bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic markers of adverse lifestyle identified among night shift workers
Authors: Hulls Paige M. , McCartney Daniel L. , Bao Yanchun , Walker Rosie M. , de Vocht Frank , Martin Richard M. , Relton Caroline L. , Evans Kathryn L. , Kumari Meena , Marioni Riccardo E. , Richmond Rebecca C. 
Published: July 2022

AbstractBackgroundEpigenetic changes in the form of DNA methylation (DNAm) may act as biological markers of risk factors or adverse health states. We investigated associations between night shift work and established DNAm predictors of lifestyle, and compared them with those observed between night shift work and self-reported or conventionally-measured phenotypes.MethodsIn two cohort studies, Generation Scotland (GS) (n=7,028) and Understanding Society (UKHLS) (n=1,175), we evaluated associations between night shift work and four lifestyle factors (body mass index, smoking, alcohol, education) using both conventionally-measured phenotypes and DNA methylation-based scores proxying the phenotypes. DNA methylation-based measures of biological ageing were also generated using six established “epigenetic clocks”. Meta-analysis of GS and UKHLS results was conducted using inverse-variance weighted fixed effects.ResultsNight shift work was associated with higher BMI (0.79; 95%CI 0.02, 1.56; p=0.04) and lower education (-0.18; -0.30, -0.07; p=0.002). There was weak evidence of association between night shift work and DNAm scores for smoking (0.06, -0.03, 0.15; p=0.18) and education (-0.24; -0.49, 0.01; p=0.06) in fully adjusted models. Two of the epigenetic age measures demonstrated higher age acceleration among night shift workers (0.80; 0.42, 1.18; p<0.001 for GrimAge and 0.46; 0.00, 0.92; p=0.05 for PhenoAge).ConclusionsNight shift work is associated with phenotypic and DNAm-based measures of lower education. Night shift work was also related to DNAm predictors of smoking and ageing.
Contrasting roles of landscape compositions in shaping functional traits of arthropod community in subtropical vegetable fields
Authors: Zhang Jie , Saqib Hafiz Sohaib Ahmed , Niu Dongsheng , Gavilanez Karla Giovana Guaman , Wang Ao , Yu Deyi , You Minsheng , Pozsgai Gabor , You Shijun 
Published: July 2022

AbstractAgricultural intensification and land use transformation are among the main driving forces of the unprecedented decline of biodiversity and ecosystem services in croplands. Trait-based approaches provide a unique framework to detect the potential mechanisms of how this intensification affects biodiversity and alter ecosystem services. However, the potential relationship between arthropod traits and various types of habitats is still poorly understood, especially in subtropical vegetable agroecosystems.Here, we conducted a trait-based approach to evaluate the variable roles of different habitats on functional trait diversity and the structure of the arthropod community in brassica vegetable crops. Twenty-three conventional cruciferous vegetables fields were sampled over two years in three regions in Fujian, China. We found that the increasing proportion of non-brassica vegetable plantations and water bodies negatively affected the functional diversity of arthropods, whereas forest and grassland habitats showed a positive correlation, indicating habitat filtering for certain traits or trait combinations.This study demonstrates the importance of landscape composition as an ecological filter for vegetable arthropod community, and identifies how the proportion of different habitats selected for or against specific functional traits. Our findings support that increasing forest and grassland areas adjacent to vegetable fields can play a vital role in promoting the functional diversity of arthropod communities. Since the natural enemy assemblages supported by these habitats bear combinations of diverse traits adapted to disturbance, they have the potential to enhance pest suppression in the highly variable environment of vegetable crops.
Multi-omics analyses identify transcription factor interplay in corneal epithelial fate determination and disease
Authors: Smits Jos GA , Cunha Dulce Lima , Amini Maryam , Bertolin Marina , Laberthonnière Camille , Qu Jieqiong , Owen Nicholas , Latta Lorenz , Seitz Berthold , Roux Lauriane N , Stachon Tanja , Ferrari Stefano , Moosajee Mariya , Aberdam Daniel , Szentmary Nora , van Heeringen Simon J. , Zhou Huiqing 
Published: July 2022

AbstractThe transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells, while the non-transparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human limbal stem cells from the cornea and keratinocytes from the epidermis, and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors that define specific cell fates, and established their regulatory hierarchy. Single-cell RNA-seq analyses of the cornea and the epidermis confirmed these shared and cell type-specific transcription factors. Notably, the shared and limbal stem cell-specific transcription factors can cooperatively target genes associated with corneal opacity. Importantly, we discovered thatFOSL2, a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the limbal stem cell fate and its association with corneal opacity.
Single-cell triple-omics uncovers DNA methylation as key feature of stemness in the healthy and ischemic adult brain
Authors: Kremer Lukas PM , Cerrizuela Santiago , Al Shukairi Mohammad Eid , Ellinger Tobias , Straub Jannes , Dehler Sascha , Korkmaz Aylin , Weichenhan Dieter , Plass Christoph , Anders Simon , Martin-Villalba Ana 
Published: July 2022

SummaryStem cells in the adult brain are specialized astrocytes capable of generating neurons and glial cells. While neural stem cells (NSCs) and common astrocytes have clearly distinct functions, they share highly similar transcriptome profiles. How stemness is molecularly encoded is therefore unclear. Here we use single-cell NMT-seq to simultaneously characterize the transcriptome, DNA methylome and chromatin accessibility of astrocytes and the NSC lineage in the healthy and ischemic brain. Our data reveal distinct methylation profiles associated with either astrocyte or stem cell function. Stemness is conferred by methylation of astrocyte genes and demethylation of neurogenic genes that are expressed only later. Surprisingly, ischemic injury unlocks the stemness-methylome in common astrocytes enabling generation of neuroblasts. Furthermore, we show that oligodendrocytes employ Tet-mediated demethylation to regulate expression of myelin-related genes, many of which are abnormally methylated in multiple sclerosis. Overall, we show that DNA methylation is a promising target for regenerative medicine.Abstract Figure
A hybrid approach for predicting transcription factors
Authors: Patiyal Sumeet , Tiwari Palak , Ghai Mohit , Dhapola Aman , Dhall Anjali , Raghava Gajendra P. S. 
Published: July 2022

AbstractTranscription factors (TFs) are essential DNA-binding proteins that regulate the rate of transcription of several genes and controls the expression of genes inside a cell. The prediction of TFs with high precision is important for understanding number of biological processes such as cell-differentiation, intracellular signaling, cell-cycle control. In this study, we developed a hybrid method that combine alignment-based and alignment-free methods for predicting transcription factors with higher accuracy. All models have been trained, tested and evaluated on a large dataset that contain 19406 TFs and 523560 non-TFs protein sequences. In order to avoid biasness in evaluation, dataset is divided in training and validation/independent dataset, where 80% data was used for training and remaining 20% for external validation. In case of alignment-free methods, models are developed based on machine learning techniques using compositional features of a protein. Our best alignment-free model obtained AUC 0.97 on independent dataset. In case of alignment-based method, we used BLAST at different cut-off to predict transcription factors. Though alignment-based method shows excellent performance but unable to cover all transcription factor due to no-hits. In order to combine power of both, we developed a hybrid method that combine alignment-free and alignment-based method; achieved maximum AUC of 0.99 on independent dataset. The method proposed in this study perform better than existing methods. We incorporated the best models in the webserver/standalone package “TransFacPred” (https://webs.iiitd.edu.in/raghava/transfacpred).Key PointsTranscription factors (TFs) are vital DNA-binding proteins.A hybrid method for the prediction of TFs using sequence information.Computer-aided model were developed using machine-learning algorithm to predict TFs.Alignment-based and alignment-free approaches were used for the prediction.A user-friendly webserver, python- and Perl-based standalone package available.
ROR1 plays a critical role in pancreatic tumor-initiating cells with a partial EMT signature
Authors: Yamazaki Masaya , Hino Shinjiro , Usuki Shingo , Miyazaki Yoshihiro , Oda Tatsuya , Nakao Mitsuyoshi , Ito Takaaki , Yamagata Kazuya 
Published: July 2022

AbstractTumor-initiating cells are the major drivers of chemoresistance and relapse, making them attractive targets for cancer therapy. However, the identity of tumor- initiating cells in human pancreatic ductal adenocarcinoma (PDAC) and the key molecules underlying their traits remain poorly understood. Here, we show that a partial epithelial-mesenchymal transition (EMT)-like subpopulation marked by high expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) is the origin of heterogeneous tumor cells in PDAC. We demonstrate that ROR1 depletion suppresses tumor growth, recurrence after chemotherapy, and metastasis. Mechanistically, ROR1 induces the expression of AURKB by activating E2F to enhance PDAC proliferation. Furthermore, epigenomic analyses reveal that ROR1 is transcriptionally dependent on YAP/BRD4 binding at the enhancer region, and targeting this pathway reduces ROR1 expression and prevents PDAC growth. Collectively, our findings reveal a critical role of ROR1high cells as tumor-initiating cells and the functional importance of ROR1 in PDAC progression, thereby highlighting its therapeutic targetability.Graphical abstract
Regular geometry and hexagonal structure of honeycomb results from the optimisation of cylindrical cells built in close proximity
Authors: Gallo Vincent , Bridges Alice D. , Woodgate Joseph L. , Chittka Lars 
Published: July 2022

AbstractThe hexagonal structure of honeycomb maximises storage volume while minimising the amount of wax required for its construction. How honeybee builders achieve this geometry, however, remains unclear. Previously, our group identified behavioural patterns that were triggered in builders when they encountered certain sub-scale features associated with partially constructed comb, which resulted in the alignment of new cells to small concavities and the construction of cell walls between two of these stimuli. This caused new cells to be built in the proper locations without the need for explicit instructions . Here, we investigated whether the hexagonal geometry of honeycomb cells resulted from the dense packing of cells that would otherwise have been circular tubes. We hypothesised that the reaction of a builder to a cell that is not fully enclosed by other cells would be an attempt to maximise the internal space by excavating and re-forming the surrounding walls to create a cylindrical interior.However, the creation of a cylindrical cell would be thwarted by the activities of workers within adjacent cells also acting according to these rules. Eventually an equilibrium will emerge with walls that meet at a junction arranged so that the available angular range (360°) is sub- divided equally between the cells that meet at the junction (typically, internal angles of 120° when three cells meet). To test this hypothesis, we offered wax stimuli to comb-building honeybees, shaped to encourage or to constrain the construction of comb cells, recording the bees’ progress. We found that at an early stage cells could be an irregular shape with curved walls and unequal wall lengths and corner angles, however, when allowed further time and unconstrained access the workers reshaped the cells achieving significantly greater regularity.
Unsupervised machine learning reveals temporal components of gene expression in HeLa cells following release from cell cycle arrest
Authors: Maimon Tom , Trink Yaron , Goldberger Jacob , Kalisky Tomer 
Published: July 2022

ABSTRACTGene expression measurements of tissues, tumors, or cell lines taken over multiple time points are valuable for describing dynamic biological phenomena such as the response to growth factors. However, such phenomena typically involve multiple biological processes occurring in parallel, making it difficult to identify and discern their respective contributions at any time point. Here, we demonstrate the use of unsupervised machine learning to deconvolve a series of time-dependent gene expression measurements into its underlying temporal components. We first downloaded publicly available RNAseq data obtained from synchronized HeLa cells at consecutive time points following release from cell cycle arrest. Then, we used Fourier analysis and Topic modeling to reveal three underlying components and their relative contributions at each time point. We identified two temporal components with oscillatory behavior, corresponding to the G1-S and G2-M phases of the cell cycle, and a third component with a transient expression pattern, associated with the immediate-early response gene program, regulation of cell proliferation, and cervical cancer. This study demonstrates the use of unsupervised machine learning to identify hidden temporal components in biological systems, with potential applications to early detection and monitoring of diseases and recovery processes.
Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibilty in a canine model of elite exercise
Authors: Polyák A. , Topal L. , Prorok J. , Tóth N. , Kohajda Zs. , Déri Sz. , Demeter-Haludka V. , Hegyi P. , Venglovecz V. , Sarusi A. , Ágoston G. , Husti Z. , Zombori-Tóth N. , Gazdag P. , Szlovák J. , Árpádffy-Lovas T. , Naveed M. , Jost N. , Virág L. , Nagy N. , Baczkó I. , Farkas A. S. , Varró A. 
Published: July 2022

ABSTRACTThe health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SCD is poorly understood. While some studies after endurance training have been performed in small animals these have limited translation value.Here, we show that chronic training in a canine model (12 sedentary and 12 trained dogs) that mimics the regime of elite athletes induces electrophysiological remodeling (measured by ECG, patch-clamp and immunocytochemical techniques) resulting in increases of both the trigger and the substrate for ventricular arrhythmias. Thus, 4 months sustained training lengthened ventricular repolarization (QTc: 213.6±2.8 ms vs. 237.1±3.4 ms, n=12; APD90: 370.1±32.7 ms vs. 472.8±29.6 ms, n=25 vs. 29), decreased transient outward potassium current (8.8±0.9 pA/pF vs. 6.4±0.5 pA/pF at 50 mV, n=42 vs. 54) and increased the short term variability of repolarization (17.5±4.0 ms vs. 29.5±3.8 ms, n=18 vs. 27). Left ventricular fibrosis and HCN4 protein expression were also enhanced. These changes were associated with enhanced ectopic activity (number of extrasystoles: 4/hour vs. 366/hour) in vivo and arrhythmia susceptibility (elicited ventricular fibrillation: 3 of 10 sedentary dogs vs. 6 of 10 trained dogs).Our findings provide in vivo, cellular electrophysiological and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmia in an experimental large animal model of endurance training.
Fine-scale measurement of the blind spot borders
Authors: Meermeier Annegret , Lappe Markus , Rifai Katharina , Wahl Siegfried , Rucci Michele 
Published: July 2022

ABSTRACTThe blind spot is both a necessity and a nuisance for seeing. It is the portion of the visual field projecting to where the optic nerve crosses the retina, a region devoid of photoreceptors and hence visual input. The precise way in which vision transitions into blindness at the blind spot border is to date unknown. A chief challenge to map this transition is the incessant movement of the eye, which unavoidably smears measurements across space. In this study, we used high-resolution eye-tracking and state-of-the-art retinal stabilization to finely map the blind spot borders. Participants reported the onset of tiny high-contrast probes that were briefly flashed at precise positions around the blind spot. This method has sufficient resolution to enable mapping of blood vessels from psychophysical measurements. Our data show that, even after accounting for eye movements, the transition zones at the edges of the blind spot are considerable. On the horizontal meridian, the regions with detection rates between 80% and 20% span approximately 25% of the overall width of the blind spot. These borders also vary considerably in size across different axes. These data show that the transition from full visibility to blindness at the blind spot border is not abrupt but occurs over a broad area.
”Evolution of ipsilateral breast cancer decoded by proteogenomics”
Authors: Marchi Tommaso De , Pyl Paul Theodor , Sjöström Martin , Reinsbach Susanne Erika , DiLorenzo Sebastian , Nystedt Björn , Tran Lena , Pekar Gyula , Wärnberg Fredrik , Fredriksson Irma , Malmström Per , Fernö Mårten , Malmström Lars , Malmstöm Johan , Niméus Emma 
Published: July 2022

AbstractIpsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but also associated with an increased risk of distant metastases and breast cancer death. It currently remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies targeting locally recurring breast cancer. Here, we employed a recently developed proteogenomics workflow to analyze a cohort of 27 primary breast cancers and their matched IBTRs by whole genome sequencing, RNA sequencing, and mass spectrometry-based proteomics to define proteogenomic features of tumor evolution. Analysis of mutational signatures, copy number changes, and cancer specific mutations revealed a relationship with estrogen and progesterone receptor statuses and increased levels of genetic change. This in turn altered the re-programming of the transcriptome and proteome towards a recurring molecular disease phenotype with high replicating capacity and a higher degree of genomic instability possibly enhanced by high expression of APOBEC3B. In conclusion, this study defines how primary breast tumors differentially evolve into different ipsilateral recurrent malignancies depending on their key biomarker status, suggesting that further enhancing the genomic instability in some tumors could serve as an alternative treatment option.
Molecular Evolution of Aryl Hydrocarbon Receptor Signaling Pathway Genes
Authors: Bhalla Diksha , van Noort Vera 
Published: July 2022

AbstractThe Aryl hydrocarbon receptor is an ancient transcriptional factor originally discovered as a sensor of dioxin. In addition to its function as receptor of environmental toxins, it plays an important role in development. Although a significant amount of research has been carried out to understand AHR signal transduction pathway and its involvement in species susceptibility to environmental toxins, none of them to date has comprehensively studied its evolutionary origins. Studying evolutionary origins of molecules can inform ancestral relationships of genes. Vertebrate genome has been shaped by two rounds of whole-genome duplications at the base of vertebrate evolution approximately 600 million years ago (Mya), followed by lineage specific gene losses, which often complicate assignment of functional homology. It is crucial to understand evolutionary origins of this transcription factor and its partners, in order to distinguish orthologs from ancient non-orthologous homologs. In this study, we have investigated evolutionary origins of proteins involved in the AHR pathway. Our results provide evidence of gene loss and duplications, crucial for understanding functional connectivity of human and model species. Multiple studies have shown that 2R-ohnologs (genes and proteins that have survived from the 2R-WGD) are enriched in signaling components relevant to developmental disorders and cancer. Our findings provide a link between AHR pathway’s evolutionary trajectory and its possible mechanistic involvement in pathogenesis.
Insight into the evolutionary assemblage of cranial kinesis from a Cretaceous bird
Authors: Wang Min , Stidham Thomas A. , O’Connor Jingmai K. , Zhou Zhonghe 
Published: July 2022

AbstractThe independent movements and flexibility of various parts of the skull, called cranial kinesis, is an evolutionary innovation that is found in living vertebrates only in some squamates and crown birds, and considered to be a major factor underpinning much of the enormous phenotypic and ecological diversity of living birds, the most diverse group of extant amniotes. Compared to the postcranium, our understanding of the evolutionary assemblage of the characteristic modern bird skull has been hampered by sparse fossil records of early cranial materials, with competing hypotheses regarding the evolutionary development of cranial kinesis among early members of the avialans. Here, a detailed three-dimensional reconstruction of the skull of the Early Cretaceous enantiornithine Yuanchuavis kompsosoura allows for its in depth description, including elements that are poorly known among early diverging avialans but are central to deciphering the mosaic assembly of features required for modern avian cranial kinesis. Our reconstruction of the skull shows evolutionary and functional conservation of the temporal and palatal regions by retaining the ancestral theropod dinosaurian configuration within the skull of this otherwise derived and volant bird. Geometric morphometric analysis of the palatine suggests that loss of the jugal process represents the first step in the structural modifications of this element leading to the kinetic crown bird condition. The mixture of plesiomorphic temporal and palatal structures together with a derived avialan rostrum and postcranial skeleton encapsulated in Yuanchuavis manifests the key role of evolutionary mosaicism and experimentation in early bird diversification.