bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecological Momentary Assessments of Trauma-Related Intrusive Memories: Potential Clinical Utility
Authors: Pollmann Yara , Clancy Kevin J. , Devignes Quentin , Ren Boyu , Kaufman Milissa , Rosso Isabelle M. 
Published: May 2024

ABSTRACTAs the global prevalence of trauma rises, there is a growing need for accessible and scalable treatments for trauma-related disorders like posttraumatic stress disorder (PTSD). Trauma-related intrusive memories (TR-IMs) are a central PTSD symptom and a target of exposure-based therapies, gold-standard treatments that are effective but resource-intensive. This study examined whether a brief ecological momentary assessment (EMA) protocol assessing the phenomenology of TR-IMs could reduce intrusion symptoms in trauma-exposed adults.Participants (N=131) experiencing at least 2 TR-IMs per week related to a DSM-5 criterion A trauma completed a 2-week EMA protocol during which they reported on TR-IM properties three times per day, and on posttraumatic stress symptoms at the end of each day. Longitudinal symptom measurements were entered into linear mixed-effects models to test the effect of Time on TR-IMs.Over the 2-week EMA protocol, intrusion symptom severity (cluster B scores) significantly declined (t = −2.78, p = 0.006), while other symptom cluster scores did not significantly change. Follow-up analyses demonstrated that this effect was specific to TR-IMs (t = −4.02, p < 0.001), and was not moderated by survey completion rate, total PTSD symptom severity, or ongoing treatment.Our findings indicate that implementing an EMA protocol assessing intrusive memories could be an effective trauma intervention. Despite study limitations like its quasi-experimental design and absence of a control group, the specificity of findings to intrusive memories argues against a mere regression to the mean. Overall, an EMA approach could provide a cost-effective and scalable treatment option targeting intrusive memory symptoms.
A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma
Authors: Pilcher William C. , Yao Lijun , Gonzalez-Kozlova Edgar , Pita-Juarez Yered , Karagkouni Dimitra , Acharya Chaitanya R. , Michaud Marina E , Hamilton Mark , Nanda Shivani , Song Yizhe , Sato Kazuhito , Wang Julia T. , Satpathy Sarthak , Ma Yuling , Schulman Jessica , D’Souza Darwin , Jayasinghe Reyka G. , Cheloni Giulia , Bakhtiari Mojtaba , Pabustan Nick , Nie Kai , Foltz Jennifer A. , Saldarriaga Isabella , Alaaeldin Rania , Lepisto Eva , Chen Rachel , Fiala Mark A. , Thomas Beena E , Cook April , Dos Santos Junia Vieira , Chiang I-ling , Figueiredo Igor , Fortier Julie , Slade Michael , Oh Stephen T. , Rettig Michael P. , Anderson Emilie , Li Ying , Dasari Surendra , Strausbauch Michael A , Simon Vernadette A ,   Immune Atlas Consortium, Rahman Adeeb H , Chen Zhihong , Lagana Alessandro , DiPersio John F. , Rosenblatt Jacalyn , Kim-Schulze Seunghee , Dhodapkar Madhav V , Lonial Sagar , Kumar Shaji , Bhasin Swati S , Kourelis Taxiarchis , Vij Ravi , Avigan David , Cho Hearn J , Mulligan George , Ding Li , Gnjatic Sacha , Vlachos Ioannis S , Bhasin Manoj 
Published: May 2024

ABSTRACTMultiple Myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We established a harmonized consortium to generate an Immune Atlas of MM aimed at informing disease etiology, risk stratification, and potential therapeutic strategies. We generated a transcriptome profile of 1,149,344 single cells from the bone marrow of 263 newly diagnosed patients enrolled in the CoMMpass study and characterized immune and hematopoietic cell populations. Associating cell abundances and gene expression with disease progression revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing patients. Furthermore, signaling analyses suggested active intercellular communication involving APRIL-BCMA, potentially promoting tumor growth and survival. Finally, we demonstrate that integrating immune cell levels with genetic information can significantly improve patient stratification.
Idecopy number variant does not influence lesion size and mortality in two C57BL/6J mouse models of cerebrovascular ischemia nor in human cerebrovascular disease. An exploratory study
Authors: Foddis Marco , Blumenau Sonja , Mueller Susanne , Messerschmidt Clemens , Rocca Clarissa , Pagnamenta Alistair T , Winek Katarzyna , Endres Matthias , Meisel Andreas , Tucci Arianna , Bras Jose , Guerreiro Rita , Beule Dieter , Dirnagl Ulrich , Sassi Celeste 
Published: May 2024

ABSTRACTContrary to the common belief, the most commonly used laboratory mouse inbred strains are shaped by a distinctive genetic and phenotypic diversity. In the past 10 years next generation sequencing unveiled a wide spectrum of genetic variants in different mouse inbred strains and the meticulous observation of researchers pointed to a variegate intra-and inter-strain phenotypic diversity. Although a genotype-phenotype correlation has been described for some traits, the relationship between several endophenotypes and causative genetic variability remains still unknown. Recently, we characterized the brain collateral plasticity in two brain ischemia C57BL/6J mouse models (i.e bilateral common carotid artery stenosis [BCCAS] and 60-min transient unilateral middle cerebral artery occlusion [MCAO]) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) plasticity. Interestingly, a copy number variant (CNV) spanningIdelocus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory. Given the critical role ofIdein vascular plasticity,IdeCNV was an excellent candidate to explain PcomA variability in C57BL/6J inbred mice. To investigate this hypothesis, we applied a combination of complementary techniques (i.e T2-weighted magnetic resonance imaging [MRI], time of flight [TOF] angiography [MRA], cerebral blood flow [CBF] imaging and histology) to characterize the collaterome in C57BL/6J BCCAS and MCAO mice and performed on these Taqman genotyping, exome sequencing, and RNA sequencing. We report anIdeCNV in a BCCAS mouse with 2 patent PcomAs. We then investigated the hypothesis thatIDEgain and loss of function mutations may have influenced the vascular phenotype in a cohort of 438,250 cases and controls (UK Biobank) and 15,790 neurological patients (Genomics England), respectively. We identified fourIDECNVs resulting in a loss of function (LoF) in one patient with hereditary ataxia, a patient with hereditary congenital heart disease and two healthy individuals. In addition, we report fourIDELoF point mutations (p.Leu5X, p.Met394ValfsX29, p.Pro14SerfsX26, p.Leu889X) present in controls or inherited from healthy parents.IdeCNV and LoF variants do not crucially influence PcomA variability in C57BL/6J inbred mice and do not cause a vascular phenotype in humans.
Heterotypic competition between cancer cells and hepatocytes generates heterogeneous context-dependent phenotypes
Authors: Spinazzola Andrea , Carvalho Tânia , Pinto Miguel Alexandre Ferreira , Marques-Reis Mariana , Gutiérrez-García Andrés , Accardi Davide , Moreno Eduardo 
Published: May 2024

AbstractCompetitive interactions between tumor cells and surrounding healthy cells are constantly present during the progression of a solid tumor, and their outcome has been proposed to affect the clinical behavior. Previous studies have described various mechanistic and molecular aspects that characterize this process, overall indicating that cancer cells behave as supercompetitors, which eliminate neighboring healthy cells to gain vital space for growth and infiltration of the tissue. Nevertheless, there is a lack of systematic characterization of these competitive interactions, particularly in the context of cancer in mammals. Furthermore, previous studies in the field of cell competition have primarily focused on homotypic cell competition, involving different clones of the same cell or cells deriving from the same tissue. Data are scarce regarding heterotypic cell competition between two unrelated cell types, which is particularly critical for the understanding of metastatic tumors. In this research, we study cell competition in the context of liver metastases, providing a broad characterization of this process in different relevant scenarios, including cells growingin vitroin 2D and 3D, andin vivo. Results show thatin vitro, only a subset of cancer cell lines are coherently strong or moderate competitors against hepatocytes, while the remaining demonstrate poor competitiveness. The competitive proficiency can vary depending on the experimental growth system that is employed, and often predicts the phenotype of liver metastases in terms of aggressiveness and morphology. Finally, our data point towards an involvement of mechanical competition in determining the supercompetitor trait of cancer cells. Altogether, our research provides the first comprehensive characterization of heterotypic cell competition, and indicates that cancer cells possess heterogeneous competitive proficiency towards hepatocytes which can be affected by the growth conditions.
MetaDAG: a web tool to generate and analyse metabolic networks
Authors: Palmer-Rodríguez Pere , Alberich Ricardo , Reyes-Prieto Mariana , Castro José A. , Llabrés Mercè 
Published: May 2024

AbstractWe introduce MetaDAG, a web-based tool designed for metabolic network reconstruction and analysis. MetaDAG is capable of constructing metabolic networks associated with specific organisms, sets of organisms, sets of reactions, sets of enzymes, and sets of KO (KEGG Orthology) identifiers. To generate these metabolic networks, MetaDAG retrieves from the KEGG database the chemical reaction information that corresponds to the user’s queries. MetaDAG computes a reaction graph as a first metabolic graph model. This reaction graph is a network in which nodes represent reactions, and edges between reactions indicate the presence of a metabolite produced by one reaction and consumed by another. Next, as a second metabolic model, MetaDAG computes a directed acyclic graph called a metabolic DAG (m-DAG for short). The m-DAG is obtained from the reaction graph by collapsing all strongly connected components into single nodes. As a result, the m-DAG representation reduces considerably the number of nodes while keeping and also highlighting the network’s connectivity. Both metabolic models, the reaction graph, and the m-DAGs, are displayed on an interactive web page to assist the users in visualising and analysing the networks. Furthermore, users can retrieve the node’s information linked to the KEGG database. All generated files, including images containing metabolic network information and analysis results, are available for download directly from the web page. In the Eukariotes test presented here, MetaDAG has demonstrated its effectiveness in classifying all eukaryotes from the KEGG database at both the kingdom and phyla taxonomy levels.
Rhythmidia: a modern tool for circadian period analysis of filamentous fungi
Authors: Keeley Alex T. , Lotthammer Jeffrey M. , Pelham Jacqueline F. 
Published: May 2024

AbstractCircadian rhythms are ubiquitous across the kingdoms of life and serve important roles in regulating physiology and behavior at many levels. These rhythms occur in ∼24-hour cycles and are driven by a core molecular oscillator. Circadian timekeeping enables organisms to anticipate daily changes by timing their growth and internal processes.Neurospora crassais a model organism with a long history in circadian biology, having conserved eukaryotic clock properties and observable circadian phenotypes. A core approach for measuring circadian function in Neurospora is to follow daily oscillations in the direction of growth and spore formation along a thin glass tube (race tube). While leveraging robust phenotypic readouts is useful, interpreting the outputs of large-scale race tube experiments by hand can be time-consuming and prone to human error. To provide the field with an efficient tool for analyzing race tubes, we present Rhythmidia, a graphical user interface (GUI) tool written in Python for calculating circadian periods and growth rates of Neurospora. Rhythmidia is open source, has been benchmarked against the current state-of-the-art, and is easily accessible on GitHub.
TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in Triple-Negative Breast Cancer
Authors: Sim Nicholas , Carter Jean-Michel , Deka Kamalakshi , Tan Benita Kiat Tee , Sim Yirong , Tan Suet-Mien , Li Yinghui 
Published: May 2024

AbstractTriple Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype suffering from limited targeted treatment options. Following recent reports correlating Fn14 receptor overexpression in ER-negative breast cancers with metastatic events, we show that Fn14 is specifically overexpressed in TNBC patients and associated with poor survival. We demonstrate that constitutive Fn14 signalling rewires the transcriptomic and epigenomic landscape of TNBC, leading to enhanced tumour growth and metastasis. We further illustrate that such mechanisms activate TNBC-specific super enhancers (SE) to drive the transcriptional activation of cancer dependency genes via chromatin looping. In particular, we uncover the SE-driven upregulation of NAMPT, which promotes NAD+ and ATP metabolic reprogramming critical for filopodia formation and metastasis. Collectively, our study details the complex mechanistic link between TWEAK/Fn14 signalling and TNBC metastasis, which reveals several vulnerabilities which could be pursued for the targeted treatment of TNBC patients.
In Search of the Perfect Model: How Cancer Cell Lines Relate to Native Cancers
Authors: Paloots Rahel , Yang Ziying , Baudis Michael 
Published: May 2024

Cancer cell lines are frequently used in biological and translational research to study cellular mechanisms and explore treatment options. However, cancer cell lines may display mutational profiles divergent from native cancers or may be misidentified or contaminated. We explored how similar cancer cell lines are to native cancers to find the most suitable representations for the corresponding diseases by utilising large collections of copy number variation (CNV) profiles and applied machine learning (ML) algorithms to predict cell line classifications.Our results confirm that cancer cell lines indeed accumulate more mutations compared to native cancers but retain similar CNV profiles. We demonstrate that many relevant oncogenes and tumor suppressor genes are altered by CNV events in both cancers and their corresponding cell lines. Based on the similarities between the two groups and the predictions of the ML model, we provide some recommendations about cell lines with good potential to represent selected cancer types inin vitrostudies.
Functional benefits of continuous vs. categorical listening strategies on the neural encoding and perception of noise-degraded speech
Authors: Rizzi Rose , Bidelman Gavin M. 
Published: May 2024

AbstractAcoustic information in speech changes continuously, yet listeners form discrete perceptual categories to ease the demands of perception. Being a more continuous/gradient as opposed to a discrete/categorical listener may be further advantageous for understanding speech in noise by increasing perceptual flexibility and resolving ambiguity. The degree to which a listener’s responses to a continuum of speech sounds are categorical versus continuous can be quantified using visual analog scaling (VAS) during speech labeling tasks. Here, we recorded event-related brain potentials (ERPs) to vowels along an acoustic-phonetic continuum (/u/ to /a/) while listeners categorized phonemes in both clean and noise conditions. Behavior was assessed using standard two alternative forced choice (2AFC) and VAS paradigms to evaluate categorization under task structures that promote discrete (2AFC) vs. continuous (VAS) hearing, respectively. Behaviorally, identification curves were steeper under 2AFC vs. VAS categorization but were relatively immune to noise, suggesting robust access to abstract, phonetic categories even under signal degradation. Behavioral slopes were positively correlated with listeners’ QuickSIN scores, suggesting a behavioral advantage for speech in noise comprehension conferred by gradient listening strategy. At the neural level, electrode level data revealed P2 peak amplitudes of the ERPs were modulated by task and noise; responses were larger under VAS vs. 2AFC categorization and showed larger noise-related delay in latency in the VAS vs. 2AFC condition. More gradient responders also had smaller shifts in ERP latency with noise, suggesting their neural encoding of speech was more resilient to noise degradation. Interestingly, source-resolved ERPs showed that more gradient listening was also correlated with stronger neural responses in left superior temporal gyrus. Our results demonstrate that listening strategy (i.e., being a discrete vs. continuous listener) modulates the categorical organization of speech and behavioral success, with continuous/gradient listening being more advantageous to speech in noise perception.
Long-term stability of dominance hierarchies in a wild parrot with fission-fusion dynamics
Authors: Penndorf Julia , Farine Damien , Martin John , Aplin Lucy 
Published: May 2024

AbstractDominance hierarchies allow animals living in stable groups to limit the costs of fighting over access to resources. However, little is known about whether hierarchies are maintained in more open, fission-fusion societies, where individuals interact with large numbers of individuals. We recorded social associations and aggressive interactions in a highly social, communally roosting parrot, the sulphur-crested cockatoo (Cacatua galerita). By following 515 individuals across three neighbouring roosts and recording social interactions during foraging, we show that sulphur-crested cockatoos form clear linear hierarchies. Hierarchies are primarily roost based, but also incorporate birds from outside the roost. We find that an individual’s dominance rank is affected by sex and age, with males ranking higher than females and adults ranking higher than juveniles. Finally, we find despite highly dynamic social associations (fission-fusion dynamics) among individuals, hierarchies are stable, with dominance ranks being highly repeatable across years. This study demonstrates that stable and/or closed group membership are not pre-requisites for dominance hierarchies to emerge.
FlyBox: A Flexible Open-Source Behavior Monitoring System
Authors: Le Jasmine Quynh , Yu Albert D. , Dai Xihuimin , Allum Christopher , Bradley Olivia Jo , McAneney Sophia , Schwarzinger Florian , Sherman Zachary , Alvarez Jose E. , Berglund Gillian , Shin Daniel , Keefer Evelyn , Neeley Lawrence , Rosbash Michael 
Published: May 2024

AbstractOver the past two decades, the vast majority of circadian behavior inDrosophilahas been recorded in Drosophila Activity Monitor (DAM) boards. Though simple and robust, locomotor behavior recording via DAM boards can be prohibitively expensive, especially when taking incubator costs into consideration. Furthermore, their simplicity limits their experimental options and resolution. Here, we present the FlyBox: a simple, open-source benchtop locomotor activity recording system. FlyBox was designed to monitor activity in animals loaded into a standard laboratory multi-well plate. It features light-tight construction and multiple programmable LEDs for simulating day/night cycles and optogenetic manipulation. In total, a single FlyBox costs approximately $750 to build and around two days of labor. In addition, we also present the FlyBoxScanner software to simplify activity monitoring while maintaining compatibility with DAM analysis software. FlyBox is an attractive and affordable package for behavior monitoring that also offers considerable room for customization. Materials and instructions for the FlyBox are available athttps://github.com/Rosbash-Lab-FlyBox/FlyBox, and FlyBoxScanner is available athttps://github.com/jose-elias-alvarez/flybox-scanner.
Streptolysin O Accelerates the Conversion of Plasminogen to Plasmin
Authors: Tang Di , Khakzad Hamed , Hjortswang Elisabeth , Malmström Lars , Ekström Simon , Happonen Lotta , Malmström Johan 
Published: May 2024

AbstractStreptococcus pyogenesis a human-specific bacterial pathogen that produces several proteins that exploit the plasminogen (PLG)-plasmin (PLM) fibrinolysis system to dismantle blood clots and to facilitate spread and survival within the host. In this study, we explored the interactions between streptolysin O (SLO), a key cytolytic toxin produced byS. pyogenes, and human plasma proteins using affinity-enrichment mass spectrometry. SLO binds specifically to PLG, and this interaction accelerates the conversion of PLG to PLM by tissue-type plasminogen activator (tPA). To further investigate the molecular detail of the PLG-SLO interaction, we employed hydrogen/deuterium exchange mass spectrometry combined with targeted cross-linking mass spectrometry, uncovering that SLO binding induces local conformational shifts in PLG. These changes lead to the formation of a stabilized intermediate PLG-SLO complex that becomes significantly more sensitive to proteolytic processing by tPA. Our findings reveal a conserved moonlighting pathomechanistic role for SLO extending beyond the well characterized cytolytic activity. Additionally, the work underscores the diversity of functional proteomics in identifying and clarifying new host-pathogen interactions.