bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative Distribution of DnaA and DNA inEscherichia coliCells as a Factor of Their Phenotypic Variability
Authors: Namboodiri Sharanya K. , Aranovich Alexander , Hadad Uzi , Gheber Levi A. , Feingold Mario , Fishov Itzhak
Published: August 2024

Phenotypic variability in isogenic bacterial populations is a remarkable feature that helps them cope with external stresses, yet it is incompletely understood. This variability can stem from gene expression noise and/or unequal partitioning of low-copy-number freely diffusing proteins during cell division. Some high-copy-number components are transiently associated with almost immobile large assemblies (hyperstructures) and may be unequally distributed, contributing to bacterial phenotypic variability. We focus on the nucleoid hyperstructure containing numerous DNA-associated proteins, including the replication initiator DnaA. Previously we found an increasing asynchrony in the nucleoid segregation dynamics in growingE. colicell lineages and suggested that variable replication initiation timing may be the main cause of this phenomenon. Here we support this hypothesis revealing that DnaA/DNA variability represents a key factor leading to the enhanced asynchrony inE. coli. We followed the intra- and intercellular distribution of fluorescently tagged DnaA and histone-like HU chromosomally encoded under their native promoters. The diffusion rate of DnaA is low, corresponding to a diffusion-binding mode of mobility, but still one order faster than that of HU. The intracellular distribution of DnaA concentration is homogeneous in contrast to the significant asymmetry in the distribution of HU to the cell halves, leading to unequal DNA content of nucleoids and DnaA/DNA ratios in future daughter compartments. Accordingly, the intercellular variabilities of HU concentration (CV=26%) and DnaA/DNA ratio (CV=18%) are high. The variable DnaA/DNA may cause a variable replication initiation time (initiation noise). Asynchronous initiation at different replication origins may, in turn, be the mechanism leading to the observed asymmetric intracellular DNA distribution. Our findings indicate that the feature determining the variability of initiation time inE. coliis the DnaA/DNA ratio rather than separately each of them. We provide a likely mechanism for the ‘loss of segregation synchrony’ phenomenon.
From insect endosymbiont to phloem colonizer: comparative genomics unveils the lifestyle transition of phytopathogenicArsenophonusstrains
Authors: Mahillon Mathieu , Debonneville Christophe , Groux Raphaël , Roquis David , Brodard Justine , Faoro Franco , Foissac Xavier , Schumpp Olivier , Dittmer Jessica
Published: August 2024

Bacteria infecting the plant phloem represent a growing threat worldwide. While these organisms often resist in vitro culture, they multiply both in plant sieve elements and hemipteran vectors. Such cross-kingdom parasitic lifestyle has emerged in diverse taxa via distinct ecological routes. In the genusArsenophonus, the phloem pathogens 'Candidatus Arsenophonus phytopathogenicus' (Ap) and 'Ca. Phlomobacter fragariae' (Pf) have evolved from insect endosymbionts, but the genetic mechanisms underlying this transition have not been explored. To fill this gap, we obtained the genomes of both strains from insect host metagenomes. The resulting assemblies are highly similar in size and functional repertoire, rich in viral sequences, and closely resemble the genomes of several facultative endosymbioticArsenophonusstrains of sap-sucking hemipterans. However, a phylogenomic analysis demonstrated distinct origins, as Ap belongs to the 'Triatominarum' clade whereas Pf represents a distant species. We identified a set of orthologs encoded only by Ap and Pf in the genus, including hydrolytic enzymes likely targeting plant substrates. In particular, both bacteria encode plant cell-wall degrading enzymes and cysteine peptidases related to xylellain, a papain-like peptidase fromXylella fastidiosa, for which close homologs are found in diverse proteobacteria infecting the plant vasculature. In silico predictions and expression analyses further support a role during phloem colonization for several of the shared orthologs. We conclude that the double emergence of phytopathogenicity inArsenophonusmay have been mediated by a few horizontal gene transfer events, involving genes first acquired from other proteobacteria including phytopathogens.
Antiviral Mx proteins have an ancient origin and widespread distribution among eukaryotes
Authors: Langley Caroline A. , Dietzen Peter A. , Emerman Michael , Tenthorey Jeannette L. , Malik Harmit S.
Published: August 2024

First identified in mammals, Mx proteins are potent antivirals against a broad swathe of viruses. Mx proteins arose within the Dynamin superfamily of proteins (DSP), mediating critical cellular processes, such as endocytosis and mitochondrial, plastid, and peroxisomal dynamics. And yet, the evolutionary origins of Mx proteins are poorly understood. Using a series of phylogenomic analyses with stepwise increments in taxonomic coverage, we show that Mx proteins predate the interferon signaling system in vertebrates. Our analyses find an ancient monophyletic DSP lineage in eukaryotes that groups vertebrate and invertebrate Mx proteins with previously undescribed fungal MxF proteins, the relatively uncharacterized plant and algal Dynamin 4A/4C proteins, and representatives from several early-branching eukaryotic lineages. Thus, Mx-like proteins date back close to the origin of Eukarya. Our phylogenetic analyses also reveal that host-encoded and NCLDV (nucleocytoplasmic large DNA viruses)-encoded DSPs are interspersed in four distinct DSP lineages, indicating recurrent viral theft of host DSPs. Our analyses thus reveal an ancient history of viral and antiviral functions encoded by the Dynamin superfamily in eukaryotes.
A Strain ofStreptococcus mitisInhibits Biofilm Formation of Caries Pathogens via Abundant Hydrogen Peroxide Production
Authors: Williams Isabella , Tuckerman Jacob S. , Peters Daniel I. , Bangs Madisen , Williams Emily , Shin Iris J. , Kaspar Justin R.
Published: August 2024

Commensal oral streptococci that colonize supragingival biofilms deploy mechanisms to combat competitors within their niche. Here, we determined thatStreptococcus mitismore effectively inhibited biofilm formation ofStreptococcus mutanswithin a seven species panel. This phenotype was common amongst all assayed isolates ofS. mutans, but was specific to a single strain ofS. mitis, ATCC 49456. The growth inhibitory factor was not effectively carried in spent supernatants ofS. mitis. However, we documented ATCC 49456 to accumulate 4-5 times more hydrogen peroxide (H2O2) than other species tested, and 5-18 times more than otherS. mitisstrains assayed. TheS. mutansbiofilm formation inhibitory phenotype was reduced when grown in media containing catalase or with aS. mitismutant of pyruvate oxidase (spxB;pox), confirming that SpxB-dependent H2O2production was the main antagonistic factor. Addition ofS. mitiswithin hours afterS. mutansinoculation was effective at reducing biofilm biomass, but not for 24 h pre-formed biofilms. Transcriptome analysis revealed responses for bothS. mitisandS. mutans, with severalS. mutansdifferentially expressed genes following a gene expression pattern previously described, while others being unique to the interaction withS. mitis. Finally, we show thatS. mitisalso affected coculture biofilm formation of several other commensal streptococci. Our study shows that strains with abundant H2O2production are effective at inhibiting initial growth of caries pathogens likeS. mutans, but are less effective at disrupting pre-formed biofilms and have the potential to influence the stability of other oral commensal strains.
WITHDRAWN: Interspecies recombination between cassava brown streak disease-causing viruses
Authors: Astacio-Berrios Keryan , Duffy Siobain
Published: August 2024

Withdrawal Statement

The authors have withdrawn this manuscript because the putative interspecific recombinant sequences (MW961179.1, MW961204.1, MW961211.1 and MW961191.1), upon further scrutiny by the researchers who generated the data, have been revealed to be artifacts of assembly from illumina sequencing of plants with mixed CBSV/UCBSV infection. 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.
Allele ages provide limited information about the strength of negative selection
Authors: Shastry Vivaswat , Berg Jeremy J.
Published: August 2024

For many problems in population genetics, it is useful to characterize the distribution of fitness effects (DFE) ofde novomutations among a certain class of sites. A DFE is typically estimated by fitting an observed site frequency spectrum (SFS) to an expected SFS given a hypothesized distribution of selection coefficients and demographic history. The development of tools to infer gene trees from haplotype alignments, along with ancient DNA resources, provides us with additional information about the frequency trajectories of segregating mutations. Here, we ask how useful this additional information is for learning about the DFE, using the joint distribution on allele frequency and age to summarize information about the trajectory. To this end, we introduce an accurate and efficient numerical method for computing the density on the age of a segregating variant found at a given sample frequency, given the strength of selection and an arbitrarily complex population size history. We then use this framework to show that the unconditional age distribution of negatively selected alleles is very closely approximated by re-weighting the neutral age distribution in terms of the negatively selected SFS, suggesting that allele ages provide very little information about the DFE beyond that already contained in the present day frequency. To confirm this prediction, we extended the standard Poisson Random Field (PRF) method to incorporate the joint distribution of frequency and age in estimating selection coefficients, and test its performance using simulations. We find that when the full SFS is observed and the true allele ages are known, including ages in the estimation provides only small increases in the accuracy of estimated selection coefficients. However, if only sites with frequencies above a certain threshold are observed, then the true ages can provide substantial information about the selection coefficients, especially when the selection coefficient is large. When ages are estimated from haplotype data using state-of-the-art tools, uncertainty about the age abrogates most of the additional information in the fully observed SFS case, while the neutral prior assumed in these tools when estimating ages induces a downward bias in the case of the thresholded SFS.
PTEN neddylation aggravates CDK4/6 inhibitor resistance in breast cancer
Authors: Liu Fan , Liu Weixiao , Tan Yawen , Shang Yaxin , Ling Sihui , Jiang Xiaokun , Zhang Zhen , Sun Shiyao , Xie Ping
Published: August 2024

Background

The gradual emergence of a novel therapeutic approach lies in the restoration of tumor suppressive machinery. PTEN is a crucial negative regulator of the PI3K/Akt signaling pathway. Protein neddylation modification contributes to PTEN inactivation and fuels breast cancer progression.

Methods

In this study, well-established CDK4/6 inhibitor resistance models were used to detect the levels of PTEN neddylation. Co-immunoprecipitation,in vivoandin vitromodification assays and transcriptome data were integrated to delve into the mechanism. Following this, a PTEN CDK4/6 inhibitors in bothin situtumor models and breast cancer cells. Furthermore, in patient-derived organoids (PDOs), we combined the PTEN neddylation inhibitor with CDK4/6 inhibitors to confirm their inhibitory effect on breast cancer progression.

Results

We highlight that an elevated level of PTEN neddylation is markedly associated with resistance to palbociclib, a CDK4/6 inhibitor used in luminal subtype breast cancer patients. Mechanistically, PTEN neddylation activates the PI3K/Akt signaling pathway, and more notably, upregulates the activity of the AP-1 transcription factor. Our data showed that PTEN neddylation stabilizes JUND, a transcription factor involved in the AP-1, by disrupting its interaction with the E3 ubiquitin ligase ITCH. Consequently, activated JUND leads to the release of cytokines and chemokines, such as G-CSF, GM-CSF, IL-1RA, IL-1β, which in turn may drive an inflammatory tumor microenvironment, potentially contributing to drug resistance. Then, we identified Echinacoside as a potent inhibitor of PTEN neddylation bothin vivoandin vitroby disrupting its interaction with XIAP, the E3 ligase responsible for PTEN neddylation. Combination of Echinacoside could effectively overcome resistance to palbociclib in breast cancer treatment.

Conclusions

This novel insight underscores the potential of targeting PTEN neddylation as a promising strategy for restoring the activity of key tumor suppressor and overcoming resistance in breast cancer therapy.
Extensive Surveillance of Mosquitoes and molecular investigation of Arboviruses in central Iran; First Record of Molecular Identification ofCulex tarsalisin Qom Province
Authors: Abedi-Astaneh Fatemeh , Rad Hedaiatollah Raoofi , Pouriayevali Mohammad Hassan , Jalali Tahmineh , Izanlou Hassan , Hosseinalipour Seied Abbas , Hamta Amir , Es’haghieh Mohammad , Ebrahimi Mahdi , Ansari-Cheshmeh Mohammad Ali , Salehi-Vaziri Mostafa , Talbalaghi Asghar , Abbasi Ebrahim
Published: August 2024

Background

Arboviruses are one of the greatest threats to animal and public health.Culicidaefamily is one of the most important vectors for the transmission of Arboviruses in the world. According to the geographical, demographic and climatic features of Qom city in Iran, it can be a suitable region for vectors and therefore transmission of Arboviruses.

Methods

In this study, which was conducted between 2019 and 2020 in different parts of Qom city, 83,414 mosquitoes were collected and after evaluating the species of mosquitoes based on morphological and molecular detection, the presence of alphaviruses, flaviviruses and phleboviruses were evaluated using genus specific RT-PCR assays.

Results

In this study,Culex tarsalis, Culex theilerivoucher, Culex quinquefasciatusand most importantly for the first time in IranCulex tarsaliswere detected. No alphavirus, flavivirus and phlebovirus infection was identified in collected mosquitoes.

Conclusion

Climatic and weather changes are the basis for the growth and spread of vectors and consequently the spread of arboviral diseases, and this issue seems to be very important on the necessity of increasing and continuing entomological and virological studies.

Author Summary

Arboviruses pose significant threats to animal and public health globally, with mosquitoes from the Culicidae family serving as key vectors in their transmission. This study focuses on Qom city, Iran, which, due to its unique geographical, demographic, and climatic characteristics, provides a potentially suitable environment for these vectors. Over the course of 2019 to 2020, researchers collected 83,414 mosquitoes across various locations within Qom. Through morphological and molecular analysis, they identified species such asCulex tarsalis, Culex theileri, andCulex quinquefasciatus, notably reportingCulex tarsalisin Iran for the first time. Using genus-specific RT-PCR assays, the study evaluated the presence ofalphaviruses, flaviviruses, andphlebovirusesin the collected samples but found no evidence of infection. These findings underscore the importance of ongoing entomological and virological research, particularly given the potential for climatic changes to influence vector growth and the spread of arboviral diseases.
Predicting onward care needs at admission to reduce discharge delay using machine learning
Authors: Duckworth Chris , Burns Dan , Lamas Fernandez Carlos , Wright Mark , Leyland Rachael , Stammers Matthew , George Michael , Boniface Michael
Published: August 2024

Early identification of patients who require onward referral for social care can prevent delays to discharge from hospital. We introduce a machine learning (ML) model to identify potential social care needs at the first point of admission. The model performance is comparable to clinician’s predictions of discharge care needs, despite working with only a subset of the information available to the clinician. We find that ML and clinician perform better for identifying different types of care needs, highlighting the added value of a potential system supporting decision making. We also demonstrate the ability for ML to provide automated initial discharge need assessments, in the instance where initial clinical assessment is delayed. Finally, we demonstrate that combining clinician and machine predictions, in a hybrid model, provides even more accurate early predictions of onward social care requirements and demonstrates the potential for human-in-the-loop decision support systems in clinical practice.
From Goals to Gains: Results Based Management Revolutionizes NCD Care in Rural Egypt
Authors: Utterman Sonia , Hussein Muhammad , ElKady Mona , Awad Walaa , Marrison Amanda
Published: August 2024

This paper examines the application of Results Based Management (RBM) in a health program aimed at combating noncommunicable diseases (NCDs) in rural Egypt. The study focuses on a three-year initiative implemented from 2019 to 2022 across five governorates, targeting diabetes, hypertension, and cardiovascular diseases. Using a mixed-methods approach, we analyze the program’s design, implementation, and outcomes through the lens of RBM principles.

Our findings indicate that the adoption of RBM led to improved goal clarity, enhanced monitoring and evaluation processes, and increased accountability among stakeholders. The program achieved a 15% reduction in NCD-related mortality and a 22% increase in early detection rates. However, challenges were encountered in data collection and local capacity building.

This case study contributes to the growing body of literature on RBM in public health contexts, particularly in resource-limited settings. We conclude by offering recommendations for policymakers and program managers on effectively integrating RBM into health initiatives targeting NCDs in similar environments.
Retinograd-AI: An Open-source Automated Fundus Autofluorescence Retinal Image Gradability Assessment for Inherited Retinal Dystrophies
Authors: Naik Gunjan , Al-Khuzaei Saoud , Moghul Ismail , de Guimaraes Thales A. C. , Sen Sagnik , Daich Varela Malena , Liu Yichen , Bagga Pallavi , Fu Dun Jack , Moosajee Mariya , Madhusudhan Savita , Webster Andrew , De Silva Samantha , Patel Praveen J. , Mahroo Omar , Downes Susan M , Michaelides Michel , Balaskas Konstantinos , Pontikos Nikolas , Woof William
Published: August 2024

Purpose

To develop an automated system for assessing the quality of Fundus Autofluorescence (FAF) images in patients with inherited retinal diseases (IRD).

Methods

We annotated a dataset of 2445 FAF images from patients with Inherited Retinal Dystrophies which were assessed by three different expert graders. Graders marked images as either gradable (acceptable quality) or ungradable (poor quality), following a strict grading protocol. This dataset was used to train a Convolutional Neural Network (CNN) classification model to predict the gradability label of FAF images.

Results

Retinograd-AI achieves a performance of 91% accuracy on our held-out dataset of 133 images with an Area Under the Receiver Operator Characteristic (AUROC) of 0.94, indicating high performance in distinguishing between gradable and ungradable images. Applying Retinograd-AI to our full internal dataset, the highest proportion of gradable images was found in the 30-50 years age group, where 84.3% of images were rated as gradable, while the lowest was in 0-15 year olds, where only 45.2% of images were rated as gradable. 83.4% of images from male patients were rated as gradable, and 90.6% of images from female patients. By genotype, from the 30 most common genetic diagnoses, the highest proportion of gradable images was in patients with disease causing variants inPRPH2(93.9%), while the lowest wasRDH12(28.6%). Eye2Gene single-image gene classification top-5 accuracy on images rated by Retinograd-AI was 69.2%, while top-5 accuracy on images rated as ungradable was 39.0%. Retinograd-AI is open-sourced, and the source code and network weights are available under an MIT licence on GitHub athttps://github.com/Eye2Gene/retinograd-ai

Conclusions

Retinograd-AI is the first open-source AI model for automated retinal image quality assessment of FAF images in IRDs. Automated gradability assessment through Retinograd AI enables large scale analysis of retinal images, which is an essential part of developing good analysis pipelines, and real-time quality assessment, which is essential for deployment of AI algorithms, such as Eye2Gene, into clinical settings. Due to the diverse nature of IRD pathologies, Retinograd-AI may also be applicable to FAF imaging for other conditions, either in its current form or through transfer learning and fine-tuning.
Mass spectrometric profiling of estrogen and estrogen metabolites in human stool and plasma partially elucidates the role of the gut microbiome in estrogen recycling
Authors: Li Vince W. , Dong Tien S. , Funes Diana , Hernandez Laura , Reddy Srinivasa T. , Mayer Emeran , Chang Lin , Meriwether David
Published: August 2024

Estrogen and estrogen metabolites are commonly measured in human plasma and serum, but there exist almost no reports of estrogen measured in human stool. This methodological limitation in turn limits our understanding of the relationship between systemic and intestinal estrogen. We thus developed a highly sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for measuring free and conjugated forms of 15 estrogens and estrogen metabolites in human stool and plasma. We first investigated human stool and plasma estrogen in healthy control males; follicular and luteal phase premenopausal females; and postmenopausal females. Most estrogens were present in the plasma and stool of all groups, and plasma estrogen levels correlated with stool estrogen levels. In stool, estrogens were higher in premenopausal females, with estrogen levels rising across the menstrual cycle. We further combined these measures with shotgun metagenomic sequencing of the stool microbiomes. The level of estrogen deconjugation enzyme gene copy number (beta-glucuronidase + arylsulfatase) was higher in premenopausal females; while the gene copy numbers of beta-glucuronidase + arylsulfatase, but not beta-glucuronidase alone, correlated with reactivated stool estrogen in all groups. Moreover, deconjugation enzyme gene copy number correlated with plasma total estrogen in males and with individual plasma estrogen metabolites in all groups. These results support the hypothesis that gut microbial beta-glucuronidase and arylsulfatase control the reactivation of gut estrogen while modulating systemic levels through the uptake and recirculation of reactivated estrogen.
Biased recruitment of H3.3 by HIRA is dictated by de-/acetylation and determines transcription memory and response
Authors: Usha Satheesan Sandra , Chakrabarti Sourankur , Fulzele Amit , Marcellin Marlène , Locard-Paulet Marie , Peredo Anne Gonzalez-de , Kolthur-Seetharam Ullas
Published: August 2024

Chromatin plasticity and epigenetic memory, fundamental for eukaryotic biology, are determined by differential/regulatedde novodeposition or recycling of pre-existing histones, which in turn dictate transcriptional programs. Recruitment of the histone-H3 variant, H3.3, mediated by the HIRA chaperone complex, is both causally and consequentially associated with transcription. Despite decades of work, endogenous regulatory mechanisms that differentiate betweende novodeposition and recycling activities of HIRA are still unknown. Here, we have investigated the pivotal role of HIRA de-/acetylation in regulating its function. Our results unequivocally establish function separation effects of acetyl and deacetyl mimic mutations of lysine-600, vis-à-visde novodeposition or recycling of H3.3, respectively. Importantly, we demonstrate that HIRA deacetylation-dependent biased H3.3 recycling determines transcriptional output, possibly through preferential enrichment of H3.3-K36me3. Besides unraveling tunable regulatory mechanism that governs HIRA function, we illustrate a causal link between the chaperone activity, biased recruitment of pre-existing histones, and gene expression.
AnIn-VitroStandardized Protocol for Preparing Smoke Extract Media from Cigarette, Electronic Cigarette and Waterpipe
Authors: Al-Hashimi Amel , Shah Jagrut , Carpenter Roger , Morgan Winston , Meah Mohammed , Ruchaya Prashant J.
Published: August 2024

Cigarette smoke exposure is a major risk factor for various diseases, and in vitro studies using smoke medium (SM) are crucial for elucidating underlying mechanisms. However, the lack of standardized protocols for SM preparation has led to inconsistencies in experimental results. This paper presents an optimized protocol for reproducible generation of SM from conventional cigarette smoke extract (CSE), electronic cigarette smoke (ECS), and waterpipe vapour (WPV). The protocol involves:

A custom-built apparatus for smoke capture in a cell culture medium

Specific parameters mimicking human smoking topography

Rigorous aseptic techniques and safety measures

Extensive details are provided for material preparation, apparatus setup, smoke generation procedures, and post-processing steps. This standardized method enables reliable in vitro exposure models, easing comparative studies across different tobacco products. To prove protocol consistency, we present optical. Additionally, we highlight the protocol’s utility by figuring out the SM quality through analysing O.D. data and morphological changes, cell viability assays, ELISA and gene expression analyses i.e., RNA sequencing through severalin-vitromodels, i.e., Human Umbilical Vein Endothelial Cells, (HUVECs,Merck), human leukaemia monocytic cell line (THP-1, Sigma) and induced pluripotent stem cells differentiated to cardiomyocytes(iPSC-CMs,Axol)respectively. This optimized protocol addresses variability in SM preparation, enabling consistent investigations into smoke-induced pathologies and potential therapeutic interventions.

Graphical abstract

Specifications table
DROSHA, DICER and Damage-Induced long ncRNA control BMI1-dependent transcriptional repression at DNA double-strand break
Authors: Esposito Francesca , Capozzo Ilaria , Modafferi Stefania , Gioia Ubaldo , Manfredi Letizia , Iannelli Fabio , Colantoni Alessio , Riccardi Adelaide , di Lillo Alessia , Tavella Sara , Cabrini Matteo , d’Adda di Fagagna Fabrizio , Francia Sofia
Published: August 2024

Genome integrity is safeguarded by the DNA damage response (DDR). Controlled transcriptional dampening of genes surrounding DNA double-strand breaks (DSBs) has been shown to facilitate DNA repair. This phenomenon, defined as DSB-induced silencing incis(DISC), involves the DDR apical kinase ATM and the Polycomb Repressive Complex 1 (PRC1). Conversely, DSBs have also been reported to inducede novotranscription of damaged-induced long non-coding RNAs (dilncRNAs) in a MRE11-RAD50-NBS1 (MNR) complex-dependent manner. MRN also controls the recruitment to DSB of the ribonuclease DROSHA, which together with DICER, stimulates DDR signaling and DNA repair. Here, we reconcile these apparently contrasting observations by showing that dilncRNA, together with DROSHA and DICER, but not GW182-like proteins required for miRNA-mediated gene silencing, controls DISC. Indeed, similarly to ATM, MRN inhibition abolishes DISC while pharmacological enhancement of DICER ribonuclease activity by Enoxacin improves DISC. Importantly, Enoxacin administration restores DISC upon ATM inhibition, demonstrating that DICER promotes DISC independently from ATM. Differently, Enoxacin does not restore DISC upon MRN inhibition, suggesting that DICER acts downstream to dilncRNA biogenesis and DROSHA recruitment. Mechanistically, we show that DROSHA and DICER control the recruitment of the PRC1 component BMI1 at DSBs and the consequent H2A-K119 ubiquitination. Upon DSBs formation, BMI1 and DROSHA interact in an RNA-dependent manner. Indeed, BMI1 associates to dilncRNA and do so in a DROSHA- and DICER-dependent manner. Importantly, inhibition of dilncRNA function by antisense oligonucleotides or Cas13-mediated targeting is sufficient to reduce BMI1 recruitment and DISC at individual loci. We propose that dilncRNAs together with DROSHA and DICER control DISC at genomic DSB by supporting PRC1 recruitment and chromatin ubiquitination.
A modified decision tree improves generalization across multiple brains proteomic data sets and reveals the role of ferroptosis in Alzheimer’s disease
Authors: Ivanov Mark V. , Kopeykina Anna S. , Kazakova Elizaveta M. , Tarasova Irina A. , Sun Zhao , Postoenko Valeriy I. , Yang Jinghua , Gorshkov Mikhail V.
Published: August 2024

Low generalization to the patient cohort and variety of experimental conditions in the proteomic search for disease biomarkers are among the main reasons for the bumpy road of quantitative proteomics from discovery stage to clinical validation. Only a small fraction of biomarkers discovered so far by proteomic analysis reaches clinical trials. Here, we presented a machine learning-based workflow for proteomics data analysis, which partially solves some of these issues. In particular, we used a customized decision tree model, which was regulated using a newly introduced parameter, min_cohorts_leaf, that resulted in better generalization of trained models. Further, we analyzed the trend of feature importance’s curve as a function of min_cohorts_leaf parameter and found that it could be used for accurate feature selection to obtain a list of proteins with significantly improved generalization. Finally, we demonstrated that the recently introduced DirectMS1 search algorithm for protein identification and quantitation provides a simple, yet, a highly efficient solution for the problem of combining multiple data sets obtained using different experimental settings. The developed workflow was tested using five published LC-MS/MS data sets obtained in the large consortia studies of Alzheimer’s disease brain samples. The selected data sets consist of 535 files in total analyzed using label-free single-shot data-dependent or data-independent acquisitions. Using the proposed modified ExtraTrees model we found that the expressions of two proteins involved in ferroptosis Serotransferrin TRFE and DNA repair nuclease/redox regulator APEX1, are important for explaining a lack of dementia for patients with the presence of neuritic plaques and neurofibrillary tangles.
A developmental mechanism to regulate alternative polyadenylation in an adult stem cell lineage
Authors: Gallicchio Lorenzo , Matias Neuza R. , Morales-Polanco Fábian , Nava Iliana , Stern Sarah , Zeng Yi , Fuller Margaret T.
Published: August 2024

Alternative cleavage and polyadenylation (APA) often results in production of mRNA isoforms with either longer or shorter 3′ UTRs from the same genetic locus, potentially impacting mRNA translation, localization, and stability. Developmentally regulated APA can thus make major contributions to cell type-specific gene expression programs as cells differentiate. DuringDrosophilaspermatogenesis, ∼500 genes undergo APA when proliferating spermatogonia differentiate into spermatocytes, producing transcripts with shortened 3′ UTRs, leading to profound stage-specific changes in the proteins expressed. The molecular mechanisms that specify usage of upstream polyadenylation sites in spermatocytes are thus key to understanding the changes in cell state. Here, we show that upregulation of PCF11 and Cbc, the two components of cleavage factor II (CFII), orchestrates APA duringDrosophilaspermatogenesis. Knockdown ofPCF11orcbcin spermatocytes caused dysregulation of APA, with many transcripts normally cleaved at a proximal site in spermatocytes now cleaved at their distal site, as in spermatogonia. Forced overexpression of CFII components in spermatogonia switched cleavage of some transcripts to the proximal site normally used in spermatocytes. Our findings reveal a developmental mechanism where changes in expression of specific cleavage factors can direct cell type-specific APA at selected genes.
What goes up must come down: off switches for regulatory RNAs
Authors: McJunkin Katherine , Gottesman Susan
Published: August 2024

Small RNAs base pair with and regulate mRNA translation and stability. For both bacterial small regulatory RNAs and eukaryotic microRNAs, association with partner proteins is critical for the stability and function of the regulatory RNAs. We review the mechanisms for degradation of these RNAs: displacement of the regulatory RNA from its protein partner (in bacteria) or destruction of the protein and its associated microRNAs (in eukaryotes). These mechanisms can allow specific destruction of a regulatory RNA via pairing with a decay trigger RNA or function as global off switches by disrupting the stability or function of the protein partner.
Reconstructing extrachromosomal DNA structural heterogeneity from long-read sequencing data using Decoil
Authors: Giurgiu Mădălina , Wittstruck Nadine , Rodriguez-Fos Elias , Chamorro González Rocío , Brückner Lotte , Krienelke-Szymansky Annabell , Helmsauer Konstantin , Hartebrodt Anne , Euskirchen Philipp , Koche Richard P. , Haase Kerstin , Reinert Knut , Henssen Anton G.
Published: August 2024

Circular extrachromosomal DNA (ecDNA) is a form of oncogene amplification found across cancer types and associated with poor outcome in patients. ecDNA can be structurally complex and can contain rearranged DNA sequences derived from multiple chromosome locations. As the structure of ecDNA can impact oncogene regulation and may indicate mechanisms of its formation, disentangling it at high resolution from sequencing data is essential. Even though methods have been developed to identify and reconstruct ecDNA in cancer genome sequencing, it remains challenging to resolve complex ecDNA structures, in particular amplicons with shared genomic footprints. We here introduce Decoil, a computational method that combines a breakpoint-graph approach withLASSOregression to reconstruct complex ecDNA and deconvolve co-occurring ecDNA elements with overlapping genomic footprints from long-read nanopore sequencing. Decoil outperforms de novo assembly and alignment-based methods in simulated long-read sequencing data for both simple and complex ecDNAs. Applying Decoil on whole-genome sequencing data uncovered different ecDNA topologies and explored ecDNA structure heterogeneity in neuroblastoma tumors and cell lines, indicating that this method may improve ecDNA structural analyses in cancer.
Disorder-induced topological quantum phase transitions in multigap Euler semimetals
Authors: Jankowski Wojciech J. , Noormandipour Mohammadreza , Bouhon Adrien , Slager Robert-Jan
Published: August 2024

We study the effect of disorder in systems having a nontrivial Euler class. As these recently proposed multigap topological phases come about by braiding non-Abelian charged band nodes residing between different bands to induce stable pairs within isolated band subspaces, novel properties may be expected. Namely, a modified stability and critical phases under the unbraiding to metals can arise when the disorder preserves the underlying C2T or PT symmetry on average. Employing elaborate numerical computations, we verify the robustness of associated topology by evaluating the changes in the average densities of states and conductivities for different types of disorders. Upon performing a scaling analysis around the corresponding quantum critical points, we retrieve a universality for the localization length exponent of ν=1.4±0.1 for Euler-protected phases, relating to two-dimensional percolation models. We generically find that quenched disorder drives Euler semimetals into critical metallic phases. Finally, we show that magnetic disorder can also induce topological transitions to quantum anomalous Hall plaquettes with local Chern numbers determined by the initial value of the Euler invariant.

Published by the American Physical Society
2024
Investigation on the
Ω(2012)
from QCD sum rules
Authors: Su Niu , Chen Hua-Xing , Gubler Philipp , Hosaka Atsushi
Published: August 2024

We study the recently observed Ω(2012) baryon in quantum chromodynamics (QCD) sum rules. We construct the P-wave Ω baryon currents with a covariant derivative, and perform spin projection to obtain the currents with total spin 1/2 and 3/2. We then apply the parity-projected QCD sum rules to separate the contributions of the positive and negative parity states. We extract the masses of JP=1/2− and 3/2− states to be M1/2−=2.07−0.07+0.07  GeV and M3/2−=2.05−0.10+0.09  GeV. Both results are in good agreement with the experimental result. Therefore, it is likely that the Ω(2012) is a negative parity state, which is interpreted as a P-wave excited state in the quark model. However, its spin is not determined in the present analysis, which can be done by detailed study on its decay properties.

Published by the American Physical Society
2024
Dark matter relic density in strongly interacting dark sectors with light vector mesons
Authors: Bernreuther Elias , Hemme Nicoline , Kahlhoefer Felix , Kulkarni Suchita
Published: August 2024

Stable dark matter particles may arise as pseudo-Goldstone bosons from the confinement of dark quarks interacting via a non-Abelian gauge force. Their relic abundance is determined not by annihilations into visible particles but by dark pion number-changing processes within the dark sector, such as 3πD→2πD. However, if the dark vector mesons ρD are light enough for 3πD→πDρD annihilations to be kinematically allowed, this process dominates and significantly delays freeze-out. As a result, the preferred dark matter mass scale increases and bounds from the Bullet Cluster can be evaded.

Published by the American Physical Society
2024
Ωc→π+(π0,η)πΞ*
,
π+(π0,η)K¯Σ*
reactions and the two
Ξ(1820)
states
Authors: Liang Wei-Hong , Molina Raquel , Oset Eulogio
Published: August 2024

We have studied the Ωc→π+(π0,η)πΞ* and Ωc→π+(π0,η)K¯Σ* decays, where the final πΞ* or K¯Σ* comes from the decay of two resonances around the nominal Ξ(1820), which are generated from the interaction of coupled channels made of a pseudoscalar and a baryon of the decuplet. The πΞ* mass distributions obtained in the six different reactions studied are quite different, and we single out four of them, which are free of a tree level contribution, showing more clearly the effect of the resonances. The lower mass resonance is clearly seen as a sharp peak, but the higher mass resonance manifests itself through an interference with the lower one that leads to a dip in the mass distribution around 1850 MeV. Such a feature is similar to the dip observed in the S-wave ππ cross section around the 980 MeV coming from the interference of the f0(500) and f0(980) resonances. Its observation in coming upgrades of present facilities will shed light on the existence of these two resonances and their nature. On the other hand, when the Ωc→π+(π0,η)K¯Σ* reactions are studied, both peaks are observed.

Published by the American Physical Society
2024
Astrophysical constraints from synchrotron emission on very massive decaying dark matter
Authors: Munbodh Pankaj , Profumo Stefano
Published: August 2024

If the cosmological dark matter (DM) couples to Standard Model (SM) fields, it can decay promptly to SM states in a highly energetic hard process, which subsequently showers and hadronizes to give stable particles including e±, γ, p±, and νν¯ at lower energy. If the DM particle is very heavy, the high-energy e±, due to the Klein-Nishina cross section suppression, preferentially lose energy via synchrotron emission which, in turn, can be of unusually high energies. Here, we present previously unexplored bounds on heavy decaying DM up to the Planck scale, by studying the synchrotron emission from the e± produced in the ambient Galactic magnetic field. In particular, we explore the sensitivity of the resulting constraints on the DM decay width to (i) different SM decay channels, to (ii) the Galactic magnetic field configurations, and to (iii) various different DM density profiles proposed in the literature. We find that constraints from the synchrotron component complement and improve on constraints from very high-energy cosmic-ray and gamma-ray observatories targeting the prompt emission when the DM is sufficiently massive, most significantly for masses in excess of 1012  GeV.

Published by the American Physical Society
2024
sl(2,C)×D
symmetry and conformal primary basis for massless fields
Authors: Chen Yuan , Li Mingfeng , Shi Kai , Zhang Hongbao , Zhang Jingchao
Published: August 2024

Alternative to the embedding formalism, we provide a group theoretic approach to the conformal primary basis for the massless field with arbitrary helicity. To this end, we first point out that sl(2,C) isometry gets enhanced to sl(2,C)×D symmetry for the solution space of the massless field with D the bulk dilatation. Then, associated with sl(2,C)×D symmetry, we introduce the novel quadratic Casimirs and relevant tensor/spinor fields to derive two explicit constraints on the bulk dilatation and sl(2,C) Casimirs. With this, we further argue that the candidate conformal primary basis can be constructed out of the infinite tower of the descendants of the left and right highest (lowest) conformal primary wave function of sl(2,C) Lie algebra, and the corresponding celestial conformal weights are determined by the bulk scaling dimension through solving out the exact on-shell conformal primary wave functions, where on top of the two kinds of familiar-looking on-shell conformal primary wave functions, we also obtain another set of independent on-shell conformal primary wave functions for the massless field with helicity |s|≥1. In passing, we also develop the relationship between the four-dimensional Lorentz Lie algebra and two-dimensional conformal Lie algebra from scratch, and present an explicit derivation for the two important properties associated with the conformal primary wave functions.

Published by the American Physical Society
2024
All-loop soft theorem for pions
Authors: Bartsch Christoph , Kampf Karol , Novotný Jiří , Trnka Jaroslav
Published: August 2024

In this paper we discuss a generalization of the Adler zero to loop integrands in the planar limit of the SU(N) nonlinear sigma model (NLSM). The Adler zero for integrands is violated starting at the two-loop order and is only recovered after integration. Here we propose a soft theorem satisfied by loop integrands with any number of loops and legs. This requires a generalization of NLSM integrands to an off shell framework with certain deformed kinematics. Defining an , we identify a simple nonvanishing soft behavior of integrands, which we call the . We find that the proposed soft theorem is satisfied by the “surface” integrand of Arkani-Hamed and Figueiredo [], which is obtained from the shifted Trφ3 surfacehedron integrand. Finally, we derive an on shell version of the algebraic soft theorem that takes an interesting form in terms of self-energy factors and lower-loop integrands in a mixed theory of pions and scalars.

Published by the American Physical Society
2024
Entanglement entropy, phase transition, and island rule for Reissner-Nordström-AdS black holes
Authors: Lin Shu-Yi , Yu Ming-Hui , Ge Xian-Hui , Tian Li-Jun
Published: August 2024

This study focuses on the examination of the island rule within the context of four-dimensional Reissner-Nordström-anti-de Sitter (4D RN-AdS) black holes, illuminating the intricate relationship between the entanglement entropy and phase transitions of black holes. The entanglement entropy of 4D RN-AdS black holes follows the anticipated linear growth pattern before ultimately declining to a constant value, in accordance with the well-established Page curve. The novelty of this study lies in the examination of the influence, previously unexplored, of the first-order phase transition on the shape and evolution of the Page curve in situations involving both eternal and evaporating black holes. Despite the morphological alterations of the curve induced by the transition, the inherent unitarity of the system persists. As the evaporation progresses, the Page curve displays diverse configurations, unveiling phenomena that are novel and defies traditional expectations, thereby enriching our comprehension of the thermodynamics of black holes interlinked with quantum information.

Published by the American Physical Society
2024
Search for two-body
B
meson decays to
Λ0
and
Ωc(*)0
Authors: Savinov V. , Adachi I. , Ahn J. K. , Aihara H. , Asner D. M. , Atmacan H. , Ayad R. , Banerjee Sw. , Bennett J. , Bessner M. , Bhardwaj V. , Biswas D. , Bobrov A. , Bodrov D. , Borah J. , Bračko M. , Branchini P. , Browder T. E. , Budano A. , Červenkov D. , Chang M.-C. , Chang P. , Cheon B. G. , Cho K. , Choi S.-K. , Choi Y. , Choudhury S. , Dash N. , De Nardo G. , De Pietro G. , Dhamija R. , Di Capua F. , Dingfelder J. , Doležal Z. , Dubey S. , Ecker P. , Epifanov D. , Farino M. , Ferlewicz D. , Fulsom B. G. , Gaur V. , Giri A. , Goldenzweig P. , Graziani E. , Gu T. , Guan Y. , Gudkova K. , Hadjivasiliou C. , Hayashii H. , Hazra S. , Hedges M. T. , Hou W.-S. , Inami K. , Ipsita N. , Ishikawa A. , Itoh R. , Iwasaki M. , Jacobs W. W. , Jin Y. , Kalita D. , Kim C. H. , Kim D. Y. , Kim K.-H. , Kim Y.-K. , Kinoshita K. , Kodyš P. , Korobov A. , Korpar S. , Kovalenko E. , Križan P. , Krokovny P. , Kuhr T. , Kumar R. , Kumita T. , Kuzmin A. , Kwon Y.-J. , Lai Y.-T. , Lam T. , Lange J. S. , Li L. K. , Li Y. , Li Y. B. , Li Gioi L. , Libby J. , Liventsev D. , Luo T. , Ma Y. , Masuda M. , Matsuda T. , Maurya S. K. , Meier F. , Merola M. , Nakamura I. , Nakao M. , Natkaniec Z. , Nayak L. , Nayak M. , Nishida S. , Ogawa S. , Ono H. , Pakhlov P. , Pakhlova G. , Pardi S. , Park H. , Park J. , Park S.-H. , Passeri A. , Patra S. , Pedlar T. K. , Pestotnik R. , Piilonen L. E. , Podobnik T. , Prencipe E. , Prim M. T. , Russo G. , Sandilya S. , Santelj L. , Schnell G. , Schwanda C. , Seino Y. , Senyo K. , Shan W. , Sharma C. , Shiu J.-G. , Solovieva E. , Starič M. , Sumihama M. , Takizawa M. , Tamponi U. , Tanida K. , Tenchini F. , Tiwary R. , Trabelsi K. , Uchida M. , Unno Y. , Uno S. , Varvell K. E. , Wang E. , Watanuki S. , Won E. , Xu X. , Yabsley B. D. , Yan W. , Yin J. H. , Yuan C. Z. , Yuan L. , Yusa Y. , Zhang Z. P. , Zhilich V. , Zhukova V. ,   The Belle Collaboration
Published: August 2024

We report the results of the first search for Standard Model and baryon-number-violating two-body decays of the neutral B mesons to Λ0 and Ωc(*)0 using 711  fb−1 of data collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e− collider. We observe no evidence of signal from any such decays and set 95% confidence-level upper limits on the products of B0 and B¯0 branching fractions for these two-body decays with B(Ωc0→π+Ω−) in the range between 9.5×10−8 and 31.2×10−8.

Published by the American Physical Society
2024