bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruptive changes in tissue microenvironment prime oncogenic processes at different stages of carcinogenesis in lung
Authors: Venkat Vignesh , Hu Xiaoju , Biswas Antara , Saxena Ankit , Malhotra Jyoti , Reidlinger Gregory , De Subhajyoti 
Published: November 2024

AbstractCarcinogenesis is characterized not only by the uncontrolled growth of malignant cells but also by the disruption of the normal balance of cellular processes and intercellular interactions in the microenvironment that overcome the constraints of tissue homeostasis and support malignant growth. We profiled benign pulmonary dysplasia, carcinoma in situ, and invasive lung carcinomas at single-cell resolution to identify composite changes in cellular processes, signaling, and interactions among tumor-immune-stromal cells in the microenvironment in progressively advanced disease stages. We developed OncoTerrain, a hyperparameter-tuned model that captured synergistic multimodal signatures of an increasingly perturbed microenvironment in malignant disease stages and identified composite microenvironmental changes that supported cancer hallmarks. Key cancer-related changes in transcriptional states, cellular processes, and intercellular interactions involving immune, fibroblast, and stromal cell types preceded tumor initiation and were often synergistic. The microenvironment of increasingly malignant tissues was characterized by immune avoidance, ECM remodeling, and altered cell mobility. There were changes in cell states in fibroblasts, macrophages, and their inter-cellular interactions with other cell types, whereas T-cell activation occurred late. The in-situ carcinomas showed variations in the composite microenvironmental states that corroborated their pathology, which was not apparent at the genome level. A subset of those harbored populations of tumor and non-tumor cells with aggressive characteristics in some but not all aspects of hallmarks of carcinogenesis in the lung. We suspect that the variation in the coordination of microenvironmental cues may influence why some but not all in-situ tumors progress to the advanced stages.
iModMix: Integrative Module Analysis for Multi-omics Data
Authors: Narváez-Bandera Isis , Lui Ashley , Mekonnen Yonatan Ayalew , Rubio Vanessa , Sulman Noah , Wilson Christopher , Ackerman Hayley D. , Ospina Oscar E. , Gonzalez-Calderon Guillermo , Flores Elsa , Li Qian , Chen Ann , Fridley Brooke , Stewart Paul 
Published: November 2024

AbstractSummaryThe integration of metabolomics with other omics (“multi-omics”) offers complementary insights into disease biology. However, this integration remains challenging due to the fragmented landscape of current methodologies, which often require programming experience or bioinformatics expertise. Moreover, existing approaches are limited in their ability to accommodate unidentified metabolites, resulting in the exclusion of a significant portion of data from untargeted metabolomics experiments. Here, we introduceiModMix - Integrative Module Analysis for Multi-omics Data, a novel approach that uses a graphical lasso to construct network modules for integration and analysis of multi-omics data.iModMixuses a horizontal integration strategy, allowing metabolomics data to be analyzed alongside proteomics or transcriptomics to explore complex molecular associations within biological systems. Importantly, it can incorporate both identified and unidentified metabolites, addressing a key limitation of existing methodologies.iModMixis available as a user-friendly R Shiny application that requires no programming experience (https://imodmix.moffitt.org), and it includes example data from several publicly available multi-omic studies for exploration. An R package is available for advanced users (https://github.com/biodatalab/iModMix).Availability and implementationShiny application:https://imodmix.moffitt.org. The R package and source code:https://github.com/biodatalab/iModMix.
Capacity building needed to reap the benefits of access to biodiversity collections
Authors: Groom Quentin , Meeus Sofie , Barrios Sara , Childs Catherine , Clubbe Colin , Corbett Ernestine , Francis Sarita , Gray Alan , Harding Luke , Jackman Annick , Machin Rebecca , McGovern Andrew , Pienkowski Mike , Ryan Delmaude , Sealys Chris , Wensink Catherine , Peyton Jodey 
Published: November 2024

SummaryThis research examines biodiversity specimens from two areas of the Caribbean to understand patterns of collection and the roles of the people involved. Using open data from the Global Biodiversity Information Facility (GBIF) and Wikidata, we aimed to uncover geographic and historical trends in specimen use. This study aims to provide concrete evidence to guide collaboration between collection-holding institutions and the communities that need their resources most.We analysed biodiversity specimens from Montserrat and the Cayman Islands in three steps. First, we extracted specimen data from GBIF, disambiguated collector names, and linked them to unique biographical entries. Next, we connected collectors to their publications and specimens. Finally, we analysed the modern use of these specimens through citation data, mapping author affiliations and research themes.Specimens are predominantly housed in the Global North and were initially used by their collectors, whose focus was largely on taxonomy and biogeography. With digitisation, use of these collections remains concentrated in the Global North and covers a broader range of subjects, although Brazil and China stand out as significant users of digital collection data compared to other similar countries.The availability of open digital data from collections in the Global North has led to a substantial increase in the reuse of these data across biodiversity science. Nonetheless, most research using these data is still conducted in the Global North. For the non-monetary benefits of digitisation to extend to the countries of origin, capacity building in the Global South is crucial, Open Data alone are insufficient.Societal Impact StatementDigital biodiversity data from herbaria and museums hold significant potential for nature conservation in the Global South, yet many regions, like Montserrat and the Cayman Islands in the Caribbean, are, for multiple reasons, unable to fully leverage this information. This lack of skills and resources limits local conservation efforts, showing the need for more investment in training, facilities, and expertise. Although past funding has helped improve coordination and build skills, our findings show that more work is needed to make sure conservation in these biodiverse areas can continue in the long term.
TopLib: Building and searching top-down mass spectral libraries for proteoform identification
Authors: Li Kun , Tang Haixu , Liu Xiaowen 
Published: November 2024

AbstractMass spectral library search is a widely used approach for spectral identification in mass spectrometry (MS)-based proteomics. While numerous methods exist for building and searching bottom-up mass spectral libraries, there is a lack of software tools for top-down mass spectral libraries. To fill the gap, we introduce TopLib, the first software package designed for building and searching top-down spectral libraries. TopLib utilizes an efficient spectral representation technique to reduce database size and improve query speed and performance. We systematically evaluated various spectral representation techniques and scoring functions for top-down spectral clustering and search. Our results demonstrated that TopLib is 140 times faster and achieves better reproducibility in proteoform identification compared with conventional database search methods in top-down MS.
Midbrain dopamine D2R regulates the salience of threat-related events
Authors: Castell Laia , Rogliardo Angelina , Borgne Tinaig Le , Naon Claire , Cathala Adeline , Puighermanal Emma , Makrini Leila , Mashhour Nejmeh , Petit Chloé P. , Bernat Claire , Nouvian Régis , Cutando Laura , Revest Jean-Michel , Faure Philippe , Besnard Antoine , Bellone Camilla , Monteil Arnaud , Gangarossa Giuseppe , Marti Fabio , Valjent Emmanuel 
Published: November 2024

SummarySalience attributed to stimuli predicting rewarding or aversive outcomes is critical for adaptive behavior. Dopamine (DA)-neurons play a central role in this process by modulating responses to both rewarding and aversive cues. DA-neurons are tightly and readily modulated by DA D2 autoreceptors (autoD2Rs), but their role in regulating responses to aversive stimuli remains unclear. In this study, we investigated the role of autoD2R in regulating the activity of VTA DA-neurons in response to salient aversive stimuli. UsingDrd2Slc6a3mice, in whichDrd2is selectively deleted in DA-neurons, we observed enhanced excitatory and inhibitory responses of VTA DA-neurons to aversive stimuli, suggesting that autoD2R acts as a critical regulatory brake. Importantly, this modulation occurred independently of either the pacemaker activity of DA-neurons or their coupling to the non-selective sodium leak channel NALCN. Behaviorally,Drd2Slc6a3male mice showed enhanced discrimination between threat-predicting and non-predicting cues that persisted during extinction learning, highlighting a sex-biased role of autoD2R in threat processing. Our results provide new mechanistic insights through which autoD2R influence behavioral responses to aversive stimuli, with implications for understanding neuropsychiatric disorders characterized by maladaptive threat processing.
LTB4is converted into a potent human neutrophil NADPH oxidase activator via a receptor transactivation mechanism in which the BLT1receptor activates the free fatty acid receptor 2
Authors: Wu Yanling , Dahlgren Claes , Forsman Huamei , Sundqvist Martina 
Published: November 2024

AbstractThe endogenous neutrophil chemoattractant leukotriene B4(LTB4) is a biased signalling agonist that potently increases the intracellular concentration of free calcium ions ([Ca2+]i), but alone is a weak activator of the neutrophil superoxide anion (O2-)-generating NADPH oxidase. However, in this study we show that an allosteric modulator of the free fatty acid 2 receptor (FFA2R) converts LTB4into a potent NADPH oxidase activating agonist. While an allosteric modulation of FFA2R was required for LTB4receptor 1 (BLT1R)-mediated activation of the NADPH oxidase, the LTB4-induced increase in [Ca2+]iwas not affected by the modulator. Thus, the biased BLT1R signalling pattern was altered in the presence of the allosteric FFA2R modulator, being biased with a preference towards the signals that activate the NADPH oxidase relative to an increase in [Ca2+]i. Both BLT1R and FFA2R belong to the family of G protein-coupled receptors (GPCRs), and our results show that a communication between the activated BLT1R and the allosterically modulated FFA2Rs generates signals that induce NADPH oxidase activity. This is consistent with a previously described receptor transactivation (crosstalk) model whereby the function of one neutrophil GPCR can be regulated by receptor downstream signals generated by another GPCR. Furthermore, the finding that an allosteric FFA2R modulator sensitises not only the response induced by orthosteric FFA2R agonists but also the response induced by LTB4, violates the receptor restriction properties that normally define the selectivity of allosteric GPCR modulators.
AIP56, an AB toxin secreted byPhotobacterium damselaesubsp.piscicida, has tropism for myeloid cells
Authors: Freitas Inês Lua , Macedo Fátima , Oliveira Liliana , Oliveria Pedro , do Vale Ana , dos Santos Nuno M.S. 
Published: November 2024

AbstractThe AB-type toxin AIP56 is a key virulence factor ofPhotobacterium damselaesubsp.piscicida(Phdp), inducing apoptosis in fish immune cells. The discovery of AIP56-like and AIP56-related toxins in diverse organisms, including human-associatedVibriostrains, highlights the evolutionary conservation of this toxin family, suggesting that AIP56 and its homologs may share conserved receptors across species. These toxins have potential for biotechnological applications, such as therapeutic protein delivery and immune modulation. Herein, the cell specificity of AIP56 for immune cells in sea bass, mice, and humans was characterized. Whether AIP56 interacts directly or indirectly with sea bass neutrophils was never investigated and it was shown that only a small population of sea bass neutrophils internalized AIP56, indicating that most of the neutrophilic destruction duringPhdpinfection and/or AIP56 intoxication does not result from the direct toxicity of the toxin. Moreover, the cellular tropism of AIP56 for myeloid cells was observed in the three species, including its preference for macrophages. Further, mouse and human M0 and M2-like macrophages internalized more toxin than M1-like macrophages. Despite the limited interaction of lymphoid cells with AIP56, mouse B1-cells were able to internalize the toxin, possibly due to its myeloid features. These findings are relevant for both pathogenicity and biomedical contexts.
Single-cell analyses reveal that monocyte gene expression profiles influence HIV-1 reservoir size in acutely treated cohorts
Authors: Ehrenberg Philip K. , Geretz Aviva , Volcic Meta , Izumi Taisuke , Yum Lauren , Waickman Adam , Shangguan Shida , Paquin-Proulx Dominic , Creegan Matthew , Bose Meera , Machmach Kawthar , McGraw Aidan , Narahari Akshara , Currier Jeffrey R. , Sacdalan Carlo , Phanuphak Nittaya , Apps Richard , Corley Michael , Ndhlovu Lishomwa C. , Slike Bonnie , Krebs Shelly J. , Anonworanich Jintanat , Tovanabutra Sodsai , Robb Merlin L. , Eller Michael A. , Laird Gregory M. , Cyktor Joshua , Daar Eric S. , Crowell Trevor A. , Mellors John W. , Vasan Sandhya , Michael Nelson L. , Kirchhoff Frank , Thomas Rasmi 
Published: November 2024

ABSTRACTElimination of latent HIV-1 is a major goal of AIDS research but the host factors determining the size of these reservoirs are poorly understood. Here, we investigated whether differences in host gene expression modulate the size of the HIV-1 reservoir during suppressive ART. Peripheral blood mononuclear cells (PBMC) from fourteen individuals initiating ART during acute infection who demonstrated effective viral suppression but varying magnitude of total HIV-1 DNA were characterized by single-cell RNA sequencing (scRNA-seq). Differentially expressed genes and enriched pathways demonstrated increased monocyte activity in participants with undetectable HIV-1 reservoirs.IL1Bexpression in CD14+ monocytes showed the greatest fold difference. The inverse association ofIL1Bwith reservoir size was validated in an independent cohort comprised of 38 participants with different genetic backgrounds and HIV-1 subtype infections, and further confirmed with intact proviral DNA assay (IPDA®) measurements of intact HIV-1 proviruses in a subset of the samples. Modeling interactions with cell population frequencies showed that monocyteIL1Bexpression associated inversely with reservoir size in the context of higher frequencies of central memory CD4+ T cells, implicating an indirect effect ofIL1Bvia the cell type well established to be a reservoir for persistent HIV-1. Signatures consisting of co-expressed genes includingIL1Bwere highly enriched in the “TNFα signaling via NF-κB” geneset. Functional analyses in cell culture revealed that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART treated individuals. Altogether, unbiased high throughput scRNA-seq analyses revealed that monocyteIL1Bvariation could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.
SNR-Efficient Whole-Brain Pseudo-Continuous Arterial Spin Labeling Perfusion Imaging at 7 Tesla
Authors: Woods Joseph G. , Ji Yang , Li Hongwei , Hess Aaron , Okell Thomas W. 
Published: November 2024

AbstractPurposeTo optimize pseudo-continuous arterial spin labeling (PCASL) parameters to maximize SNR efficiency for RF power constrained whole brain perfusion imaging at 7 T.MethodsWe used Bloch simulations of pulsatile laminar flow to optimize the PCASL parameters for maximum SNR efficiency, balancing labeling efficiency and total RF power. The optimization included adjusting the inter-RF pulse spacing (TRPCASL), mean B1+(B1 ave), slice-selective gradient amplitude (Gmax), and mean gradient amplitude (Gave). In vivo data were acquired from four volunteers at 7 T to validate the optimized parameters. Dynamic B0-shimming and flip angle adjustments were utilized to avoid needing to make the PCASL parameters robust to B0/B1+variations.ResultsThe optimized PCASL parameters achieved a significant (3.1x) reduction in RF power while maintaining high labeling efficiency. This allowed for longer label durations and minimized deadtime, and resulted in a 126% improvement in SNR efficiency in vivo compared to a previously proposed protocol. Additionally, the static tissue response was improved, reducing the required distance between labeling plane and imaging volume.ConclusionThese optimized PCASL parameters provide a robust and efficient approach for whole brain perfusion imaging at 7 T, with significant improvements in SNR efficiency and reduced SAR burden.
Wound state monitoring by multiplexed, electrochemical, real-time, localized, inflammation-tracking nitric oxide sensor (MERLIN)
Authors: Wang Liyang , Wang Yingqiao , Bartlett Mabel , San Roman Daniel , Balakrishnan Gaurav , Gershanok Samuel , Khan Reem , Skillen Clint , Butler Shanae , Kulkarni Mangesh , Cohen-Karni Devora , Brown Bryan , Cohen-Karni Tzahi 
Published: November 2024

AbstractNitric oxide (NO) released endogenously by induced nitric oxide synthase (iNOS) in macrophages is a key regulatory biomarker for wound inflammation. Detecting NO directly on the wound bed is challenging due to its short half-life time (6 – 50 s), low physiological concentration (nM - µM) and interferences in the complex wound environment. Existing NO sensors suffer from limitations such as rigid substrates, single point of detection and complex measurement setup. Here we present a compliant, multiplexed, electrochemical, real-time, localized, inflammation-tracking nitric oxide sensor (MERLIN) array for in vivo spatiotemporal measurement of NO, with high sensitivity (15.6 ± 5.0 nA/μM for 1.5 mm diameter electrodes), selectivity against nitrites (ca. 27900-fold), ascorbic acid (ca. 3800-fold), and uric acid (ca. 6900-fold), and low limit of detection (8.00 nM). We developed a robust device fabrication protocol, comprehensive and highly reproducible in vitro characterization yielding a consistent device performance deployed for wound healing diagnostics. MERLIN spatiotemporally tracked NO on rat skin wounds for 7 days and results indicated that NO peaks on day 3, in line with previously reported iNOS activity. MERLIN allows spatial mapping of the NO gradient across the wound bed, which can be used to provide diagnostic information to assist wound care.
Attention-dependent attribute comparisons underlie multi-attribute decision-making in orbitofrontal cortex
Authors: Perkins Aster Q. , Rich Erin L. 
Published: November 2024

AbstractEconomic decisions often require weighing multiple dimensions, or attributes. The orbitofrontal cortex FC) is thought to be important for computing the integrated value of an option from its attributes and comparing lues to make a choice. Although OFC neurons are known to encode integrated values, evidence for value mparison has been limited. Here, we used a multi-attribute choice task for monkeys to investigate how OFC eurons integrate and compare multi-attribute options. Attributes were represented separately and eye tracking as used to measure attention. We found that OFC neurons encode the value of attended attributes, dependent of other attributes in the same option. Encoding was negatively weighted by the value of the same tribute in the other option, consistent with a comparison between the two like attributes. These results indicate at OFC computes comparisons among attributes rather than integrated values, and does so dynamically, ifting with the focus of attention.
scTrace+: enhance the cell fate inference by integrating the lineage-tracing and multi-faceted transcriptomic similarity information
Authors: Guo Wenbo , Chen Zeyu , Li Xinqi , Huang Jingmin , Hu Qifan , Gu Jin 
Published: November 2024

AbstractDeciphering the cell state dynamics is crucial for understanding biological processes. Single-cell lineage tracing technologies provide an effective way to track the single-cell lineages by heritable DNA barcodes, but the high missing rates of lineage barcodes and the intra-clonal heterogeneity bring great challenges for dissecting the mechanisms of cell fate decision. Here, we systematically evaluate the feature of single-cell lineage tracing data, and then develop an algorithm scTrace+ to enhance the cell dynamic traces by incorporating multi-faceted transcriptomic similarities into lineage relationships via a Kernelized Probabilistic Matrix Factorization model. We assess its feasibility and performance by conducting ablation and benchmarking experiments on multiple real datasets, and show scTrace+ can accurately predict the fates of cells. Further, scTrace+ effectively identifies some important driver genes implicated in cellular fate decision of diverse biological processes, such as the cell differentiation or the tumor drug responses.
No Effect of Value on the Task Irrelevant Auditory Mismatch Negativity
Authors: Hutchinson Brendan T. , Jack Bradley N. , Budd Alycia , Calabro Ryan , Fogarty Danielle , Nicholls Michael E.R. , Griffiths Oren 
Published: November 2024

AbstractBehavioural and neuroscientific evidence suggests visual stimuli that signal value involuntarily capture attention and are preferentially processed, even when unattended. We examined whether learned value associations for task-irrelevant auditory stimuli modulate pre-attentive processing and involuntarily capture attention. Across two experiments, the effect of learned value on the visual- and auditory-evoked mismatch negativity (MMN) and P3a event-related potential (ERP) components was measured. Participants performed a primary visual detection task while an irrelevant, unattended oddball stimulus stream was concurrently presented. Deviants within this oddball stream had been previously learned to signal one of several value outcomes: monetary reward, loss or no change. Neither the auditory nor the visual MMN was influenced by these value associations. However, stimulus value affected performance on the primary task and the magnitude of the P3a in those who could identify the stimulus-value pairings at test. Supplementary mass univariate analyses and time frequency decomposition (theta phase-locking) confirmed the presence of the MMN and the absence of any influence of stimulus value on the MMN response. Findings suggest that learned value associations do not meaningfully influence the MMN prediction signaling mechanism for task-irrelevant auditory stimuli.