bluuebunny/crossref_metadata_2025 huggingface dataset:
G-quadruplexes are a source of vulnerability inBRCA2deficient granule cell progenitors and medulloblastoma
Authors: Keahi Danielle L. , Sanders Mathijs A. , Paul Matthew R. , Webster Andrew L. H. , Fang Yin , Wiley Tom F. , Shalaby Samer , Carroll Thomas S. , Chandrasekharappa Settara C. , Sandoval-Garcia Carolina , MacMillan Margaret L. , Wagner John E. , Hatten Mary E. , Smogorzewska Agata
Published: July 2024

Biallelic pathogenic variants in the essential DNA repair geneBRCA2causes Fanconi anemia, complementation group FA-D1. Patients in this group are highly prone to develop embryonal tumors, most commonly medulloblastoma arising from the cerebellar granule cell progenitors (GCPs). GCPs undergo high proliferation in the postnatal cerebellum under SHH activation, but the type of DNA lesions that require the function of the BRCA2 to prevent tumorigenesis remains unknown. To identify such lesions, we assessed both GCP neurodevelopment and tumor formation using a mouse model with deletion of exons three and four ofBrca2in the central nervous system, coupled with globalTrp53loss.Brca2Δex3-4;Trp53-/-animals developed SHH subgroup medulloblastomas with complete penetrance. Whole-genome sequencing of the tumors identified structural variants with breakpoints enriched in areas overlapping G-quadruplexes (G4s).Brca2-deficient GCPs exhibited decreased replication speed in the presence of the G4-stabilizer pyridostatin.Pif1helicase, which resolves G4s during replication, was highly upregulated in tumors, andPif1knockout in primary MB tumor cells resulted in increased genome instability upon pyridostatin treatment. These data suggest that G4s may represent sites prone to replication stalling in highly proliferative GCPs and without BRCA2, G4s become a source of genome instability. Tumor cells upregulate G4-resolving helicases to facilitate rapid proliferation through G4s highlighting PIF1 helicase as a potential therapeutic target for treatment ofBRCA2-deficient medulloblastomas.
Evolution of fast-growing piscivorous herring in the young Baltic Sea
Authors: Goodall Jake , Pettersson Mats E. , Bergström Ulf , Cocco Arianna , Delling Bo , Heimbrand Yvette , Karlsson Magnus , Larsson Josefine , Waldetoft Hannes , Wallberg Andreas , Wennerström Lovisa , Andersson Leif
Published: July 2024

The circumstances under which species diversify to genetically distinct lineages is a fundamental question in biology1. Atlantic herring is an extremely abundant zooplanktivorous species that is subdivided into multiple ecotypes that differ regarding spawning time and genetic adaption to local environmental conditions such as temperature, salinity, and light conditions2,3. Here we show using whole genome analysis that multiple populations of piscivorous (fish-eating) herring have evolved sympatrically after the colonization of the brackish Baltic Sea within the last 8,000 years postglaciation. The piscivorous ecotype grows faster, and is much larger and less abundant than the zooplanktivorous Baltic herring. Lesions of the gill rakers in the piscivorous ecotype indicated incomplete adaptation to a fish diet. This niche expansion of herring in the young Baltic Sea with its paucity of piscivorous species suggests that empty niche space is more important than geographic isolation for the evolution of biodiversity.
Genetic characterization of the complete genome of a strain of Chikungunya virus circulating in Brazil: a strategy for the surveillance and control of Arboviral diseases with epidemic potential in Latin America.
Authors: Villarreal Julio Rafael Guillermo , Sepulveda Ayala Juan David , Pabon Mir David Alejandro , Zapata Arango Juam Felipe , Palacio Estrada Marcela , Patino Mejia Andres Felipe , Zea Restrepo Santiago
Published: July 2024

Chikungunya virus (CHIKV) is a positive-sense single-stranded RNA virus that belongs to the Alphavirus genus of the Togaviridae family. It is mainly transmitted by mosquitoes Aedes aegypti and albopictus. Its genome encodes four non-structural proteins (NSP 1-4 encoded at the 5' end) and three structural proteins (C, E1 and E2 structural proteins encoded at the 3' end). Four lineages of this virus have been identified, namely the lineages from 1) West Africa, 2) East, Central and South Africa (ECSA), 3) Asia (AL) and 4) Indian Ocean (IOL). CHIKV is an endemic arbovirus circulating in 51 countries in the Americas. The clinical manifestations attributed to it are: high fever, rash, myalgia and episodes of arthralgia, which consequently lead to chronic pain and disability, especially in the joints. Whole genome sequencing of the Chikungunya virus is essential to understand its biology, evolution and spread, and to develop effective prevention, diagnosis and treatment strategies. This information is essential to combat the disease and minimize its impact on public health. For these reasons, the complete genome of the Chikungunya virus BR33, identified in the northeastern city of Recife, in the state of Pernambuco, Brazil, was sequenced. The genome has a size of 11,601 nucleotides and fragments that code for two polyproteins. A phylogenic analysis was performed indicating that the recent Brazilian strain of CHIKV belongs to the East, Central and Southern Africa (ECSA) lineage. This phylogenetic identification is important because this particular genotype has been associated with greater damage and clinical severity, in addition to the fact that this ECSA lineage has a wide range of genomic diversity. Until 2016, CHIKV was directly associated with travel and transmission was limited. Subsequently, in the State of Pernambuco, Brazil, the introduction of a new ECSA lineage was identified, which corresponds to the one identified in this study and which generated the largest outbreak. New CHIKV outbreaks are very likely in the near future due to the abundance of competent vectors in Brazil and a susceptible population, exposing more than 11 million inhabitants to an increasing risk of infection.
Centennial recovery of recent human-disturbed forests
Authors: Rodríguez-Uña Asun , Cruz-Alonso Verónica , López-López José A. , Moreno-Mateos David
Published: July 2024

International commitments are challenging countries to restore their degraded lands, particularly forests. These commitments require global assessments of recovery timescales and trajectories of different forest attributes to inform restoration strategies. We use a meta-chronosequence approach including 125 forest chronosequences to reconstruct past (c. 300 years), and model future recovery trajectories of forests recovering from agriculture and logging impacts. We found recovering forests significantly differed from undisturbed ones after 150 years and projected that difference to remain for up to 218 (38-745) or 494 (92-2,039) years for ecosystem attributes like nitrogen stocks or species similarity, respectively. These conservative estimates, however, do not capture the complexity of forest ecosystems. A centennial recovery of forests requires strategic, unprecedented planning to deliver a restored world.
SMYD5 is a ribosomal methyltransferase that catalyzes RPL40 lysine methylation to enhance translation output and promote hepatocellular carcinoma
Authors: Miao Bisi , Ge Ling , He Chenxi , Wang Xinghao , Wu Jibo , Li Xiang , Chen Kun , Wan Jinkai , Xing Shenghui , Ren Lingnan , Shi Zhennan , Flores Natasha M. , Liang Zhihui , Xu Xinyi , Wang Ruoxin , Cheng Jingdong , Mao Yuanhui , Mazur Pawel K. , Cai Jiabin , Lan Fei
Published: July 2024

While lysine methylation is well-known for regulating gene expression transcriptionally, its implications in translation have been largely uncharted. Trimethylation at lysine 22 (K22me3) on RPL40, a core ribosomal protein located in the GTPase activation center (GAC), was first reported 27 years ago. Yet, its methyltransferase and role in translation remain unexplored. Here, we report that SMYD5 has robustin vitroactivity toward RPL40 K22 and primarily catalyzes RPL40 K22me3 in cells. The loss of SMYD5 and RPL40 K22me3 leads to reduced translation output and disturbed elongation as evidenced by increased ribosome collisions. SMYD5 and RPL40 K22me3 are upregulated in hepatocellular carcinoma (HCC) and negatively correlated with patient prognosis. Depleting SMYD5 renders HCC cells hypersensitivity to mTOR inhibition in both 2D and 3D cultures. Additionally, the loss of SMYD5 markedly inhibits HCC development and growth in both genetically engineered mouse (GEM) and patient-derived xenograft (PDX) models, with the inhibitory effect in the PDX model further enhanced by concurrent mTOR suppression. Our findings reveal a novel role of the SMYD5 and RPL40 K22me3 axis in translation elongation and highlight the therapeutic potential of targeting SMYD5 in HCC, particularly with concurrent mTOR inhibition. This work also broadens the understanding of lysine methylation, extending its significance from transcriptional regulation to translational control.
Dengue virus structural proteins are expressed on the surface of DENV-infected cells and are a target for antibody-dependent cellular phagocytosis
Authors: Waldran Mitchell J. , Kurtz Elizabeth A. , Gebo Chad J. , Rooney Timothy J. , Middleton Frank A. , Roy Nathan H. , Currier Jeffrey R. , Waickman Adam T.
Published: July 2024

Dengue virus (DENV) is an arboviral pathogen found in over 100 countries and a source of significant morbidity and mortality. While the mechanisms underpinning the pathophysiology of severe dengue are incompletely understood, it has been previously suggested that antibodies directed against the DENV envelope (E) protein can facilitate antibody dependent enhancement (ADE) of the infection, increasing the number of infected cells and the severity of infection in an exposed individual. Accordingly, there is interest in defining mechanisms for directly targeting DENV-infected cells for immunologic clearance, an approach that bypasses the risk of ADE. We have previously demonstrated that antibodies specific for DENV non-structural protein 1 (NS1) can opsonize and facilitate the phagocytic clearance of DENV infected cells. However, it is currently unclear if other DENV antigens are expressed on the surface of infected cells, and if these antigens can be targeted by antibody-dependent clearance mechanisms. In this study, we demonstrate that DENV structural proteins are expressed on the surface of DENV-infected cells, and that these antigens can be opsonized by both DENV-immune sera and monoclonal antibodies. In addition, DENV E-specific antibodies can facilitate phagocytic uptake of DENV-infected cells, resulting in the target-cell membrane localizing to endosomes of the engulfing phagocyte. Notably, no DENV genetic material was observed localizing to the engulfing phagocyte, suggesting that horizontal transfer of DENV from the infecting cell is an unlikely occurrence. In their totality, these data reinforce the concept that DENV E-reactive antibodies have a multifaceted role in DENV immunity and pathogenesis beyond neutralization and/or infection-enhancement.
Continuous Monitoring of Glucose and Oxygen using an Insertable Biomaterial-based Multianalyte Barcode Sensor
Authors: Pradhan Ridhi , Chimene David , Ko Brian S. , Goncharov Artem , Ozcan Aydogan , McShane Michael J.
Published: July 2024

Chronic diseases including diabetes, cardiovascular diseases, and microvascular complications contribute significantly to global morbidity and mortality. Multiplexing technologies offer a promising approach for the simultaneous detection and management of comorbidities, providing comprehensive disease insights. In this work, we describe a miniaturized optical “barcode” sensor with high biocompatibility for continuous monitoring of glucose and oxygen. This enzymatic sensor relies on oxygen consumption in proportion to local glucose levels and the phosphorescence reporting of tissue oxygen with a lifetime-based probe. The sensor was designed to operate in a tissue environment with low levels of dissolved oxygen. The barcode sensor consists of a poly(ethylene) glycol diacrylate (PEGDA) hydrogel with four discrete compartments separately filled with glucose or oxygen-sensing phosphorescent microparticles. We evaluated the response of the barcode hydrogels to fluctuating glucose levels over the physiological range under low oxygen conditions, demonstrating controlled tuning of dynamic range and sensitivity. Moreover, the barcode sensor exhibited remarkable storage stability over 12 weeks, along with full reversibility and excellent reproducibility (∼6% variability in phosphorescence lifetime). Electron beam sterilization had a negligible impact on the glucose response of the barcode sensors. Furthermore, our investigation revealed minimal phosphorescence lifetime changes in oxygen compartments while exhibiting increased lifetime in glucose-responsive compartments when subjected to alternating glucose concentrations (0 and 200 mg/dL), showcasing the sensor’s multianalyte sensing capabilities without crosstalk between compartments. Additionally, evaluation of tissue response to sensors inserted in pigs revealed appropriate biocompatibility of the barcodes.
Metabolomics profiling reveals association of fermented herbal feed additive, growth performance and gut microbiota in piglets
Authors: Xiao Ruiming , Wang Lingling , Tang Zhiqiang , Qian Xueqiao , Wang Jian , Lian Yingli , Tang Jiayi , Xu Jiarou , Lin Ying , Shi Baojun , Xu Pan , Xiong Qiongsi
Published: July 2024

Fermented Chinese medicine (FCM), as a functional feed additive, has been widely recognized to play a significant role in protecting the intestinal health of piglets and enhancing productive performance. However, the relationship between the active components of FCM, gut microbiota, and their beneficial effects on animal performance remains unclear. In this study, metabolomics analysis revealed a significant increase in the main contents of lactic acid and propionic acid in FCM, while most glycosides and their derivatives decreased after three days of microbial fermentation. Subsequently, piglets were fed a basic diet supplemented with 1% FCM, while the control group received only the basic diet. The results indicated a significant increase in feed intake and average daily gain within 14 days (P<0.05) due to FCM supplementation. Additionally, FCM significantly improved feed efficiency from 1.76 to 1.50 (P<0.05). Meanwhile, piglets in the FCM group exhibited significantly lower frequencies of diarrhea and coughing, indicating better health. Moreover, high-throughput sequencing analysis revealed higher abundances ofLactobacillus agilis,Megasphaera elsdenii,Ligilactobacillus, andVeillonellaceaein piglets fed with FCM. In summary, FCM increased the content of active ingredients through microbial fermentation and regulated the intestinal microbiota to improve the health of piglets. FCM offers a promising potential for enhancing production performance and economic efficiency in the livestock industry.
Pollen Trapping As Honeybees Pollination Management and Identification of Dominant Pollinators of Guizotia abyssinica (L.f)
Authors: Jilo Kasim Roba , Yadeta Gemmechis Legesse , Gemmeda Tolera Kumsa
Published: July 2024

Pollination is one of the most fascinating aspects of insect-plant interactions. Pollen is the male reproductive element of flowering plants, gathered by foraging Honeybees from the male parts of flowering plants called the anther. Guizotia abyssinica (L.f) is an important oilseed crop cultivated in Ethiopia and India, which belongs to the family Asteraceae. Although self-incompatibility is found in Guizotia abyssinica, a higher seed set is experienced in places with an active Honeybees population. Agricultural practices usually focus on inputs such as fertilizer application to improve seed yield of Guizotia abyssinica. However, these practices have little effect on yield if the availability of insect pollination is too low. To fill this gap, an experiment was carried out at Dandi district, West Shao zone, Oromia, Ethiopia to see the effect of Honeybees pollination management as an agronomic input. Pollination management of Honeybees was tested under feeding and non-feeding of colonies management. Pollen was trapped with and without sugar syrup feeding. The results discovered that Honeybees fed sugar syrup collected much more pollen than colonies not fed sugar syrup. The proportion of Guizotia abyssinica pollen collected through sugar syrup feeding of the colony was greater (62.2%), compared to the proportion of Guizotia abyssinica pollen trapped without sugar syrup feeding (37.8%). This indicates that sugar syrup feeding enhances the collection of pollen and probably enhances the pollination efficiency of Honeybees since they visit frequently to fulfill their daily protein requirement of pollen. Therefore, Honeybees pollination services should be included as one of the agronomic inputs with sugar syrup feeding as pollination management that might increase the yield of Guizotia abyssinica since it increases visiting frequency.
Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC
Authors: Abdelazeem Khalid N.M. , Nguyen Diemmy , Corbo Sophia , Darragh Laurel B. , Matsumoto Mike W. , Van Court Benjamin , Neupert Brooke , Yu Justin , Olimpo Nicholas A. , Osborne Douglas Grant , Gadwa Jacob , Ross Richard B. , Nguyen Alexander , Bhatia Shilpa , Kapoor Mohit , Friedman Rachel S. , Jacobelli Jordan , Saviola Anthony J. , Knitz Michael W. , Pasquale Elena B. , Karam Sana D.
Published: July 2024

The EphB4-ephrinB2 signaling axis has been heavily implicated in metastasis across numerous cancer types. Our emerging understanding of the dichotomous roles that EphB4 and ephrinB2 play in head and neck squamous cell carcinoma (HNSCC) poses a significant challenge to rational drug design. We find that EphB4 knockdown in cancer cells enhances metastasis in preclinical HNSCC models by augmenting immunosuppressive cells like T regulatory cells (Tregs) within the tumor microenvironment. EphB4 inhibition in cancer cells also amplifies their ability to metastasize through increased expression of genes associated with epithelial mesenchymal transition and hallmark pathways of metastasis. In contrast, vascular ephrinB2 knockout coupled with radiation therapy (RT) enhances anti-tumor immunity, reduces Treg accumulation into the tumor, and decreases metastasis. Notably, targeting the EphB4-ephrinB2 signaling axis with the engineered EphB4 ligands EFNB2-Fc-His and Fc-TNYL-RAW-GS reduces local tumor growth and distant metastasis in a preclinical model of HNSCC. Our data suggest that targeted inhibition of vascular ephrinB2 while avoiding inhibition of EphB4 in cancer cells could be a promising strategy to mitigate HNSCC metastasis.
Transcriptome-Wide Root Causal Inference
Authors: Strobl Eric V. , Gamazon Eric R.
Published: July 2024

Root causal genes correspond to the first gene expression levels perturbed during pathogenesis by genetic or non-genetic factors. Targeting root causal genes has the potential to alleviate disease entirely by eliminating pathology near its onset. No existing algorithm discovers root causal genes from observational data alone. We therefore propose the Transcriptome-Wide Root Causal Inference (TWRCI) algorithm that identifies root causal genes and their causal graph using a combination of genetic variant and unperturbed bulk RNA sequencing data. TWRCI uses a novel competitive regression procedure to annotate cis and trans-genetic variants to the gene expression levels they directly cause. The algorithm simultaneously recovers a causal ordering of the expression levels to pinpoint the underlying causal graph and estimate root causal effects. TWRCI outperforms alternative approaches across a diverse group of metrics by directly targeting root causal genes while accounting for distal relations, linkage disequilibrium, patient heterogeneity and widespread pleiotropy. We demonstrate the algorithm by uncovering the root causal mechanisms of two complex diseases, which we confirm by replication using independent genome-wide summary statistics.
Evaluation of false positive and false negative errors in targeted next generation sequencing
Authors: Moon Youngbeen , Kim Young-Ho , Kim Jong-Kwang , Hong Chung Hwan , Kang Eun-Kyung , Choi Hye Won , Lee Dong-eun , Kim Tae-Min , Heo Seong Gu , Han Namshik , Hong Kyeong-Man
Published: July 2024

Background

Although next generation sequencing (NGS) has been adopted as an essential diagnostic tool in various diseases, NGS errors have been the most serious problem in clinical implementation. Especially in cancers, low level mutations have not been easy to analyze, due to the contaminating normal cells and tumor heterozygosity.

Results

In targeted NGS (T-NGS) analyses for reference-standard samples containing mixtures of homozygote H. mole DNA with blood genomic DNA at various ratios from four certified NGS service providers, large differences in the lower detection limit of variants (16.3 times, 1.51∼24.66%) and the false positive (FP) error rate (4280 times, 5.814 x 10−4∼1.359 x 10−7) were found. Employment of the commercially available Dragen system for bioinformatic analyses reduced FP errors in the results from companies BB and CC, but the errors originating from the NGS raw data persisted. Bioinformatic conditional adjustment to increase sensitivity (less than 2 times) led to a much higher FP error rate (610∼8200 times). In addition, problems such as biased preferential reference base calls during bioinformatic analysis and high-rate FN errors in HLA regions were found in the NGS analysis.

Conclusion

T-NGS results from certified NGS service providers can be quite various in their sensitivity and FP error rate, suggesting the necessity of further quality controls for clinical implementation of T-NGS. The present study also suggests that mixtures of homozygote and heterozygote DNAs can be easily employed as excellent reference-standard materials for quality control of T-NGS.
A deep learning-based multiscale integration of spatial omics with tumor morphology
Authors: Schmauch Benoît , Herpin Loïc , Olivier Antoine , Duboudin Thomas , Dubois Rémy , Gillet Lucie , Schiratti Jean-Baptiste , Di Proietto Valentina , Le Corre Delphine , Bourgoin Alexandre , Taïeb Pr. Julien , Emile Pr. Jean-François , Fridman Pr. Wolf H. , Pronier Elodie , Laurent-Puig Pr. , Durand Eric Y.
Published: July 2024

Spatial Transcriptomics (spTx) offers unprecedented insights into the spatial arrangement of the tumor microenvironment, tumor initiation/progression and identification of new therapeutic target candidates. However, spTx remains complex and unlikely to be routinely used in the near future. Hematoxylin and eosin (H&E) stained histological slides, on the other hand, are routinely generated for a large fraction of cancer patients. Here, we present a novel deep learning-based approach for multiscale integration of spTx with tumor morphology (MISO). We trained MISO to predict spTx from H&E on a new unpublished dataset of 72 10X Genomics Visium samples, and derived a novel estimate of the upper bound on the achievable performance. We demonstrate that MISO enables near single-cell-resolution, spatially-resolved gene expression prediction from H&E. In addition, MISO provides an effective patient representation framework that enables downstream predictive tasks such as molecular phenotyping or MSI prediction.
An Open-Set Semi-Supervised Multi-Task Learning Framework for Context Classification in Biomedical Texts
Authors: Tang Difei , Tam Thomas Yu Chow , Luo Haomiao , Telmer Cheryl A. , Miskov-Zivanov Natasa
Published: July 2024

Objective

In biomedical research, knowledge about the relationships between entities, including genes, proteins, and drugs, is vital for unraveling the complexities of biological processes and intracellular pathway mechanisms. Natural language processing (NLP) and text mining methods have shown great success in biomedical relation extraction (RE). However, extracted relations often lack contextual information like cell type, cell line, and intracellular location, which are crucial components of biological knowledge. Previous studies have treated this problem as a post hoc context-relation association task, which is limited by the absence of a golden standard corpus, leading to error propagation and decreased model performance. To address these challenges, we created CELESTA (Context Extraction through LEarning with Semi-supervised multi-Task Architecture), a framework for biomedical context classification, applicable to both open-set and close-set scenarios.

Methods

To capture the inherent relationships between biomedical relations and their associated contexts, we designed a multi-task learning (MTL) architecture that seamlessly integrates with the semi-supervised learning (SSL) strategies during training. Our framework addresses the challenges caused by the lack of labeled data by assuming that the unlabeled data contain both in-distribution (ID) and out-of-distribution (OOD) data points. Further, we created a large-scale dataset consisting of five context classification tasks by curating two large Biological Expression Language (BEL) corpora and annotating them with our new entity span annotation method. We developed an OOD detector to distinguish between ID and OOD instances within the unlabeled data. Additionally, we utilized the data augmentation method combined with an external database to enrich our dataset, providing exclusive features for models during training process.

Results

We conducted extensive experiments on the dataset, demonstrating the effectiveness of the proposed framework in significantly improving context classification and extracting contextual information with high accuracy. The newly created dataset and code used for this work are publicly available on GitHub (https://github.com/pitt-miskov-zivanov-lab/CELESTA).
Year-round quantification, structure and dynamics of epibacterial communities from diverse macroalgae reveal a persistent core microbiota and strong host specificities
Authors: Brunet Maéva , Le Duff Nolwen , Barbeyron Tristan , Thomas François
Published: July 2024

Macroalgae-bacteria interactions play pivotal ecological roles in coastal ecosystems. Previous characterization of surface microbiota from various macroalgae evidenced fluctuations based on host tissues, physicochemical and environmental parameters. However, the dynamics and degree of similarity of epibacterial communities colonizing phylogenetically distant algae from the same habitat are still elusive. We conducted a year-long monthly epimicrobiota sampling on five algal species inhabiting an English Channel rocky shore:Laminaria digitata,Ascophyllum nodosum,Fucus serratus(brown algae),Palmaria palmata(red alga) andUlvasp. (green alga). To go beyond relative compositional data and estimate absolute variations in taxa abundance, we combined qPCR measurements of 16S rRNA gene copies with amplicon metabarcoding. A core microbiome composed of 10 genera was consistently found year-round on all algae. Notably, the abundant genusGranulosicoccusstood out for being the only one present in all samples and displayed an important microdiversity. Algal host emerged as the primary driver of epibacterial community composition, before seasonality, and bacterial taxa specifically associated with one or several algae were identified. Moreover, the impact of seasons on the epimicrobiota varied depending on algal tissues. Overall, this study provides an extensive characterization of the microbiota of intertidal macroalgae and enhances our understanding of algal-bacteria holobionts.
STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair
Authors: van den Heuvel Diana , Rodríguez-Martínez Marta , van der Meer Paula J. , Moreno Nicolas Nieto , Park Jiyoung , Kim Hyun-Suk , van Schie Janne J.M. , Wondergem Annelotte P. , D’Souza Areetha , Yakoub George , Herlihy Anna E. , Kashyap Krushanka , Boissière Thierry , Walker Jane , Mitter Richard , Apelt Katja , de Lint Klaas , Kirdök Idil , Ljungman Mats , Wolthuis Rob M.F. , Cramer Patrick , Schärer Orlando D. , Kokic Goran , Svejstrup Jesper Q , Luijsterburg Martijn S.
Published: July 2024

Transcription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, and TFIIH around lesion-stalled RNAPII. However, the mechanism and factors required for the transition to downstream repair steps, including RNAPII removal to provide repair proteins access to the DNA lesion, remain unclear. Here, we identify STK19 as a new TCR factor facilitating this transition. Loss of STK19 does not impact initial TCR complex assembly or RNAPII ubiquitylation but delays lesion-stalled RNAPII clearance, thereby interfering with the downstream repair reaction. Cryo-EM and mutational analysis reveal that STK19 associates with the TCR complex, positioning itself between RNAPII, UVSSA, and CSA. The structural insights and molecular modeling suggest that STK19 positions the ATPase subunits of TFIIH onto DNA in front of RNAPII. Together, these findings provide new insights into the factors and mechanisms required for TCR.
Longitudinal sequencing reveals polygenic and epistatic nature of genomic response to selection
Authors: Forsberg Simon K.G. , Melo Diogo , Wolf Scott , Grenier Jennifer K. , Tang Minjia , Henry Lucas P. , Pallares Luisa F. , Clark Andrew G. , Ayroles Julien
Published: July 2024

Evolutionary adaptation to new environments likely results from a combination of selective sweeps and polygenic shifts, depending on the genetic architecture of traits under selection. While selective sweeps have been widely studied, polygenic responses are considered more prevalent but challenging to quantify. The infinitesimal model makes explicit the hypothesis about the dynamics of changes in allele frequencies under selection, where only allelic effect sizes, frequencies, linkage, and gametic disequilibrium matter. Departures from this, like long-range correlations of allele frequency changes, could be a signal of epistasis in polygenic response. We performed anEvolve & Resequenceexperiment inDrosophila melanogasterexposing flies to a high-sugar diet as a source of environmental stress for over 100 generations. We tracked allele frequency changes in >3000 individually sequenced flies as well as population pools and searched for loci under selection by identifying sites with allele frequency trajectories that differentiated selection regimes consistently across replicates. We estimate that at least 4% of the genome was under positive selection, the result of a highly polygenic response. Most of this response was seen as small but consistent allele frequency changes over time, and there were only a few large allele-frequency changes (selective sweeps). We then searched for signatures of selection on pairwise combinations of alleles in the new environment and found several strong signals of putative epistatic interactions across unlinked loci that were consistent across selected populations. Finally, we measured differentially expressed genes (DEGs) across treatments and show that DEGs are enriched for selected SNPs, suggesting a regulatory basis for the selective response. Our results suggest that epistatic contributions to polygenic selective response are common and lead to detectable signatures.
First experimental evidence of a beam-beam long-range compensation using wires in the Large Hadron Collider
Authors: Poyet A. , Bertarelli A. , Carra F. , Fartoukh S. D. , Fuster-Martínez N. , Karastathis N. , Papaphilippou Y. , Pojer M. , Redaelli S. , Rossi A. , Skoufaris K. , Solfaroli Camillocci M. , Sterbini G.
Published: July 2024

In high intensity and high energy colliders, such as the CERN Large Hadron Collider (LHC) and its future high-luminosity upgrade, interactions between the two beams around the different interaction points impose machine performance limitations. In fact, their effect reduces the beam lifetime, and therefore, the collider’s luminosity reach. Those interactions are called beam-beam long-range (BBLR) interactions, and a possible mitigation of their effect using dc wires was proposed for the first time in the early 2000’s. This solution is currently being studied as an option for enhancing the HL-LHC performance. In 2017 and 2018, four demonstrators of wire compensators have been installed in the LHC. A 2-yearlong experimental campaign followed in order to validate the possibility to mitigate the BBLR interactions in the LHC. During this campaign, a proof-of-concept was completed and motivated an additional set of experiments, successfully demonstrating the mitigation of BBLR interactions effects in beam conditions compatible with the operational configuration. This paper reports in detail the preparation of the experimental campaign, including the corresponding tracking simulations and the obtained results, and draws some perspectives for the future.

Published by the American Physical Society
2024
Possible scenario of dynamical chiral symmetry breaking in the interacting instanton liquid model
Authors: Suda Yamato , Jido Daisuke
Published: July 2024

We compute the vacuum energy density as a function of the quark condensate in the interacting instanton liquid model (IILM) and examine the pattern of dynamical chiral symmetry breaking from its behavior around the origin. This evaluation is performed by using simulation results of the IILM. We find that chiral symmetry is broken in the U(1)A anomaly assisted way in the IILM with three-flavor dynamical quarks. We call such a symmetry breaking the anomaly-driven breaking, which is one of the scenarios of chiral symmetry breaking proposed in the context of the chiral effective theories. We also find that the instanton-quark interaction included in the IILM plays a crucial role for the anomaly-driven breaking by comparing the full and the quenched IILM calculations.

Published by the American Physical Society
2024
ALP contribution to the strong
CP
problem
Authors: Enguita V. , Gavela B. , Grinstein B. , Quílez P.
Published: July 2024

We compute the one-loop contribution to the θ¯ parameter of an faxionlike particle (ALP) with CP-odd derivative couplings. Its contribution to the neutron electric dipole moment is shown to be orders of magnitude larger than that stemming from the one-loop ALP contributions to the up- and down-quark electric and chromoelectric dipole moments. This strongly improves existing bounds on ALP-fermion CP-odd interactions and also sets limits on previously unconstrained couplings. The case of a general singlet scalar is analyzed as well. In addition, we explore how the bounds are modified in the presence of a Peccei-Quinn symmetry.

Published by the American Physical Society
2024
Anti-Coulomb ion-ion interactions: A theoretical and computational study
Authors: Wills Alec , Mannino Anthony , Losada Isidro , Mayo Sara G. , Soler Jose M. , Fernández-Serra Marivi
Published: July 2024

The free energy of ion solvation can be decomposed into enthalpic and entropic contributions. This helps one to understand the connection between the dielectric properties and the underlying forces. We present a simple linear-response model of screened charge interactions that provides an alternative understanding of solvation barriers. Moreover, it explains the “anti-Coulomb” interactions (attraction between like-charged ions and repulsion between opposite-charged ions) observed in both simulations and experiments. We show that this is a universal behavior associated to the nonlocal response function of any dielectric or metallic systems.

Published by the American Physical Society
2024
Temporally Correlated Active Forces Drive Segregation and Enhanced Dynamics in Chromosome Polymers
Authors: Brahmachari Sumitabha , Markovich Tomer , MacKintosh Fred C. , Onuchic José N.
Published: July 2024

Understanding the mechanisms governing the structure and dynamics of flexible polymers like chromosomes, especially the signatures of motor-driven active processes, is of great interest in genome biology. We study chromosomes as a coarse-grained polymer model where microscopic motor activity is captured via an additive temporally persistent noise. The active steady state is characterized by two parameters: active force, controlling the persistent-noise amplitude, and correlation time, the decay time of active noise. We find that activity drives correlated motion over long distances and a regime of dynamic compaction into a globally collapsed entangled globule. Diminished topological constraints destabilize the entangled globule, and the active segments trapped in the globule move toward the periphery, resulting in an enriched active monomer density near the periphery. We also show that heterogeneous activity leads to the segregation of the highly dynamic species from the less dynamic one, suggesting a role of activity in chromosome compartmental segregation. Adding activity to experimental-data-derived structures, we find active loci may mechanically perturb and switch compartments established via epigenetics-driven passive self-association. The key distinguishing signatures of activity are enhanced apparent diffusivity, exploration of all the dynamic regimes (subdiffusion, effective diffusion, and superdiffusion) at various lag times, and a broadened distribution of observables like the dynamic exponents.

Published by the American Physical Society
2024
TEMPUS, a Timepix4-based system for the event-based detection of X-rays
Authors: Correa Jonathan , Ignatenko Alexandr , Pennicard David , Lange Sabine , Fridman Sergei , Karl Sebastian , Lohse Leon , Senfftleben Björn , Sergeev Ilya , Velten Sven , Prajapat Deepak , Bocklage Lars , Bromberger Hubertus , Samartsev Andrey , Chumakov Aleksandr , Rüffer Rudolf , von Zanthier Joachim , Röhlsberger Ralf , Graafsma Heinz
Published: July 2024

TEMPUS is a new detector system being developed for photon science. It is based on the Timepix4 chip and, thus, it can be operated in two distinct modes: a photon-counting mode, which allows for conventional full-frame readout at rates up to 40 kfps; and an event-driven time-stamping mode, which allows excellent time resolution in the nanosecond regime in measurements with moderate X-ray flux. In this paper, the initial prototype, a single-chip device, is introduced, and the readout system described. Moreover, and in order to evaluate its capabilities, some tests were performed at PETRA III and ESRF for which results are also presented.
VUV absorption spectra of water and nitrous oxide by a double-duty differentially pumped gas filter
Authors: Bodi Andras , Knurr Jonas , Ascher Patrick , Hemberger Patrick , Bostedt Christoph , Al Haddad Andre
Published: July 2024

The differentially pumped rare-gas filter at the end of the VUV beamline of the Swiss Light Source has been adapted to house a windowless absorption cell for gases. Absorption spectra can be recorded from 7 eV to up to 21 eV photon energies routinely, as shown by a new water and nitrous oxide absorption spectrum. By and large, the spectra agree with previously published ones both in terms of resonance energies and absorption cross sections, but that of N2O exhibits a small shift in the {\tilde{\bf D}} band and tentative fine structures that have not yet been fully described. This setup will facilitate the measurement of absorption spectra in the VUV above the absorption edge of LiF and MgF2 windows. It will also allow us to carry out condensed-phase measurements on thin liquid sheets and solid films. Further development options are discussed, including the recording of temperature-dependent absorption spectra, a stationary gas cell for calibration measurements, and the improvement of the photon energy resolution.
Digital transformation, management efficiency and excess employees − evidence from Chinese listed firms
Authors: Zhang Mengyun , Pu Hongjing , Yu Tianmuzi , Qu Shuyang
Published: July 2024

Purpose

The purpose of this study is to explore the relationship between digital transformation and excess employees. This research investigates the questions of when human−machine synergy can be achieved after a firm goes through digital transformation and whether there will be excess employees in the interim.

Design/methodology/approach

This paper takes A-share listed companies as research object in the period of 2011−2020 and a total of 24,718 samples are obtained. Hypothesis testing and regression analysis are performed in STATA.

Findings

This paper finds a human−machine mismatch in the short term, as evidenced by an increase in the rate of excess employees; however, with the progress of digital transformation, it can drive the achievement of human−machine synergy in the long term, and management efficiency plays a mediating role in this process. Further research showed that the effects of digital transformation on the number of employees, revenue generation per capita and profit generation per capita varied in both the short and long term. In addition, the characteristics of the company affect the relationship between digital transformation and excess employees.

Originality/value

This paper contributes to the understanding of the impacts of digital transformation on the human capital structure of companies at a micro level. It also provides insights into how to improve human capital demand structure through digitalization, thus providing insights into labor market changes.
Exploring the antecedent factors of continuous intention to use mobile money: insights from emerging markets
Authors: Qatawneh Nour , Al-Okaily Aws , Al-Okaily Manaf , Ur Rehman Shafique
Published: July 2024

Purpose

The purpose of this study is to examine the factors that may have an influence on the continuous intention to use mobile money as one of the Financial Technology (FinTech) products beyond the COVID-19 pandemic lockdown period.

Design/methodology/approach

This study has empirically tested the expanded post-acceptance model (Extend-PAM) and the expectation-confirmation model (ECM) to explain the mobile money adoption in Jordan. Data collected were analyzed through partial least squares–structural equation modeling (PLS-SEM).

Findings

The results mainly showed that the quality of administrative services and trust significantly impact confirmation and perceived usefulness. In addition, perceived security and knowledge of mobile money as one of the FinTech services significantly influence users’ confirmation and perceived usefulness. Also, usefulness and satisfaction influence continuous intention. Significant relationships were noted among confirmation, perceived usefulness, satisfaction and continuous intention to use mobile money.

Originality/value

This paper integrates two key theories: the expanded post-acceptance model (Extend-PAM) and the expectation-confirmation model (ECM) in the post-adoption behavior of mobile money. Therefore, this study attempts to fill a literature gap by examining the antecedent factors that influence the continuous intention to use mobile money services in the post-consumption stage.
Proposing a 6R framework promoting circular strategies for platform organizations
Authors: Tewary Abhijeet , Upadhyay Parijat
Published: July 2024

Purpose

This study aims to investigate the connection between the circular economy and sustainable operations management to identify the challenges and opportunities in platform organizations. The study looks at how the stated circular economy strategies (Reduce, Reuse, Repair, Refurbish, Repurpose and Recycle) are integrated across different industries, emphasizing how they align with the e-business model. The research evaluates their contribution to achieving Sustainable Development Goal 12, which focuses on responsible consumption and production.

Design/methodology/approach

A literature review has analyzed CE frameworks, business models and the role of sustainable operations management practices. This study utilized secondary data analysis of platform organizations and insights from case studies to identify patterns, strategies and outcomes. The study also involved practical examinations within organizations, specifically focusing on innovative start-ups.

Findings

The analysis uses the 6R framework (Reduce, Reuse, Repair, Refurbish, Repurpose and Recycle) to uncover valuable insights into organizational practices and highlight the role of platform organizations in promoting and achieving circular economy objectives. The research findings focus on the central importance of data regulation and governance while showcasing sustainable business practices through platform organizations.

Originality/value

This research is significant as it connects circular economy with platform organizations’ business models, emphasizing data regulation, resource efficiency, waste reduction and aligning business practices with Sustainable Development Goal 12.
Unlocking the promise of process mining: shaping perceptions and impact in the public sector
Authors: Racis Serena , Spano Alessandro
Published: July 2024

Purpose

Worldwide challenges impose public organizations to rethink their processes and satisfactorily meet citizens’ needs. Process mining (PM) techniques enable organizations to objectively analyse and improve their processes, by providing higher process transparency and efficiency. However, extant literature on PM applications in the public sector reveals there is still limited evidence on the opportunities and challenges perceived from PM introduction in the public sector, and on PM potential to enhance public sector digital transformation: this study aims to fill these gaps.

Design/methodology/approach

Based on Business Process Management and digital innovation fields of research, we administered a questionnaire to a sample of Italian civil servants working in different public organizations to investigate their perceptions of PM opportunities and challenges and the extent to which it can support public sector digital transformation. A three-level analysis was conducted to inspect findings with different levels of granularity, and results were analysed both descriptively and quantitatively.

Findings

We found a positive attitude towards PM introduction in the public sector, and perceived opportunities and challenges related to both the technical and the social systems. The triangulation between close-ended and open-ended questions suggests that PM could be the missing link between public sector digitalization and digital transformation. These findings can be used by policymakers to develop the best strategies to introduce PM into public organizations and support its adoption, and by researchers to further explore PM role in public sector digital transformation.

Originality/value

Despite PM claiming to push digital transformation, it is not clear if it is also true for public sector organizations. This paper addresses this gap and it is among the first attempts to explore PM from civil servants’ viewpoint to investigate their perceptions of PM opportunities and challenges, as well as the variables that influence these perceptions.