bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Impact: Wikipedia sources and edit history document two decades of the climate change field
Authors: Benjakob Omer , Jouveshomme Louise , Collet Matthieu , Augustoni Ariane , Aviram Rona 
Published: December 2023

AbstractSince being founded in 2001, Wikipedia has grown into a trusted source of knowledge online, feeding Google search results and serving as training data for ChatGPT. Understanding the accuracy of its information, the sources behind its articles and their role in the transference of knowledge to the public are becoming increasingly important questions. Meanwhile, climate change has moved to the forefront of scientific and public discourse after years of warnings from the scientific community. Therefore, to understand how it was represented on English Wikipedia, we deployed a mixed-method approach on the article for “Effects of climate change” (ECC), its edit history and references, as well as hundreds of associated articles dealing with climate change in different ways. Using automated tools to scrape data from Wikipedia, we saw new articles were created as climatology-related knowledge grew and permeated into other fields, reflecting a growing body of climate research and growing public interest. Our qualitative textual analysis shows how specific descriptions of climatic phenomena became less hypothetical, reflecting the real-world public debate. The Intergovernmental Panel on Climate Change (IPCC) had a big impact on content and structure, we found using a bibliometric analysis, and what made this possible, we also discovered through a historical analysis, was the impactful work of just a few editors. This research suggests Wikipedia’s articles documented the real-world events around climate change and its wider acceptance - initially a hypothesis that soon became a regretful reality. Overall, our findings highlight the unique role IPCC reports play in making scientific knowledge about climate change actionable to the public, and underscore Wikipedia’s ability to facilitate access to research. This work demonstrates Wikipedia can be researched using both computational and qualitative methods to better understand transference of scientific information to the public and the history of contemporary science.
Internally-consistent and fully-unbiased multimodal MRI brain template construction from UK Biobank: Oxford-MM
Authors: Arthofer Christoph , Smith Stephen M. , Douaud Gwenaëlle , Bartsch Andreas , Alfaro-Almagro Fidel , Andersson Jesper , Lange Frederik J. 
Published: December 2023

AbstractAnatomical MRI templates of the brain are essential to group-level analyses and image processing pipelines, as they provide a reference space for spatial normalisation. While it has become common for studies to acquire multimodal MRI data, many templates are still limited to one type of modality, usually either scalar or tensor-based. Aligning each modality in isolation does not take full advantage of the available complementary information, such as strong contrast between tissue types in structural images, or axonal organisation in the white matter in diffusion tensor images. Most existing strategies for multimodal template construction either do not use all modalities of interest to inform the template construction process, or do not use them in a unified framework.Here, we present multimodal, cross-sectional templates constructed from UK Biobank data: the OMM-1 template, and age-dependent templates for each year of life between 45 to 81. All templates are fully unbiased to represent the average shape of the populations they were constructed from, and internally consistent through jointly informing the template construction process with T1, T2-FLAIR and DTI data. The OMM-1 template was constructed with a multi-resolution, iterative approach using 240 individuals in the 50-55 year age range. The age-dependent templates were estimated using a Gaussian Process, which describes the change in average brain shape with age in 37,330 individuals.All templates show excellent contrast and alignment within and between modalities. The global brain shape and size is not preconditioned on existing templates, although maximal possible compatibility with MNI-152 space was maintained through rigid alignment. We showed benefits in registration accuracy across two datasets (UK Biobank and HCP), when using the OMM-1 as the template compared with FSL’s MNI-152 template, and found that the use of age-dependent templates further improved accuracy to a small but detectable extent. All templates are publicly available and can be used as a new reference space for uni- or multimodal spatial alignment.
Visual social information use in collective foraging
Authors: Mezey David , Deffner Dominik , Kurvers Ralf HJM , Romanczuk Pawel 
Published: December 2023

AbstractCollective dynamics emerge from individual-level decisions, yet we still poorly understand the link between individual-level decision-making processes and collective outcomes in realistic physical systems. Using collective foraging to study the key trade-off between personal and social information use, we present a mechanistic, spatially-explicit agent-based model that combines individual-level evidence accumulation of personal and (visual) social cues with particle-based movement. Under idealized conditions without physical constraints, our mechanistic framework reproduces findings from established probabilistic models, but explains how individual-level decision processes generate collective outcomes in a bottom-up way. In clustered environments, groups performed best if agents reacted strongly to social information, while in uniform environments, individualistic search was most beneficial. Incorporating different real-world physical and perceptual constraints profoundly shaped collective performance, and could even buffer maladaptive herding by facilitating self-organized exploration. Our study uncovers the mechanisms linking individual cognition to collective outcomes in human and animal foraging and paves the way for decentralized robotic applications.Significance statementFinding and collecting rewards in heterogeneous environments is key for adaptive collective behavior in humans, animals and machines. We present an open agent-based simulation framework to study how social information use shapes collective foraging from the bottom up. Our model combines individual evidence accumulation with spatially explicit movement. Our results connect individual-level decisions to collective dynamics in realistic physical environments, highlighting the key role of real-world constraints, thereby bringing us closer to embodied collective intelligence. Our work introduces a flexible platform to study the interplay between individual cognitive and perceptual biases, agents’ physical environment and the resulting collective dynamics and thus paves the way for fully decentralized mobile robot applications.
Single-Site Phosphorylation Elicits Structural, Dynamic, and Accessibility Changes in Proteins at both Proximal and Distal Regions to the Phosphosite
Authors: Subhadarshini Seemadri , Tandon Himani , Srinivasan Narayanaswamy , Sowdhamini Ramanathan 
Published: December 2023

ABSTRACTPhosphorylation, a fundamental cellular mechanism, intricately regulates protein function and signaling pathways. Our study employs extensive computational analyses on a curated dataset of phosphorylated and unphosphorylated protein structures to explore the multifaceted impact of phosphorylation on protein conformation. Our findings reveal that phosphorylation induces not only local changes at the phosphorylation site but also extensive alterations in distant regions, showcasing its far-reaching influence on protein structure-dynamics. Using Normal Mode Analysis (NMA), we investigate changes in protein flexibility post-phosphorylation, highlighting an enhanced level of structural dynamism. Through in-depth case studies on Polyubiquitin-B and Glycogen Synthase Kinase-3 Beta, we elucidate how phosphorylation at distinct sites leads to variable structural and dynamic modifications, potentially dictating functional outcomes. While phosphorylation largely preserves residue motion correlation, it significantly disrupts low-frequency global modes, presenting a dualistic impact on protein dynamics. We also explore alterations in the total accessible surface area (ASA), emphasizing region-specific changes around phosphorylation sites. This study sheds light on phosphorylation-induced conformational changes, dynamic modulation, and surface accessibility alterations, contributing to a comprehensive understanding of cellular regulation and suggesting promising avenues for therapeutic interventions.
Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases
Authors: Song Feizhi , Kovac Valerija , Mohammadi Behnam , Littau Lisa , Scharfenberg Franka , Angles Andreu Matamoros , Vanni Ilaria , Shafiq Mohsin , Orge Leonor , Galliciotti Giovanna , Djakkani Salma , Linsenmeier Luise , Černilec Maja , Hartman Katrina , Jung Sebastian , Tatzelt Jörg , Neumann Julia E. , Damme Markus , Tschirner Sarah K. , Lichtenthaler Stefan F. , Schmitz Matthias , Zerr Inga , Puig Berta , Tolosa Eva , Ferrer Isidro , Magnus Tim , Rupnik Marjan S. , Sepulveda-Falla Diego , Matschke Jakob , Šmid Lojze M. , Bresjanac Mara , Andreoletti Olivier , Krasemann Susanne , Foliaki Simote T. , Nonno Romolo , Becker-Pauly Christoph , Monzo Cecile , Crozet Carole , Haigh Cathryn L. , Glatzel Markus , Serbec Vladka Curin , Altmeppen Hermann C. 
Published: December 2023

AbstractProteolytic cell surface release (‘shedding’) of the prion protein (PrP), a broadly expressed GPI-anchored glycoprotein, by the metalloprotease ADAM10 impacts on neurodegenerative and other diseases in animal andin vitromodels. Recent studies employing the latter also suggest shed PrP (sPrP) to be a ligand in intercellular communication and critically involved in PrP-associated physiological tasks. Although expectedly an evolutionary conserved event, and while soluble forms of PrP are present in human tissues and body fluids, neither proteolytic PrP shedding and its cleavage site nor involvement of ADAM10 or the biological relevance of this process have been demonstrated for the human body thus far. In this study, cleavage site prediction and generation (plus detailed characterization) of sPrP-specific antibodies enabled us to identify PrP cleaved at tyrosin 226 as the physiological and strictly ADAM10-dependent shed form in humans. Using cell lines, neural stem cells and brain organoids, we show that shedding of human PrP can be stimulated by PrP-binding ligands without targeting the protease, which may open novel therapeutic perspectives. Site-specific antibodies directed against human sPrP also detect the shed form in brains of cattle, sheep and deer, hence in all most relevant species naturally affected by fatal and transmissible prion diseases. In human and animal prion diseases, but also in patients with Alzheimer’s disease, sPrP relocalizes from a physiological diffuse tissue pattern to intimately associate with extracellular aggregates of misfolded proteins characteristic for the respective pathological condition. Findings and research tools presented here will accelerate novel insight into the roles of PrP shedding (as a process) and sPrP (as a released factor) in neurodegeneration and beyond.
Adaptation to ARF6-depletion in KRAS-driven PDAC is abolished by targeting TLR2
Authors: Ghose Ritobrata , Das Shubhamay , Urgel-Solas Julia , Pezzano Fabio , Datta Debayan , Ghose Upamanyu , Zapater Antoni Ganez , Lorente Natalia Pardo , Calvo Lorena Espinar , Garcia Laura , Cannata Chiara , Ruprecht Verena , Janic Ana , Sdelci Sara 
Published: December 2023

SUMMARYMetastasis is responsible for nearly 90% of all cancer-related deaths. Despite global efforts to prevent aggressive tumours, cancers such as pancreatic ductal adenocarcinoma (PDAC) are poorly diagnosed in the primary stage, resulting in lethal metastatic disease. RAS mutations are known to promote tumour spread, with mutant KRAS present in up to 90% of cases. Until recently, mutant KRAS remained untargeted and, despite the recent development of inhibitors, results show that tumour cells develop resistance. Another strategy for targeting mutant KRAS-dependent PDAC proliferation and metastasis may come from targeting the downstream effectors of KRAS. One such axis, which controls tumour proliferation, invasiveness and immune evasion, is represented by ARF6-ASAP1. Here we show that targeting ARF6 results in adaptive rewiring that can restore proliferation and invasion potential over time. Using time-series RNA and ATAC sequencing approaches, we identified TLR-dependent NFκB, TNFα and hypoxia signalling as key drivers of adaptation in ARF6-depleted KRAS-dependent PDAC. Using in vitro and in vivo assays, we show that knocking down TLR2 with ARF6 significantly reduces proliferation, migration and invasion. Taken together, our data shed light on a novel co-targeting strategy with the therapeutic potential to counteract PDAC proliferation and metastasis.GRAPHICAL SUMMARY
Chronic metabolic stress drives developmental programs and loss of tissue functions in non-transformed liver that mirror tumor states and stratify survival
Authors: Tzouanas Constantine N. , Sherman Marc S. , Shay Jessica E.S. , Rubin Adam J. , Mead Benjamin E. , Dao Tyler T. , Butzlaff Titus , Mana Miyeko D. , Kolb Kellie E. , Walesky Chad , Pepe-Mooney Brian J. , Smith Colton J. , Prakadan Sanjay M. , Ramseier Michelle L. , Tong Evelyn Y. , Joung Julia , Chi Fangtao , McMahon-Skates Thomas , Winston Carolyn L. , Jeong Woo-Jeong , Aney Katherine J. , Chen Ethan , Nissim Sahar , Zhang Feng , Deshpande Vikram , Lauer Georg M. , Yilmaz Ömer H. , Goessling Wolfram , Shalek Alex K. 
Published: December 2023

AbstractUnder chronic stress, cells must balance competing demands between cellular survival and tissue function. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), hepatocytes cooperate with structural and immune cells to perform crucial metabolic, synthetic, and detoxification functions despite nutrient imbalances. While prior work has emphasized stress-induced drivers of cell death, the dynamic adaptations of surviving cells and their functional repercussions remain unclear. Namely, we do not know which pathways and programs define cellular responses, what regulatory factors mediate (mal)adaptations, and how this aberrant activity connects to tissue-scale dysfunction and long-term disease outcomes. Here, by applying longitudinal single-cell multi-omics to a mouse model of chronic metabolic stress and extending to human cohorts, we show that stress drives survival-linked tradeoffs and metabolic rewiring, manifesting as shifts towards development-associated states in non-transformed hepatocytes with accompanying decreases in their professional functionality. Diet-induced adaptations occur significantly prior to tumorigenesis but parallel tumorigenesis-induced phenotypes and predict worsened human cancer survival. Through the development of a multi-omic computational gene regulatory inference framework and humanin vitroand mousein vivogenetic perturbations, we validate transcriptional (RELB, SOX4) and metabolic (HMGCS2) mediators that co-regulate and couple the balance between developmental state and hepatocyte functional identity programming. Our work defines cellular features of liver adaptation to chronic stress as well as their links to long-term disease outcomes and cancer hallmarks, unifying diverse axes of cellular dysfunction around core causal mechanisms.
Understanding and exploitation of host stress responses to protein production using novel transcriptomic analytics
Authors: Rode Christoffer , Beulig Felix , Jönsson Mathias , Jahn Leonie J. , Nørholm Morten H. H. , Palsson Bernhard O. , Özdemir Emre , Yang Lei 
Published: December 2023

AbstractPredictable expression of heterologous genes in a production host is a fundamental challenge in biotechnology. While traditional methods focus on manipulating expression and the property of the heterologous gene, a systems biology approach can complement with designs to improve the host itself. Previously, Independent Component Analysis (ICA) of the RNAseq data helped reveal independently modulated gene sets (iModulons) in bacteria. This was later applied to identify common stress responses related to heterologous gene expression forEscherichia coli. In this study, we expand this analysis with additional non-enzymatic proteins and apply our findings to design novel protein production optimization. By leveraging the Precise-1K transcriptomics knowledge base, we identify three iModulons as novel transcriptional responses to protein production stress; Cold Shock, gcvB sRNA, and the uncharacterized UC-9 iModulons. By studying the gene membership in the UC-9 iModulon, we discover effective novel design targets for improving protein production. This study demonstrates the value of big data analytics and systems understanding of host responses for designing novel strategies to optimize protein production.
Fetal lung vascular development is disrupted by mechanical compression and rescued by administration of amniotic fluid stem cell extracellular vesicles via regulation of the Hippo signaling pathway
Authors: Figueira Rebeca L. , Khalaj Kasra , Antounians Lina , Doktor Fabian , Gaffi Maria Sole , Obed Mikal , Gandhi Sree , Zani Augusto 
Published: December 2023

AbstractPostnatal pulmonary hypertension is the biggest treatment challenge and major determinant for poor outcome in infants with congenital diaphragmatic hernia (CDH). CDH lungs are hypoplastic and exhibit vascular remodeling, whose pathogenesis remains poorly understood. Using a novel micro-static compression system, herein we found that mechanical compression induces vascular remodeling and downregulation of key angiogenic markers in rat and human fetal lung models, with similar features observed in CDH fetal lung autopsy samples. These fetal lung vascular changes are reversed back to normal upon administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs), a regenerative approach previously shown to restore lung branching morphogenesis and epithelial differentiation in CDH models. Exploring pathways that are dysregulated in CDH lungs and involved in mechanotransduction, we found that compressed fetal lungs had altered expression of Hippo signaling factors that was restored upon AFSC-EV administration. We found that AFSC-EV cargo contains some miRNAs involved in lung vascular development and Hippo pathway, indicating that AFSC-EV regenerative effects is associated with the delivery of specific miRNAs. This study uncovers the role of mechanical compression that herniated organs exert on CDH fetal lungs and proposes a new cell-free strategy to restore normal fetal lung vascular development.
A novel druggable DYRK3/CAMKV signaling module for Neuroblastoma tumor growth inhibition
Authors: Rozen Esteban J. , Wgglesworth Kim , Shohet Jason 
Published: December 2023

AbstractHigh-risk Neuroblastoma is a very aggressive and deadly pediatric cancer, accounting for over 15% of all childhood cancer mortality. Therefore, novel therapeutic strategies for the treatment of neuroblastoma are urgently sought for. Here, we identified the DYRK3 kinase as a critical mediator of neuroblastoma cell proliferation andin vivotumor growth. Our data suggest a role for DYRK3 as a regulator of the neuroblastoma-specific protein CAMKV, which is also required for neuroblastoma cell proliferation. We show that CAMKV is phosphorylated by DYRK3, and that inhibition of DYRK3 kinase activity induces CAMKV aggregation, probably mediated by its highly disordered C-terminal half. Importantly, we provide evidence that the DYRK3/CAMKV signaling module could play an important role in the regulation of the mitotic spindle during cell division, supporting the idea that inhibition of DYRK3 and/or CAMKV in neuroblastoma cells could constitute an innovative and highly specific intervention to fight against this dreadful pediatric cancer.
TRAIL pathway suppression of cancer cell growth and immune cell-mediated tumor cell-killing in a senescent fibroblast-constructed tumor microenvironment
Authors: Zhang Shengliang , Huntington Kelsey E. , Zhou Lanlan , Seyhan Attila A. , Kun Bianca , Carneiro Benedito A. , Kreiling Jill , Sedivy John M. , El-Deiry Wafik S. 
Published: December 2023

AbstractCellular senescence and the associated secretory phenotype (SASP) promote cancer in the aging population. During aging or upon chemotherapy exposure, cellular and molecular changes occur in non-cancerous cells and alter responses to cancer therapy, primarily via modifications in the tumor microenvironment (TME) and immune response. Targeting senescent cells through removal, modulation of the SASP, or cellular reprogramming represent promising therapeutic avenues for treating cancer. We elucidate an interplay between cancer cells, immune cells, and senescent fibroblasts and describe the impact of fibroblast senescence on tumor growth and response to cancer therapy. Cytokine profiling reveals dynamic changes in SASP production during etoposide-induced senescence in IMR90 fibroblasts. We show that SASP is partially regulated by p21 (WAF1; CDKN1A), leading to the downregulation of anti-tumorigenic cytokines and upregulation of pro-tumorigenic cytokines. Senescent fibroblasts promote bystander cancer cell growth via a p21-driven SASP. These results provide strategies to target the p21-driven SASP in the TME during cancer therapy. Treatment with TRAIL or TRAIL-inducing Dordaviprone (TIC10/ONC201) reduces cell viability of tumor cells co-cultured with senescent or proliferating fibroblasts and promotes immune-mediated tumor cell-killing in co-culture with senescent IMR90 fibroblasts. ONC201 combined with senolytic drugs (e.g., Navitoclax, Lamivudine) synergizes towards tumor suppression. These results indicate that senolytic therapies may be combined with cancer therapies to target senescence-associated changes in the TME including for modulation of the senescent cytokine landscape.
Bioorthogonal labeling enables in situ fluorescence imaging of expressed gas vesicle nanostructures
Authors: Schrunk Erik , Dutka Przemysław , Hurt Robert C. , Wu Di , Shapiro Mikhail G. 
Published: December 2023

ABSTRACTGas vesicles (GVs) are proteinaceous nanostructures that, along with virus-like particles, encapsulins, nano-cages, and other macromolecular assemblies are being developed for potential biomedical applications. To facilitate such development, it would be valuable to characterize these nanostructures’ sub-cellular assembly and localization. However, traditional fluorescent protein fusions are not tolerated by GVs’ primary constituent protein, making optical microscopy a challenge. Here, we introduce a method for fluorescently visualizing intracellular GVs using the bioorthogonal label FlAsH, which becomes fluorescent upon binding the six-amino acid tetracysteine (TC) tag. We engineered the GV subunit protein, GvpA, to display the TC tag, and showed that GVs bearing TC-tagged GvpA can be successfully assembled and fluorescently visualized in HEK 293T cells. We used fluorescence images of the tagged GVs to study GV size and distance distributions within these cells. This bioorthogonal labeling approach will enable research to provide a greater understanding of GVs and could be adapted to similar proteinaceous nanostructures.