bluuebunny/crossref_metadata_2025_split huggingface dataset:
WDR23 mediates NRF2 proteostasis and cytoprotective capacity in the hippocampus
Authors: Liu Jiahui , Duangjan Chatrawee , Irwin Ronald W. , Curran Sean P. 
Published: October 2023

ABSTRACTPathogenic brain aging and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are characterized by chronic neuroinflammation and the accumulation of dysfunctional or misfolded proteins that lead to progressive neuronal cell death. Here we demonstrate that a murine model with global loss of the CUL4-DDB1 substrate receptor WDR23 (Wdr23KO) results in changes in multiple age-related hippocampal-dependent behaviors. The behavioral differences observed inWdr23KOanimals accompany the stabilization of the NRF2/NFE2L2 protein, an increase in RNA transcripts regulated by this cytoprotective transcription factor, and an increase in the steady state level of antioxidant defense proteins. Taken together, these findings reveal a role for WDR23-proteostasis in mediating cytoprotective capacity in the hippocampus and reveal the potential for targeting WDR23-NRF2 signaling interactions for development of therapies for neurodegenerative disorders.HIGHLIGHTSWDR23 regulates NRF2/NFE2L2 stability in the mouse hippocampusLoss ofWdr23significantly increases the expression of NFE2L2/NRF2 target genesGlobal loss of WDR23 influences age-related behaviors differentially in males and females
Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from Two-sample Mendelian randomization
Authors: Habibi Danial , Teymoori Farshad , Ebrahimi Navid , Tehrani Fateh Sahand , Najd-Hassan-Bonab Leila , Saeidian Amir Hossein , Soleymani Taloubaghi Alireza , Asgarian Sara , Hosseinpanah Farhad , Hakonarson Hakon , Azizi Fereidoun , Hedayati Mehdi , Daneshpour Maryam Sadat , Akbarzadeh Mahdi , Mansourian Marjan 
Published: October 2023

AbstractBackground/AimThe putative association between serum 25 hydroxyvitamin D concentration 25(OH)D and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES.MethodThe summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls).ResultsOur results unveiled 99 SNPs contributing a causal relationship between 25(OH)D and CES using IVW [OR□=□0.82, 95% CI: 0.67-0.98, p□=□0.037]. Horizontal pleiotropy was not seen by the MR-Egger intercept-based test [MR-Egger intercept□=□0.001; p□=□0.792], suggesting an absence of horizontal pleiotropy. Cochrane’s Q value [Q=78.71, p-value□=□0.924], Rucker’s Q [Q=78.64, p-value=0.913], and I2=0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity in the connection between 25(OH)D and CES. This result remained consistent using different MR method and sensitivity analyses, including Maximum likelihood [OR=0.82, 95%CI: 0.67-0.98, p-value=0.036], Constrained maximum likelihood method [OR=0.76, 95%CI: 0.64-0.90, p-value=0.002], Debiased inverse-variance weighted method [OR=0.82, 95%CI: 0.68-0.99, p-value=0.002], MR-PRESSO [OR=0.82, 95%CI 0.77-0.87, p-value=0.022], RAPS [OR=0.82, 95%CI 0.67-0.98, p-value=0.038], MR-Lasso [OR=0.82, 95%CI 0.68-0.99, p-value=0.037].ConclusionOur MR analysis provides suggestive evidence that increased 25(OH)D levels may play a causally protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.
Transdiagnostic failure to adapt interoceptive precision estimates across affective, substance use, and eating disorders: A replication study
Authors: Lavalley Claire A. , Hakimi Navid , Taylor Samuel , Kuplicki Rayus , Forthman Katherine L. , Stewart Jennifer L. , Paulus Martin P. , Khalsa Sahib S. , Smith Ryan 
Published: October 2023

AbstractRecent computational theories of interoception suggest that perception of bodily states rests upon an expected reliability- or precision-weighted integration of afferent signals and prior beliefs. The computational psychiatry framework further suggests that aberrant precision-weighting may lead to misestimation of bodily states, potentially hindering effective visceral regulation and promoting psychopathology. In a previous study, we fit a Bayesian computational model of perception to behavior on a heartbeat tapping task to test whether aberrant precision-weighting was associated with misestimation of bodily states. We found that, during an interoceptive perturbation designed to amplify afferent signal precision (inspiratory breath-holding), healthy individuals increased the precision-weighting assigned to ascending cardiac signals (relative to resting conditions), while individuals with symptoms of anxiety, depression, substance use disorders, and/or eating disorders did not. A second study also replicated the pattern observed in healthy participants. In this pre-registered study, we aimed to replicate our prior findings in a new transdiagnostic patient sample (N=285) similar to the one in the original study. These new results successfully replicated those found in our previous study, indicating that, transdiagnostically, patients were unable to adjust beliefs about the reliability of interoceptive signals – preventing the ability to accurately perceive changes in their bodily state. Follow-up analyses combining samples from the previous and current study (N=719) also afforded the power to identify group differences within narrower diagnostic groups and to examine predictive accuracy when logistic regression models were trained on one sample and tested on the other. Given the increased confidence in the generalizability of these effects, future studies should examine the utility of interceptive precision measures in predicting treatment outcomes or identify whether these computational mechanisms might represent novel therapeutic targets for improving visceral regulation.
Daughter circumcision and maternal life satisfaction: A cultural moderation effect revealed across two studies
Authors: Strand Paul S. , Maxwell Providence , Trang Justin 
Published: October 2023

ABSTRACTIntroductionThe present paper explored the relationship between maternal life satisfaction and the intergenerational transmission of female genital cutting (FGC; female circumcision).MethodsAcross two studies with more than 85,000 participants in 15 countries, maternal surveys reveal that the association is positive and moderated by country-level FGC prevalence.ResultsContrary to predictions, in countries in which FGC is uncommon, it is more positively associated with maternal life satisfaction; and in countries in which it is common, it is weakly or negatively associated with maternal life satisfaction.ConclusionResults suggest a diversity of social motives for FGM. Customized messaging to reduce its inter-generational transmission should be considered.KEY MESSAGESWhat is already known about this topic?Female genital cutting (FGC) has negative implications for health and gender equality and is practiced to different degrees in countries in parts of Africa, Asia, the Middle East, and their diasporas.What this study adds?This study explored the intergenerational transmission of FGC—in particular, how daughter FGC relates to maternal life satisfaction. Contrary to expectations, life satisfaction ratings were higher for mothers of circumcised daughters, although this relationship was moderated by country-level FGC frequency. In countries in which it is more common, daughter FGC is less strongly or negatively associated with maternal life satisfaction.How might this study affect research, practice, or policy?Study findings may inform anti-FGC messaging. In countries in which FGC is common, messaging should highlight its association with relative maternal dissatisfaction. In countries in which it is uncommon, messaging should highlight alternatives to FGC as an expression of cultural identity.
Single-value fMRI scores reflect both stage and risk across the Alzheimer’s disease continuum
Authors: Soch Joram , Richter Anni , Kizilirmak Jasmin M. , Schütze Hartmut , Ziegler Gabriel , Altenstein Slawek , Brosseron Frederic , Dechent Peter , Fliessbach Klaus , Freiesleben Silka Dawn , Glanz Wenzel , Gref Daria , Heneka Michael T. , Hetzer Stefan , Incesoy Enise I. , Kilimann Ingo , Kimmich Okka , Kleineidam Luca , Kuhn Elizabeth , Laske Christoph , Lohse Andrea , Lüsebrink Falk , Munk Matthias H. , Peters Oliver , Preis Lukas , Priller Josef , Ramirez Alfredo , Roeske Sandra , Rostamzadeh Ayda , Roy-Kluth Nina , Scheffler Klaus , Schmid Matthias , Schneider Anja , Spottke Annika , Spruth Eike Jakob , Teipel Stefan , Wiltfang Jens , Jessen Frank , Wagner Michael , Düzel Emrah , Schott Björn H. 
Published: October 2023

AbstractSingle-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer’s disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD).To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants’ whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype.Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel.Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.
Time-Dependent ECG-AI Prediction of Fatal Coronary Heart Disease
Authors: Butler L. , Ivanov A. , Celik T. , Karabayir I. , Chinthala L. , Tootooni S. M. , Jaeger B. C , Doerr A. , McManus D. D. , Davis L. R. , Herrington D. , Akbilgic O. 
Published: October 2023

AbstractBackgroundSudden cardiac death (SCD) affects >4 million people globally, and ∽300,000 yearly in the US. Fatal coronary heart disease (FCHD) is used as a proxy to SCD when coronary disease is present and no other causes of death can be identified. Electrocardiographic (ECG) artificial intelligence (AI) models (ECG-AI) show promise in predicting adverse coronary events yet their application to FCHD is limited.ObjectivesThis research aimed to develop accurate ECG-AI models to predict risk for FCHD within the general population using waveform 12- and single-lead ECG data as well as assess time-dependent risk.MethodsStandard 10-second 12-lead ECGs sampled at 250Hz, demographic and clinical data from University of Tennessee Health Science Center (UTHSC) were used to develop and validate models. Eight models were developed and tested: two classification models with convolutional neural networks (CNN) using 12- and single-lead ECGs as inputs (12-ECG-AI and 1-ECG-AI, respectively) and six time- dependent cox proportional hazard regression (CPHR) models using demographics, clinical data and ECG-AI outputs. The dataset was split into 80% for model derivation, with five-fold cross-validation, and 20% holdout test set. Models were evaluated using the AUC and C-Index. Correlation of predicted risks from the 12-lead (12-ECG-AI) and single-lead (1-ECG-AI) CNN models was assessed.ResultsA total of 50,132 patients were included in this study (29,093 controls and 21,039 cases) with a total of 167,662 ECGs with mean age of 62.50±14.80years, 53.4% males and 48.5% African-Americans. The 12- and 1-ECG-AI models resulted AUCs=0.77 and 0.76, respectively on the holdout data. The best performing model was C12-ECG-AI-Cox (demographics+clinical+ECG) with no time restriction AUC=0.85(0.84-0.86) and C-Index= 0.78(0.77-0.79). 2-year FCHD risk prediction reached AUC=0.91(0.90-0.92). The 12-/1-ECG-AI models’ predictions were highly correlated (R2= 0.72).Conclusion2-year risk for FCHD can be predicted with moderate accuracy from ECG data alone. When combined with other data, a very high accuracy was obtained. High correlation between single-lead and 12-lead ECG models infer opportunities for screening larger patient populations for FCHD risk.Graphical Abstract
FSL-CP: A Benchmark for Small Molecule Activity Few-Shot Prediction using Cell Microscopy Images
Authors: Ha Son V. , Leuschner Lucas , Czodrowski Paul 
Published: October 2023

AbstractPredicting small molecule activities using information from high-throughput microscopy images has been shown to tremendously increase hit rates and chemical diversity of the hits in previous drug discovery projects. However, due to high cost of acquiring data or ethical reasons, data sparsity remains a big challenge in drug discovery. This opens up the opportunity for few-shot prediction: fine-tuning a model on a low-data assay of interest after pretraining on other more populated assays. Previous efforts have been made to establish a benchmark for few-shot learning of molecules based on molecular structure. With cell images as a molecular representation, methods in the computer vision domain are also applicable for activity prediction. In this paper, we make two contributions: a) A public data set for few-shot learning with cell microscopy images for the scientific community, b) A range of baseline models encompassing different existing single-task, multi-task and meta-learning approaches.
Compensation of compromised PRC2 regulation by a miRNA ensures robustness of Arabidopsis leaf development
Authors: Maugarny Aude , Vialette Aurélie , Adroher Bernard , Mathy-Franchet Nathalie , Roudier François , Laufs Patrick 
Published: October 2023

AbstractRobustness is pervasive throughout biological systems, enabling them to maintain persistent outputs despite perturbations in their components. Here, we reveal a novel mechanism contributing to leaf morphology robustness in the face of genetic perturbations. In Arabidopsis, leaf shape is established during early development through the quantitative action of theCUP-SHAPED COTYLEDON2(CUC2) gene that is negatively regulated by the co-expressedMICRORNA164A(MIR164A) gene. Compromised epigenetic regulation due to defective Polycomb Repressive Complex 2 (PRC2) function results in the transcriptional derepression ofCUC2but has no impact on CUC2 protein dynamics or early morphogenesis. We solve this apparent paradox by showing that compromised PRC2 function simultaneously activates a compensatory mechanism involving another member of theMIR164gene family, theMIR164Bgene. This mechanism dampens CUC2 protein levels, thereby compensating for compromised PRC2 function and canalizing early leaf morphogenesis. Furthermore, we show that this compensation mechanism is active under different environmental conditions. Our findings shed light on how the interplay between different types of transcriptional regulation can contribute to developmental robustness.
WITHDRAWN: Nitrogen sources enhance siderophore-mediated competition for iron between potato common scab and late blight causative agents
Authors: Stulanovic Nudzejma , Kerdel Yasmine , Rezende Lucas , Deflandre Benoit , Burguet Pierre , Belde Loic , Denoel Romane , Tellatin Deborah , Rigolet Augustin , Hanikenne Marc , Quinton Loic , Ongena Marc , Rigali Sebastien 
Published: October 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to the fact that theP.infestansstrain received from third parties is not the one referred in the manuscript despite having the certificate from the providing collection. All the experiments and data are correct but not included into a proper research context. A new version of this work will be published in near future. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Biodistribution Analysis of Peptide-Coated Magnetic Iron Nanoparticles: A Simple and Quantitative Method
Authors: Natarajan Pavithra , Horak Katherine , Rowe Jennifer , Lingo Joshua , Tomich John M , Fleming Sherry D 
Published: October 2023

ABSTRACTBiodistribution is the tracking of compounds or molecules of interest in the subject which is integral to understanding their anticipated efficacy and safety. Nanoparticles are highly desirable delivery systems which have the ability to deliver higher nucleic acid and drug payloads and they have enhanced tumor permeability due to their unique properties such as high surface area to volume ratio. Studying the biodistribution of nanoparticles is crucial to understand their effectiveness and safety in vivo, facilitate a more application driven approach for nanoparticle development which will lead to their successful translation into clinical use. In this study, we present a relatively simple method to determine the biodistribution of magnetic iron nanoparticles in mice. Branched Amphiphilic Peptide coated Magnetic Nanobeads BAPc-MNBs like their counterpart i.e., Branched Amphiphilic Peptide capsules (BAPCs) with a hollow water-filled core, are readily taken up by cells in vitro and have widespread application as a nanodelivery systems. We evaluated the BAPc-MNBs tissue distribution in wildtype mice injected intravenously (i.v.), intraperitoneally (i.p.) or orally gavaged to understand the biological interactions of the peptide nanoparticles and to further the development of branched amphiphilic peptides-based nanoparticles. BAPc-MNBs were distributed widely to various organs when injected i.v. and were eliminated from the system via the intestines in feces. The spleen was found to accumulate the highest amount of BAPc-MNBs in mice administered the NPs i.v. and i.p. while they were not absorbed into the system via oral gavage. This study not only presents a relatively simple quantification method to determine in vivo biodistribution of magnetic iron nanoparticles that can be widely applied but also demonstrates the potential of Branched Amphiphilic Peptides in the form of BAPCs or BAPc-MNBs as a delivery system.
DNA methylation is linked to the monoallelic expression ofMRP3, a diatom mating type determining gene
Authors: Ruggiero Antonella , Mager Svenja , Manfellotto Francesco , Tuccio Viviana Di , Nishimura Tomohiro , Pan Leslie , Russo Monia T. , Sanges Remo , Ferrante Maria I. 
Published: October 2023

AbstractDiatoms are unicellular microalgae widely distributed in aquatic ecosystems. In diatoms, sexual reproduction is needed to counteract cell miniaturization imposed by the rigid silica shell, and only small cells, below a species-specific size threshold, are competent for sex.We performed a genome-wide Enzymatic Methyl-seq analysis in the heterothallic diatomPseudo-nitzschia multistriatacomparing cells of different size and opposite mating type (MT) to investigate potential epigenetic controls in life cycle transitions. We found an imprinting-like pattern of methylation at the sex locus: alleles of the gene responsible for the specification of the MT+,MRP3, are hypermethylated in MT- and differentially methylated in MT+, with transcription occurring only on the MT+ hypomethylated variant. The methylation pattern is overall stable over theP. multistriatalife cycle. Absence of methylation inMRP3is necessary for its expression but not sufficient, since large non-sexual cells have the same methylation profile of small sexual cells but do not expressMRP3, suggesting that additional controls are involved in the mechanism of sex determination.The methylation profile of the mating type determining geneMRP3of the diatomPseudo-nitzschia multistriatais different between opposite mating types. Lack of methylation is necessary but not sufficient forMRP3expression in the sexually competent MT+ strains.Highlights- The mating type locus is differentially methylated in MT+ and MT-- DNA methylation is linked to MRP3 expression- DNA methylation does not play a role in the acquisition of sexual competence
Microbiota may affect the tumor type but not overall tumor development in two models of heritable cancer
Authors: Spring Jessica , Gurbuxani Sandeep , Golovkina Tatyana 
Published: October 2023

AbstractMicrobial impact on tumorigenesis of heritable cancers proximal to the gut is well documented. Whether the microbiota influences cancers arising from inborn mutations at sites distal to the gut is undetermined. Using two models of heritable cancer, we found the microbiota to be inconsequential for tumor development. However, the type of tumor that develops may be influenced by the microbiota. This work furthers our understanding of the microbial impact on tumor development.