bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractThe 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

Abstract
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

Abstract

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

Abstract

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 &lt;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

AbstractBackground and HypothesisFamilial 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 DesignNeurocognition 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 ResultsSet-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.ConclusionsEarly 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

AbstractThis 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.
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

AbstractCell 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

AbstractCalredoxin (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 summaryCalredoxin 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

AbstractCells 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 importanceCells 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

AbstractIntroductionExogenous 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.MethodsThis 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.ResultsIn 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.ConclusionsThese 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

AbstractSingle 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

AbstractProtein 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.