemic lupus erythematosus and Sjögren’s syndrome: A case report and literature review
Authors: Mizuhashi Yumiko , Hirata Shinya , Sakata Komei , Miyagawa Eiko , Iwakura Mikako , Murai Masayuki , Sasai Tsuneo , Matsuoka Masao
Published: November 2022

Anti-OJ antibody is relatively rarely detected in patients with the anti-synthetase syndrome, which is polymyositis (PM)/dermatomyositis (DM) with anti-aminoacyl transfer ribonucleic acid (RNA) synthetase antibodies. There have been few case reports of anti-OJ antibody-positive PM/DM complicated by other connective tissue disorders. Herein, we report the case of a 33-year-old woman who was admitted to our hospital with fever, muscle weakness, and dyspnoea on exertion. She was diagnosed with anti-OJ antibody-positive PM, overlapping systemic lupus erythematosus, and Sjögren’s syndrome (SS). Her symptoms and clinical findings improved after treatment with prednisolone 1 mg/kg/day without immunosuppressive agents. This is the first case of overlap syndrome with anti-OJ antibody-positive PM, systemic lupus erythematosus, and Sjögren’s syndrome.
The UCSC Genome Browser database: 2023 update
Authors: Nassar Luis R , Barber Galt P , Benet-Pagès Anna , Casper Jonathan , Clawson Hiram , Diekhans Mark , Fischer Clay , Gonzalez Jairo Navarro , Hinrichs Angie S , Lee Brian T , Lee Christopher M , Muthuraman Pranav , Nguy Beagan , Pereira Tiana , Nejad Parisa , Perez Gerardo , Raney Brian J , Schmelter Daniel , Speir Matthew L , Wick Brittney D , Zweig Ann S , Haussler David , Kuhn Robert M , Haeussler Maximilian , Kent W James
Published: November 2022

The UCSC Genome Browser (https://genome.ucsc.edu) is an omics data consolidator, graphical viewer, and general bioinformatics resource that continues to serve the community as it enters its 23rd year. This year has seen an emphasis in clinical data, with new tracks and an expanded Recommended Track Sets feature on hg38 as well as the addition of a single cell track group. SARS-CoV-2 continues to remain a focus, with regular annotation updates to the browser and continued curation of our phylogenetic sequence placing tool, hgPhyloPlace, whose tree has now reached over 12M sequences. Our GenArk resource has also grown, offering over 2500 hubs and a system for users to request any absent assemblies. We have expanded our bigBarChart display type and created new ways to visualize data via bigRmsk and dynseq display. Displaying custom annotations is now easier due to our chromAlias system which eliminates the requirement for renaming sequence names to the UCSC standard. Users involved in data generation may also be interested in our new tools and trackDb settings which facilitate the creation and display of their custom annotations.
3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells
Authors: Jodkowska Karolina , Pancaldi Vera , Rigau Maria , Almeida Ricardo , Fernández-Justel José M , Graña-Castro Osvaldo , Rodríguez-Acebes Sara , Rubio-Camarillo Miriam , Carrillo-de Santa Pau Enrique , Pisano David , Al-Shahrour Fátima , Valencia Alfonso , Gómez María , Méndez Juan
Published: November 2022

In mammalian cells, chromosomal replication starts at thousands of origins at which replisomes are assembled. Replicative stress triggers additional initiation events from ‘dormant’ origins whose genomic distribution and regulation are not well understood. In this study, we have analyzed origin activity in mouse embryonic stem cells in the absence or presence of mild replicative stress induced by aphidicolin, a DNA polymerase inhibitor, or by deregulation of origin licensing factor CDC6. In both cases, we observe that the majority of stress-responsive origins are also active in a small fraction of the cell population in a normal S phase, and stress increases their frequency of activation. In a search for the molecular determinants of origin efficiency, we compared the genetic and epigenetic features of origins displaying different levels of activation, and integrated their genomic positions in three-dimensional chromatin interaction networks derived from high-depth Hi-C and promoter-capture Hi-C data. We report that origin efficiency is directly proportional to the proximity to transcriptional start sites and to the number of contacts established between origin-containing chromatin fragments, supporting the organization of origins in higher-level DNA replication factories.
Arabidopsis EXECUTER1 interacts with WRKY transcription factors to mediate plastid-to-nucleus singlet oxygen signaling
Authors: Li Yuhong , Liu Hanhong , Ma Tingting , Li Jialong , Yuan Jiarui , Xu Yong-Chao , Sun Ran , Zhang Xinyu , Jing Yanjun , Guo Ya-Long , Lin Rongcheng
Published: November 2022

Chloroplasts produce singlet oxygen (1O2), which causes changes in nuclear gene expression through plastid-to-nucleus retrograde signaling to increase plant fitness. However, the identity of this 1O2-triggered pathway remains unclear. Here, we identify mutations in GENOMES UNCOUPLED4 (GUN4) and GUN5 as suppressors of phytochrome-interacting factor1 (pif1) pif3 in regulating the photo-oxidative response in Arabidopsis thaliana. GUN4 and GUN5 specifically interact with EXECUTER1 (EX1) and EX2 in plastids, and this interaction is alleviated by treatment with Rose Bengal (RB) or white light. Impaired expression of GUN4, GUN5, EX1, or EX2 leads to insensitivity to excess light and overexpression of EX1 triggers photo-oxidative responses. Strikingly, upon light irradiation or RB treatment, EX1 transiently accumulates in the nucleus and the nuclear fraction of EX1 shows a similar molecular weight as the plastid-located protein. Point mutagenesis analysis indicated that nuclear localization of EX1 is required for its function. EX1 acts as a transcriptional co-activator and interacts with the transcription factors WRKY18 and WRKY40 to promote the expression of 1O2-responsive genes. This study suggests that EX1 may act in plastid-to-nucleus signaling and establishes a 1O2-triggered retrograde signaling pathway that allows plants adapt to changing light environments during chloroplast development.
CO interacts with JAZ repressors and bHLH subgroup IIId factors to negatively regulate jasmonate signaling in Arabidopsis seedlings
Authors: Han Xiao , Kui Mengyi , Xu Tingting , Ye Jingwen , Du Jiancan , Yang Milian , Jiang Yanjuan , Hu Yanru
Published: November 2022

CONSTANS (CO) is a master flowering-time regulator that integrates photoperiodic and circadian signals in Arabidopsis thaliana. CO is expressed in multiple tissues, including young leaves and seedling roots, but little is known about the roles and underlying mechanisms of CO in mediating physiological responses other than flowering. Here, we show that CO expression is responsive to jasmonate. CO negatively modulated jasmonate-imposed root-growth inhibition and anthocyanin accumulation. Seedlings from co mutants were more sensitive to jasmonate, whereas overexpression of CO resulted in plants with reduced sensitivity to jasmonate. Moreover, CO mediated the diurnal gating of several jasmonate-responsive genes under long-day conditions. We demonstrate that CO interacts with JASMONATE ZIM-DOMAIN (JAZ) repressors of jasmonate signaling. Genetic analyses indicated that CO functions in a CORONATINE INSENSITIVE1 (COI1)-dependent manner to modulate jasmonate responses. Furthermore, CO physically associated with the basic helix-loop-helix (bHLH) subgroup IIId transcription factors bHLH3 and bHLH17. CO acted cooperatively with bHLH17 in suppressing jasmonate signaling, but JAZ proteins interfered with their transcriptional functions and physical interaction. Collectively, our results reveal the crucial regulatory effects of CO on mediating jasmonate responses and explain the mechanism by which CO works together with JAZ and bHLH subgroup IIId factors to fine-tune jasmonate signaling.
The noncoding RNA HIDDEN TREASURE 1 promotes phytochrome B-dependent seed germination by repressing abscisic acid biosynthesis
Authors: Wang Yuqiu , Fan Yangyang , Fan De , Zhou Xiaoli , Jiao Yuntong , Deng Xing Wang , Zhu Danmeng
Published: November 2022

Light is a major environmental factor for seed germination. Red light-activated phytochrome B (phyB) promotes seed germination by modulating the dynamic balance of two phytohormones, gibberellic acid (GA) and abscisic acid (ABA). How phyB modulates ABA biosynthesis after perceiving a light signal is not yet well understood. Here, we identified the noncoding RNA HIDDEN TREASURE 1 (HID1) as a repressor of ABA biosynthesis acting downstream of phyB during Arabidopsis thaliana seed germination. Loss of HID1 function led to delayed phyB-dependent seed germination. Photoactivated phyB promoted the accumulation of HID1 in the radicle within 48 h of imbibition. Our transcriptomics analysis showed that HID1 and phyB co-regulate the transcription of a common set of genes involved in ABA and GA metabolism. Through a forward genetic screen, we identified three ABA biosynthesis genes, ABA DEFICIENT 1 (ABA1), ABA2, and ABA3, as suppressors of HID1. We further demonstrated that HID1 directly inhibits the transcription of 9-CIS-EPOXYCAROTENOID DIOXYGENASE (NCED9), a gene encoding a key rate-limiting enzyme of ABA biosynthesis. HID1 interacts with ARABIDOPSIS TRITHORAX-RELATED7 (ATXR7), an H3K4me3 methyltransferase, inhibiting its occupancy and H3K4me3 modification at the NCED9 locus. Our study reveals a nuclear mechanism of phyB signaling transmitted through HID1 to control the internal homeostasis of ABA and GA, which gradually optimizes the transcriptional network during seed germination.
Endosperm cellularization failure induces a dehydration-stress response leading to embryo arrest
Authors: Xu Wenjia , Sato Hikaru , Bente Heinrich , Santos-González Juan , Köhler Claudia
Published: November 2022

The endosperm is a nutritive tissue supporting embryo growth in flowering plants. Most commonly, the endosperm initially develops as a coenocyte (multinucleate cell) and then cellularizes. This process of cellularization is frequently disrupted in hybrid seeds generated by crosses between different flowering plant species or plants that differ in ploidy, resulting in embryo arrest and seed lethality. The reason for embryo arrest upon cellularization failure remains unclear. In this study, we show that triploid Arabidopsis thaliana embryos surrounded by uncellularized endosperm mount an osmotic stress response that is connected to increased levels of abscisic acid (ABA) and enhanced ABA responses. Impairing ABA biosynthesis and signaling aggravated triploid seed abortion, while increasing endogenous ABA levels as well as the exogenous application of ABA-induced endosperm cellularization and suppressed embryo growth arrest. Taking these results together, we propose that endosperm cellularization is required to establish dehydration tolerance in the developing embryo, ensuring its survival during seed maturation.
Weather and Crime—Cautious evidence from South Africa
Authors: Ankel-Peters Jörg , Bruederle Anna , Roberts Gareth
Published: November 2022

South Africa has one of the highest crime rates in the world. This paper examines the effect of weather shocks on various types of crime. Using a 12-year panel data set at a monthly resolution on the police ward level, we observe a short-term effect of temperatures on violent crime. Furthermore, we find evidence for the medium-term effect of weather on crime via droughts. Yet, effect sizes are subtle in both cases and we also emphasize often neglected but well-documented limitations to the interpretability of weather data and weather-induced mechanisms. Recognizing these limitations, we conclude with a cautious interpretation of our findings to inform police deployment strategies.
Is the relationship between deprivation and outcomes in rheumatoid arthritis mediated by body mass index? A longitudinal cohort study
Authors: Witkam Rozemarijn , Gwinnutt James M , Humphreys Jennifer , Verstappen Suzanne M M ,   RAMS Co-Investigators, Adebajo Ade , Ahmed Khalid , Al-Ansari Atheer , Amarasena Roshan , Bukhari Marwan , Callan Margaret , Chelliah Easwaradhas G , Chinoy Hector , Cooper Annie , Dasgupta Bhaskar , Davis Martin , Galloway James , Gough Andrew , Green Michael , Gullick Nicola , Hamilton Jennifer , Hassan Waji , Hider Samantha , Hyrich Kimme , Kamath Sanjeet , Knight Susan , Lane Suzanne , Lee Martin , Levy Sarah , Macphie Lizzy , Marguerie Christopher , Marshall Tarnya , Mathews Catherine , McKenna Frank , Naz Sophia , Perry Mark , Pollard Louise , Quilty Brian , Robertson Lindsay , Roy Dipak , Sanders Paul , Saravanan Vadivelu , Scott David , Smith Gillian , Smith Richard , Symmons Deborah , Teh Lee-Suan , Viner Nick
Published: November 2022

Objectives

To understand the relationships between deprivation and obesity with self-reported disability and disease activity in people with RA, and to determine whether BMI mediates the relationship between area-level deprivation and these outcomes.

Methods

Data came from the Rheumatoid Arthritis Medication Study (RAMS), a 1-year multicentre prospective observational cohort of people with RA recruited from rheumatology centres across England commencing MTX for the first time. A total of 1529 and 1626 people were included who had a baseline and at least one follow-up measurement at 6 or 12 months of HAQ—Disability Index (HAQ-DI) and DAS in 28 joints (DAS28), respectively. Linear mixed models estimated the associations of deprivation and obesity with repeated measures HAQ-DI and DAS28. Causal mediation analyses estimated the mediating effect of BMI on the relationship between deprivation and RA outcomes.

Results

Higher deprivation and obesity were associated with higher disability [adjusted regression coefficients highest vs lowest deprivation fifths 0.32 (95% CI 0.19, 0.45); obesity vs no obesity 0.13 (95% CI 0.06, 0.20)] and higher disease activity [adjusted regression coefficients highest vs lowest deprivation fifths 0.34 (95% CI 0.11, 0.58); obesity vs no obesity 0.17 (95% CI 0.04, 0.31)]. BMI mediated part of the association between higher deprivation and self-reported disability (14.24%) and DAS (17.26%).

Conclusions

People with RA living in deprived areas have a higher burden of disease, which is partly mediated through obesity. Weight-loss strategies in RA could be better targeted towards those living in deprived areas.
High risk of stroke in ANCA-associated vasculitis—a population-based study
Authors: Tabakovic Dennis , Smith Rona , Jayne David , Mohammad Aladdin J
Published: November 2022

Objective

To determine the incidence rate, predictors and outcome of stroke in a population-based cohort of individuals with ANCA-associated vasculitis (AAV).

Methods

The study included 325 patients diagnosed with AAV from 1997 through 2016 in a defined geographic area of Sweden. Patients who suffered a stroke were identified from Riksstroke, a national Swedish stroke register established in 1994, and the Skåne Healthcare Register (SHR), which includes data for all inhabitants of Skåne since 1998. Case record review was carried out to confirm the diagnosis of stroke in AAV patients identified in the SHR. The incidence rate of stroke was calculated per 1000 person-years of follow-up. Using data from the Swedish general population, the standardized incidence ratio (SIR) of stroke was estimated. Cox regression analysis was utilized to investigate survival and predictors of stroke.

Results

Twenty-five subjects (8%) suffered a stroke during 2206 person-years of follow-up. The incidence rate of stroke in AAV was 11.3/1000 person-years (95% CI 6.9, 15.8). Patients with AAV showed an increased risk of stroke compared with the general population [SIR 1.85 (95% CI 1.27, 2.59)], with a greater risk for those <65 years of age [SIR 3.19 (95% CI 1.53, 5.88)]. Higher platelet count at AAV diagnosis was an independent predictor of stroke [hazard ratio 1.14 (95% CI 1.00, 1.29)]. There were no differences in survival or other outcome measures between AAV patients with and without stroke.

Conclusions

The incidence rate of stroke in AAV is higher than in the general population. High platelet count at AAV diagnosis was associated with an increased risk of stroke.
Early Childhood Neurocognition in Relation to Middle Childhood Psychotic Experiences in Children at Familial High Risk of Schizophrenia or Bipolar Disorder and Population-Based Controls: The Danish High Risk and Resilience Study
Authors: Knudsen Christina Bruun , Hemager Nicoline , Jepsen Jens Richardt Møllegaard , Gregersen Maja , Greve Aja Neergaard , Andreassen Anna Krogh , Veddum Lotte , Brandt Julie Marie , Krantz Mette Falkenberg , Søndergaard Anne , Burton Birgitte Klee , Thorup Anne Amalie Elgaard , Nordentoft Merete , Lambek Rikke , Mors Ole , Bliksted Vibeke Fuglsang
Published: November 2022

Background and Hypothesis

Familial high-risk (FHR) studies examining longitudinal associations between neurocognition and psychotic experiences are currently lacking. We hypothesized neurocognitive impairments at age 7 to be associated with increased risk of psychotic experiences from age 7 to 11 in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and population-based controls (PBC), and further, impaired functioning in some neurocognitive functions to be associated with greater risk of psychotic experiences in children at FHR-SZ or FHR-BP relative to PBC.

Study Design

Neurocognition was assessed at age 7 (early childhood) and psychotic experiences from age 7 to 11 (middle childhood) in 449 children from the Danish High Risk and Resilience Study. The neurocognitive assessment covered intelligence, processing speed, attention, visuospatial and verbal memory, working memory, and set-shifting. Psychotic experiences were assessed through face-to-face interviews with the primary caregiver and the child.

Study Results

Set-shifting impairments at age 7 were associated with greater risk of psychotic experiences from age 7 to 11 in children at FHR-SZ. Children at FHR-BP and PBC showed no differential associations. Working memory and visuospatial memory impairments were related to increased risk of psychotic experiences across the cohort. However, adjusting for concurrent psychopathology attenuated these findings.

Conclusions

Early childhood neurocognitive impairments are risk markers of middle childhood psychotic experiences, of which impaired set-shifting appears to further increase the risk of psychotic experiences in children at FHR-SZ. More research is needed to examine longitudinal associations between neurocognitive impairments and psychotic experiences in FHR samples.
Does offensive patent insurance promote corporate innovation? Evidence from a quasi-experiment
Authors: Wu Ying , Zhang Yi
Published: November 2022

This article empirically investigates the impact of offensive patent insurance on corporate innovation based on China’s patent insurance policy. We find that offensive patent insurance promotes corporate innovation. The result is robust to a battery of sensitivity tests and is more prominent for firms located in regions with more efficiency in handling patent infringement cases, for small enterprises, for firms located in regions with better implementation of the insurance policy, and for firms with less complex technologies. In addition, we observe that offensive patent insurance promotes corporate innovation by stimulating corporate Research and Development (R&D) investment. Furthermore, we find that offensive patent insurance promotes radical innovation and incremental innovation and has an insignificant negative effect on appearance innovation, suggesting that offensive patent insurance leads enterprises to invest more resources in the development of innovations with higher market value. Our study suggests that offensive patent insurance is an important tool to promote corporate innovation.
Relative contributions to patient effective dose in SPECT-CT hybrid imaging
Authors: Dixon Jonathan , Dennis Jen
Published: November 2022

Medical imaging using ionising radiation, while commonplace, has an associated risk of cancer induction. In trying to manage this risk it is beneficial to be able to quantify it through the use of effective dose. Estimates of effective dose resulting from radiopharmaceutical administration are well established in published data but the equivalent data for the computed tomography (CT) component of nuclear medicine hybrid imaging is less well-known. This study aims to estimate the absolute and relative contributions to effective dose from radiopharmaceutical and CT components of common single photon emission computed tomography (SPECT)-CT procedures. Using patient dose-audit data from three SPECT-CT systems we estimated the effective dose resulting from radiopharmaceutical administration by scaling the published effective dose data according to administered activity. The corresponding effective dose resulting from the CT component was estimated using the ImPACT CT dosimetry tool. Absolute effective dose from radiopharmaceutical administrations ranged from 0.2 (Tc-99m colloid head and neck sentinel lymph node imaging) to 14.2 mSv (dual-isotope Tc-99m sestamibi/I-123 sodium iodide parathyroid imaging). Effective dose from the CT components ranged from 0.3 (Tl-201 chloride brain scans – scan range covering the brain) to 4.4 mSv (Tc-99m HYNIC Ty3-Octreotide scans which use a scan range from the top of the brain to bottom of pelvis). Relative contributions (radiopharmaceutical/CT) ranged from 11/89 (Tc-99m colloid head and neck sentinel lymph node imaging) to 98/2% (Tl-201 chloride brain scans). There is a wide range of effective dose from radiopharmaceutical and CT components of hybrid imaging and both aspects can benefit from optimisation efforts, with the largest benefit coming from the CT components.
A multi-omics atlas of the human retina at single-cell resolution
Authors: Liang Qingnan , Cheng Xuesen , Wang Jun , Owen Leah , Shakoor Akbar , Lillvis John L. , Zhang Charles , Farkas Michael , Kim Ivana K. , Li Yumei , DeAngelis Margaret , Chen Rui
Published: November 2022

Cell classes in the human retina are highly heterogeneous with their abundance varying by several orders of magnitude. Although previous studies reported the profiles of the retinal cell types as the transcriptome level, there is no study regarding the open-chromatin profiles at a similar resolution. Here, we generated and integrated a multi-omics single-cell atlas of the adult human retina, including over 250K nuclei for single-nuclei RNA-seq and 137K nuclei for single-nuclei ATAC-seq. Through enrichment of rare cell types, this single cell multiome atlas is more comprehensive than previous human retina studies. Cross species comparison of the retina atlas among human, monkey, mice, and chicken revealed relatively conserved and non-conserved types. Interestingly, the overall cell heterogeneity in primate retina decreases compared to that of rodent and chicken retina. Furthermore, integrative analysis of the single cell multi-omics data identified 35k distal cis-element-gene pairs with most of these cis-elements being cell type specific. We also showed that the cis-element-gene relationship in different cell types within the same class could be highly heterogenous. Moreover, we constructed transcription factor (TF)-target regulons for over 200 TFs, partitioned the TFs into distinct co-active modules, and annotated each module based on their cell-type specificity. Taken together, we present the most comprehensive single-cell multi-omics atlas of the human retina as a valuable resource that enables systematic in-depth molecular characterization at individual cell type resolution.
Calredoxin regulates the chloroplast NADPH-dependent thioredoxin reductase inChlamydomonas reinhardtii
Authors: Zinzius Karen , Marchetti Giulia Maria , Fischer Ronja , Milrad Yuval , Oltmanns Anne , Kelterborn Simon , Yacoby Iftach , Hegemann Peter , Scholz Martin , Hippler Michael
Published: November 2022

Calredoxin (CRX) is a calcium (Ca2+)-dependent thioredoxin (TRX) in the chloroplast ofChlamydomonas reinhardtiiwith largely unclear physiological role. We elucidated the CRX functionality by performing in-depth quantitative proteomics of wild type cells in comparison withcrxinsertional mutant (IMcrx), two CRISPR/Cas9 KO mutants and CRX rescues. These analyses revealed that the chloroplast NADPH-dependent TRX reductase (NTRC) is co-regulated with CRX. Electron transfer measurements revealed that CRX inhibits NADPH-dependent reduction of oxidized chloroplast 2-Cys peroxiredoxin (PRX1) via NTRC and that the function of the NADPH-NTRC complex is under strict control of CRX. Via non-reducing SDS-PAGE assays and mass spectrometry, our data also demonstrated that PRX1 is more oxidized under high light (HL) conditions in the absence of CRX. The redox tuning of PRX1 and control of the NADPH-NTRC complex via CRX interconnects redox control with active photosynthetic electron transport and metabolism as well as Ca2+signaling. In this way, an economic use of NADPH for PRX1 reduction is ensured. The finding, that the absence of CRX under HL conditions severely inhibited light-driven CO2fixation underpins the importance of CRX for redox tuning as well as for efficient photosynthesis.

One-sentence summary

Calredoxin dependent redox regulation ensures efficient photosynthesis.
Metabolic consequences of polyphosphate synthesis and imminent phosphate limitation
Authors: Kim Geun-Don , Qiu Danye , Jessen Henning , Mayer Andreas
Published: November 2022

Cells stabilize intracellular inorganic phosphate (Pi) to compromise between large biosynthetic needs and detrimental bioenergetic effects of Pi. Pihomeostasis in eukaryotes employs SPXs domains, which are receptors for inositol pyrophosphates. We explored how polymerization and storage of Pi in acidocalcisome-like vacuoles supports S. cerevisiae metabolism and how these cells recognize Piscarcity. Whereas Pistarvation affects numerous metabolic pathways, beginning Piscarcity affects few metabolites. These include inositol pyrophosphates and ATP, a low-affinity substrate for inositol pyrophosphate-synthesizing kinases. Declining ATP and inositol pyrophosphates may thus be indicators of impending Pilimitation. Actual Pistarvation triggers accumulation of the purine synthesis intermediate 5- aminoimidazole-4-carboxamide ribonucleotide (AICAR), which activates Pi-dependent transcription factors. Cells lacking polyphosphate show Pistarvation features already under Pi-replete conditions, suggesting that vacuolar polyphosphate supplies Pifor metabolism even when Piis abundant. However, polyphosphate deficiency also generates unique metabolic changes that are not observed in starving wildtype cells. Polyphosphate in acidocalcisome-like vacuoles may hence be more than a global phosphate reserve and channel Pito preferred cellular processes.

Abstract importance

Cells must strike a delicate balance between the high demand of inorganic phosphate (Pi) for synthesizing nucleic acids and phospholipids, and its detrimental bioenergetic effects by reducing the free energy of nucleotide hydrolysis. The latter may stall metabolism. Therefore, microorganisms manage the import and export of phosphate, its conversion into osmotically inactive inorganic polyphosphates, and their storage in dedicated organelles, acidocalcisomes. Here, we provide novel insights into metabolic changes that cells may use to signal declining phosphate availability in the cytosol and differentiate it from actual phosphate starvation. We also analyze the role of acidocalcisome-like organelles in phosphate homeostasis. This uncovers an unexpected role of the polyphosphate pool in these organelles under phosphate-rich conditions, indicating that its metabolic roles go beyond that of a phosphate reserve for surviving starvation.
Quiet wakefulness: The influence of intraperitoneal and intranasal oxytocin on sleep-wake behaviour and neurophysiology in rats
Authors: Raymond Joel S , Everett Nicholas A , Gururajan Anand , Bowen Michael T
Published: November 2022

Introduction

Exogenous administration of the neuropeptide oxytocin exerts diverse effects on various neurobehavioural processes, including sleep and wakefulness. Since oxytocin can enhance attention to social and fear-related environmental cues, it should promote arousal and wakefulness. However, as oxytocin can attenuate stress, reduce activity, and elicit anxiolysis, oxytocin might also prime the brain for rest and promote sleep. At present, little research has comprehensively characterised the neuropsychopharmacology of oxytocin-induced effects on sleep-wake behaviour and no reconciliation of these two competing hypotheses has been proposed.

Methods

This study explored the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via intraperitoneal (i.p.; 0.1, 0.3 and 1 mg·kg-1) and intranasal (i.n.; 0.06, 1, 3 mg·kg-1) routes. Caffeine (i.p. and i.n.; 10 mg·kg-1) was administered as a wake-promoting positive control. To ascertain mechanism of action, pre-treatment experiments with the oxytocin receptor (OXTR) antagonist L-368,899 (i.p.; 5 mg·kg-1) followed by oxytocin (i.p.; 1 mg·kg-1) were also conducted.

Results

In both male and female rats, i.p. oxytocin promoted quiet wakefulness at the cost of suppressing active wakefulness, NREM and REM sleep. Several i.p. oxytocin-induced sleep-wake effects were mediated by OXTR binding. In contrast, i.n. oxytocin did not alter most sleep-wake outcomes at any dose tested. Both i.p. and i.n. caffeine demonstrated wake-promoting effects.

Conclusions

These findings help reconcile competing hypotheses of oxytocin-induced effects on sleep-wake behaviour: i.p. oxytocin promotes quiet wakefulness—a state of restful environmental awareness compatible with both oxytocin’s anxiolytic effects and its enhancement of processing complex stimuli.
Matrix prior for data transfer between single cell data types in latent Dirichlet allocation
Authors: Min Alan , Durham Timothy , Gevirtzman Louis , Noble William Stafford
Published: November 2022

Single cell ATAC-seq (scATAC-seq) enables the mapping of regulatory elements in fine-grained cell types. Despite this advance, analysis of the resulting data is challenging, and large scale scATAC-seq data are difficult to obtain and expensive to generate. This motivates a method to leverage information from previously generated large scale scATAC-seq or scRNA-seq data to guide our analysis of new scATAC-seq datasets. We analyze scATAC-seq data using latent Dirichlet allocation (LDA), a Bayesian algorithm that was developed to model text corpora, summarizing documents as mixtures of topics defined based on the words that distinguish the documents. When applied to scATAC-seq, LDA treats cells as documents and their accessible sites as words, identifying “topics” based on the cell type-specific accessible sites in those cells. Previous work used uniform symmetric priors in LDA, but we hypothesized that nonuniform matrix priors generated from LDA models trained on existing data sets may enable improved detection of cell types in new data sets, especially if they have relatively few cells. In this work, we test this hypothesis in scATAC-seq data from wholeC. elegansnematodes and SHARE-seq data from mouse skin cells. We show that nonsymmetric matrix priors for LDA improve our ability to capture cell type information from small scATAC-seq datasets.
Impairment of lipid homeostasis causes lysosomal accumulation of endogenous protein aggregates through ESCRT disruption
Authors: Yong John , Villalta Jacqueline E. , Vu Ngoc , Kukurugya Matthew A. , Olsson Niclas , López Magdalena Preciado , Lazzari-Dean Julia R. , Hake Kayley , McAllister Fiona , Bennett Bryson D. , Jan Calvin H.
Published: November 2022

Protein aggregation increases during aging and is a pathological hallmark of many age-related diseases. Protein homeostasis (proteostasis) depends on a core network of factors directly influencing protein production, folding, trafficking, and degradation. Cellular proteostasis also depends on the overall composition of the proteome and numerous environmental variables. Modulating this cellular proteostasis state can influence the stability of multiple endogenous proteins, yet the factors contributing to this state remain incompletely characterized. Here, we performed genome-wide CRISPRi screens to elucidate the modulators of proteostasis state in mammalian cells, using a fluorescent dye to monitor endogenous protein aggregation. These screens identified known components of the proteostasis network and uncovered a novel link between protein and lipid homeostasis. Increasing lipid uptake and/or disrupting lipid metabolism promotes the accumulation of sphingomyelins and cholesterol esters and drives the formation of detergent-insoluble protein aggregates at the lysosome. Proteome profiling of lysosomes revealed ESCRT accumulation, suggesting disruption of ESCRT disassembly, lysosomal membrane repair, and microautophagy. Lipid dysregulation leads to lysosomal membrane permeabilization but does not otherwise impact fundamental aspects of lysosomal and proteasomal functions. Together, these results demonstrate that lipid dysregulation disrupts ESCRT function and impairs proteostasis.
Accurate microRNA annotation of animal genomes using trained covariance models of curated microRNA complements in MirMachine
Authors: Umu Sinan Uğur , Paynter Vanessa M. , Trondsen Håvard , Buschmann Tilo , Rounge Trine B. , Peterson Kevin J. , Fromm Bastian
Published: November 2022

The annotation of microRNAs, an important class of post-transcriptional regulators, depends on the availability of transcriptomics data and expert knowledge. This led to a large gap between novel genomes made available and high-quality microRNA complements. Using >16,000 microRNAs from the manually curated microRNA gene database MirGeneDB, we generated trained covariance models for all conserved microRNA families. These models are available in MirMachine, our new tool for the annotation of conserved microRNA complements from genomes only. We successfully applied MirMachine to a wide range of animal species, including those with very large genomes, additional genome duplications and extinct species, where smallRNA sequencing will be hard to achieve. We further describe a microRNA score of expected microRNAs that can be used to assess the completeness of genome assemblies. MirMachine closes a long-persisting gap in the microRNA field facilitating automated genome annotation pipelines and deeper studies on the evolution of genome regulation, even in extinct organisms.

Highlights

An annotation pipeline using trained covariance models of microRNA families

Enables massive parallel annotation of microRNA complements of genomes

MirMachine creates meaningful annotations for very large and extinct genomes

microRNA score to assess genome assembly completeness

Graphical abstract
Direct observation of the evolution of cell-type specific microRNA expression signatures supports the hematopoietic origin model of endothelial cells
Authors: Jenike Ana E. , Jenike Katharine M. , Peterson Kevin J. , Fromm Bastian , Halushka Marc K.
Published: November 2022

The evolution of specialized cell-types is a long-standing interest of biologists, but given the deep time-scales very difficult to reconstruct or observe. microRNAs have been linked to the evolution of cellular complexity and may inform on specialization. The endothelium is a vertebrate specific specialization of the circulatory system that enabled a critical new level of vasoregulation. The evolutionary origin of these endothelial cells is unclear. We hypothesized that Mir-126, an endothelial cell-specific microRNA may be informative.

We here reconstruct the evolutionary history of Mir-126. Mir-126 likely appeared in the last common ancestor of vertebrates and tunicates, a species without an endothelium, within an intron of the evolutionary much older EGF Like Domain Multiple (Egfl) locus. Mir-126 has a complex evolutionary history due to duplications and losses of both the host gene and the microRNA. Taking advantage of the strong evolutionary conservation of the microRNA among Olfactores, and using RNA in situ hybridization (RISH), we localized Mir-126 in the tunicateCiona robusta. We found exclusive expression of the mature Mir-126 in granular amebocytes, supporting a long-proposed scenario that endothelial cells arose from hemoblasts, a type of proto-endothelial amoebocyte found throughout invertebrates.

This observed change of expression of Mir-126 from proto-endothelial amoebocytes in the tunicate to endothelial cells in vertebrates is the first direct observation of the evolution of a cell-type in relation to microRNA expression indicating that microRNAs can be a prerequisite of cell-type evolution.

Research Highlights

direct observation of cell-type evolution

high conservation of sequence enables for simple RISH experiment of expression

Mir-126 follows the evolution of hematopoetic cells to endothelial cells
The AUX1-AFB1-CNGC14 module establishes longitudinal root surface pH profile
Authors: Serre Nelson BC , Wernerová Daša , Vittal Pruthvi , Dubey Shiv Mani , Medvecká Eva , Jelínková Adriana , Petrášek Jan , Grossmann Guido , Fendrych Matyáš
Published: November 2022

Plant roots navigate in the soil environments following the gravity vector. Cell divisions in the meristem and rapid cell growth in the elongation zone propel the root tips through the soil. Actively elongating cells acidify their apoplast to enable cell wall extension by the activity of plasma membrane AHA H+-ATPases. The phytohormone auxin, central regulator of gravitropic response and root development, inhibits root cell growth, likely by rising the pH of the apoplast. However, the role of auxin in the regulation of the apoplastic pH gradient along the root tip is unclear. Here we show, by using an improved method for visualization and quantification of root surface pH, that theArabidopsis thalianaroot surface pH shows distinct acidic and alkaline zones, which are not primarily determined by the activity of AHA H+-ATPases. Instead, the distinct domain of alkaline pH in the root transition zone is controlled by a rapid auxin response module, consisting of the AUX1 auxin influx carrier, the AFB1 auxin co-receptor and the CNCG14 calcium channel. We demonstrate that the rapid auxin response pathway is required for an efficient navigation of the root tip.