bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrochemical Biosensor Using Polymer Nanocomposites for G6PD Deficiency Detection
Authors: Salas Ronald Rastre , Paula Marcos Marques da Silva , Romaguera Barcelay Yonny , Brito Walter Ricardo 
Published: March 2024

ABSTRACTElectrochemical biosensors based on the combination of DHP, OG, AuNPs, and G6PD, used to determine the enzymatic activity of G6PD, showed optimal current intensity values close to pH 7.8 at room temperature. Square wave voltammetry was optimized and used to evaluate the responses of the biosensors during the enzymatic reaction and construct the analytical curves. The best results were found under the following conditions: 30 minutes of incubation, in the range of NAD+concentrations from 0.75 to 6 μmol L−1; obtaining coefficient of determination (R2) values between 98 and 99% about the analytical curves. The biosensors maintained their stability after five days of storage. The calculated LOD and LOQ limits showed good sensitivity of the method, achieving results in the order of 10-6mol L−1.
Rare Copy Number Variant analysis in case-control studies using SNP Array Data: a scalable and automated data analysis pipeline
Authors: Artaza Haydee , Lavrichenko Ksenia , Wolff Anette S.B. , Røyrvik Ellen C. , Vaudel Marc , Johansson Stefan 
Published: March 2024

AbstractBackgroundRare copy number variants (CNVs) significantly influence the human genome and may contribute to disease susceptibility. High-throughput SNP genotyping platforms provide data that can be used for CNV detection, but it requires the complex pipelining of bioinformatic tools. Here, we propose a flexible bioinformatic pipeline for rare CNV analysis from human SNP array data.ResultsThe pipeline performs two major tasks: (1) CNV detection and quality control, and (2) rare CNV analysis. It is implemented in Snakemake following a rule-based structure that enables automation and scalability while maintaining flexibility.ConclusionsOur pipeline automates the detection and analysis of rare CNVs. It implements a rigorous CNV quality control, assesses the frequencies of these rare CNVs in patients versus controls, and evaluates the impact of CNVs on specific genes or pathways. We hence aim to provide an efficient yet flexible bioinformatic framework to investigate rare CNVs in biomedical research.
The molecular basis of pine wilt disease resistance inPinus massoniana
Authors: Wang Jinjin , Cai Shouping , Zeng Liqiong , Tong Jie , Hang Danling , Zhang Xinliang , Fang Yu , Su Shunde , Su Jun 
Published: March 2024

AbstractPine wilt disease (PWD), caused by the pine wood nematode (PWN)Bursaphelenchus xylophilus, results in significant economic and ecological damage toPinusforests and plantations worldwide.Pinus massonianais the primary host of PWD in southern China, but its response to the PWN remains largely unstudied. Previously, we observed PWD in aP. massoniananursery that contained over 71 commonly used cultivars. Through field phenotyping, we identified two groups of PWN resistant cultivars. Resistant cultivars (RC) exhibited very low PWN carrying amounts (PCA) and had relatively low mortality, and tolerant cultivars (TC) had high PCA but low mortality. In this study, we confirmed via PWN inoculation assays that the resistant and tolerant cultivars had lower mortality rates, 10% and 11%, respectively, than other cultivars (which had a mortality rate of 83.3%). The RC had a PCA that was significantly lower than that of other cultivars, while the TC exhibited a higher PCA. To explore the molecular mechanisms underlying the response ofP. massonianato PWN, the transcriptome and metabolome of the above cultivars were profiled by high throughput sequencing. As no reference genome is available forP. massoniana, we generated a new full-length transcriptome library with iso-seq. Using the transcriptome and metabolome from differentP. massonianacultivars inoculated with PWN, we found three major PWD resistance strategies. 1) The common response strategy involved three important molecular pathways. First, synthesis of indole-3-acetic acid (IAA) and abcisic acid (ABA) were suppressed during PWN invasion, thus suppressing the synthesis of polysaccharides (especially myo-inositol and trehalose) and (-)-riboflavin through ABC transporters. Second, by inhibiting aspartic acid, the synthesis of arginine and proline through APS5 (aspartate aminotransferase 5) were suppressed. Third, by reducing cysteine, GERD (germacrene D synthase) was up-regulated, and sesquiterpenoid and triterpenoid metabolites were accumulated to resist PWN invasion. 2) The most effective resistance strategy involved the accumulation of reactive oxygen species (ROS), which enhanced jasmonic acid (JA) accumulation and highly induced the expression of chitinase, thus improving resistance to PWN. 3) The tolerance strategy involved the induction of phosphatidylcholine, which promoted flavonoid and anthocyanin synthesis via LPIN (phosphatidate phosphatase), LOX2S (lipoxygenase), and LOX1_5 (linoleate 9S-lipoxygenase), thus significantly inhibiting the pathogenicity of the PWN but not the PCA. These results illustrate the molecular mechanisms by whichP. massonianacultivars resist or tolerate PWN and are of great significance in the prevention and control of PWD.
Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV
Authors: Chao Cara W. , Sprouse Kaitlin R. , Miranda Marcos C. , Catanzaro Nicholas J. , Hubbard Miranda L. , Addetia Amin , Stewart Cameron , Brown Jack T. , Dosey Annie , Valdez Adian , Ravichandran Rashmi , Hendricks Grace G. , Ahlrichs Maggie , Dobbins Craig , Hand Alexis , Treichel Catherine , Willoughby Isabelle , Walls Alexandra C. , McGuire Andrew T. , Leaf Elizabeth M. , Baric Ralph S. , Schäfer Alexandra , Veesler David , King Neil P. 
Published: March 2024

AbstractMiddle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2. Two-component protein nanoparticles displaying MERS-CoV S-derived antigens induced robust neutralizing antibody responses and protected mice against challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping and serum competition assays revealed the specificities of the dominant antibody responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle vaccine elicited antibodies targeting multiple non-overlapping epitopes in the RBD, whereas anti-NTD antibodies elicited by the S-2P– and NTD-based immunogens converged on a single antigenic site. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.
Exploiting WEE1 kinase activity as FUS::DDIT3-dependent therapeutic vulnerability in myxoid liposarcoma
Authors: Heinst Lorena , Lee Kwang Seok , Berthold Ruth , Isfort Ilka , Wosnig Svenja , Kuntze Anna , Hafner Susanne , Altvater Bianca , Rössig Claudia , Åman Pierre , Wardelmann Eva , Scholl Claudia , Hartmann Wolfgang , Fröhling Stefan , Trautmann Marcel 
Published: March 2024

AbstractThe pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. Since FUS::DDIT3 has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role of the cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS. Here we demonstrate that enhanced WEE1 pathway activity represents a hallmark of FUS::DDIT3-expressing cell lines as well as MLS tissue specimens and that WEE1 is required for MLS cellular survivalin vitroandin vivo. Pharmacologic inhibition of WEE1 activity results in DNA damage accumulation and cell cycle progression forcing cells to undergo apoptotic cell death. In addition, our results uncover FUS::DDIT3-dependent WEE1 expression as an oncogenic survival mechanism to tolerate high proliferation and resulting replication stress in MLS. Fusion protein-driven G1/S cell cycle checkpoint deregulation via overactive Cyclin E/CDK2 complexes thereby contributes to enhanced WEE1 inhibitor sensitivity in MLS. These findings identify WEE1-mediated replication stress tolerance as molecular vulnerability in FUS::DDIT3-driven MLS tumorigenesis that could represent a novel target for therapeutic intervention.
Viewing stomata in action: Autonomousin plantaimaging of individual stomatal movement
Authors: van den Berg Tomas E. , Sanders Remco G. P. , Kaiser Elias , Schmitz Jurriaan 
Published: March 2024

SummaryStomata regulate plant gas exchange under changing environments, but observations of the dynamics of single stomatain plantaare sparse. We developed a compact microscope system that can measure the kinetics of tens of stomatain plantasimultaneously, with sub-minute time resolution. Dark field imaging with green light was used to create 3D stacks from which 2D surface projection were constructed to resolve stomatal apertures within the field of view.Stomatal dynamics ofChrysanthemum morifolium (Chrysanthemum)andZea Mays(Maize) under dynamically changing light intensity were categorized, and a kinetic model was fitted to the data for quantitative comparison. In addition, we also resolved dynamics of the surface position of the leaf, related to dynamics of leaf thickness or bending.Maize stomata oscillated frequently between open and closed states under constant growth light and these oscillating stomata responded faster to changes in light than non-oscillating stomata at the same aperture.The slow closure of Chrysanthemum stomata reduced water use efficiency (WUE). Over 50% showed delayed or partial closure, leading to unnecessarily large apertures after reduced light. Stomata with larger apertures had more lag and similar closure speeds compared to those with smaller apertures and lag, further reducing WUE. In contrast, maize stomata with larger apertures closed faster, with no lag.In conclusion, our new system enables fine mapping of the heterogeneity of movement in neighboring stomata, providing new insights on the relations between stomatal dimensions, relative position and aperture changes under fluctuating light intensity.
Muscle fiber Myc is dispensable for muscle growth and forced expression severely perturbs homeostasis
Authors: Ham Daniel J. , Semeraro Michelangelo , Berger Bianca M. , Lin Shuo , Maino Eleonora , Oliveri Filippo , Rüegg Markus A. 
Published: March 2024

ABSTRACTThe oncogenic transcription factor Myc stimulates many growth processes including cell cycle progression and ribosome biogenesis. Myc expression is low in adult skeletal muscle, but is upregulated upon growth stimuli. Furthermore, muscle fiber Myc overexpression recapitulates many aspects of growth-related gene expression, suggesting Myc may mediate pro-growth responses to anabolic stimuli, such as exercise. Here, we tested this hypothesis by examining mouse models in which Myc was specifically eliminated or overexpressed in skeletal muscle fibers or muscle stem cells (MuSC). While muscle fiber Myc expression increased during muscle growth and Myc expression in MuSCs was required for successful muscle regeneration, muscle fiber Myc expression was dispensable for post-natal, mechanical overload or PKB/Akt-induced muscle growth in mice. Similarly, constitutive Myc expression did not promote skeletal muscle hypertrophy, but instead impaired muscle fiber structure and function within days. These data question the role of Myc in skeletal muscle growth.
Bayesian semantic surprise based on different types of regularities predicts the N400 and P600 brain signals
Authors: Hodapp Alice , Lindborg Alma , Rabovsky Milena 
Published: March 2024

AbstractThe brain’s remarkable ability to extract patterns from sequences of events has been demonstrated across cognitive domains and is a central assumption of predictive processing theories. While predictions shape language processing at the level of meaning, little is known about the underlying learning mechanism. Here, we investigated how continuous statistical inference in a semantic sequence influences the neural response. 60 participants were presented with a semantic oddball-like roving paradigm, consisting of sequences of nouns from different semantic categories. Unknown to the participants, the overall sequence contained an additional manipulation of transition probability between categories. Two Bayesian sequential learner models that captured different aspects of probabilistic learning were used to derive theoretical surprise levels for each trial and investigate online probabilistic semantic learning. The N400 ERP component was primarily modulated by increased probability with repeated exposure to the categories throughout the experiment, which essentially represents repetition suppression. This N400 repetition suppression likely prevented sizeable influences of more complex predictions such as those based on transition probability, as any incoming information was already continuously active in semantic memory. In contrast, the P600 was associated with semantic surprise in a transition probability model over recent observations, possibly indicating a working memory update in response to violations of these conditional dependencies. The results support probabilistic predictive processing of semantic information and demonstrate that continuous update of distinct statistics differentially influences language related ERPs.
N-acetylcysteine counteracts immune dysfunction and autistic-related behaviors in theShank3bmouse model of Autism Spectrum Disorders
Authors: Pangrazzi Luca , Cerilli Enrica , Balasco Luigi , Dall’O’ Ginevra Matilde , Chelini Gabriele , Pastore Anna , Weinberger Birgit , Bozzi Yuri 
Published: March 2024

AbstractAutism Spectrum Disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Here we reported that increased levels of molecules related to inflammation are present in the cerebellum and peripheral blood (PB) of mice lacking Shank3b, established model of syndromic ASD. In parallel, immune dysfunction was documented in the bone marrow (BM) and spleen of mutant mice. N-acetylcysteine (NAC) treatment rescued inflammation in the cerebellum and PB, as well as impaired production of pro-inflammatory molecules in the BM and spleen. In addition, social impairment was counteracted in NAC-treated Shank3b-/-animals. Taken together, our study further confirms the key role of cerebellar inflammation in the establishment of ASD-related behaviors. Furthermore, our findings underscore the importance of considering ASD as a systemic disorder.Our findings therefore suggest that the interplay between oxidative stress and inflammation may support ASD-related behaviors in mice.
CDK4is co-amplified with eitherTP53promoter gene fusions orMDM2through distinct mechanisms in osteosarcoma
Authors: Saba Karim H , Difilippo Valeria , Styring Emelie , Nilsson Jenny , Magnusson Linda , Bos Hilda van den , Spierings Diana C. J. , Foijer Floris , Nathrath Michaela , Haglund de Flon Felix , Baumhoer Daniel , Nord Karolin H 
Published: March 2024

AbstractAmplification of theMDM2andCDK4genes on chromosome 12 is commonly associated with low-grade osteosarcomas. In this study, we conducted high-resolution genomic and transcriptomic analyses on 33 samples from 25 osteosarcomas, encompassing both high- and low-grade cases withMDM2and/orCDK4amplification. We identified four major subgroups: (i) low-grade osteosarcoma with chromosome 12 amplicons as the sole acquired alteration, (ii) high- and low-grade tumours withCDK4andMDM2amplification along with few changes affecting other chromosomes, (iii) high-grade osteosarcomas with heavily rearranged genomes including eitherCDK4andMDM2amplification or (iv)CDK4amplification andTP53structural alterations. The amplicons involvingMDM2exhibited signs of an initial chromothripsis event affecting chromosome 12. In contrast, there was no indication of a chromothripsis event on chromosome 12 inTP53-rearranged cases. Instead, the initial disruption of theTP53locus resulted in breakage and repair processes that co-amplified theCDK4locus. Furthermore, our investigation revealed recurring promoter swapping events that involved the regulatory regions of theFRS2,PLEKHA5, andTP53genes. These events led to the ectopic expression of partner genes, with theELF1gene being upregulated by theFRS2andTP53promoter regions, respectively, in two distinct cases.
GEGA (Gallus Enriched Gene Annotation): an online tool providing genomics and functional information across 47 tissues for a chicken gene-enriched atlas gathering Ensembl & Refseq genome annotations
Authors: Degalez Fabien , Bardou Philippe , Lagarrigue Sandrine 
Published: March 2024

ABSTRACTGEGA is a user-friendly tool to navigate through different genomics and functional information related to an enriched gene atlas in chicken that unifies the gene catalogues from the two reference databases, NCBI-RefSeq & EMBL-Ensembl/GENCODE, and four other additional rich resources as FAANG and NONCODE. Using the latest GRCg7b genome assembly, GEGA offers a total of 78,323 genes, including 24,102 protein-coding genes (PCGs) and 44,428 long non-coding RNAs (lncRNAs), greatly enhancing the number of genes provided by each resource separately. But GEGA is more than just a gene database. It offers a range of features that allow to go deeper into the functional aspects of these genes,e.g., by exploring their expression and co-expression profiles across 47 tissues from 36 datasets and 1400 samples, by discovering tissue-specific variations and their expression as a function of sex or age, by extracting their orthologous genes or their configuration related to the genomics closest gene. For the communities interested in one specific gene, a list of genes or a QTL region in chicken, GEGA’s user-friendly interface enables efficient gene analysis, easy downloading of results and a multitude of graphical representations, from genomic information to detailed visualization of expression levels.GRAPHICAL ABSTRACT
Adoptive transfer of CD49a+Tissue resident memory cells reverses pulmonary fibrosis in mice
Authors: Collins Samuel L , Chan-Li Yee , Shenderov Kevin , Gillich Astrid , Nelson Andrew M. , Loube Jeffrey M. , Mitzner Wayne A , Powell Jonathan D. , Horton Maureen R. 
Published: March 2024

AbstractPulmonary fibrosis is a devastating disease with no effective treatments to cure, stop or reverse the unremitting, fatal fibrosis. A critical barrier to treating this disease is the lack of understanding of the pathways leading to fibrosis as well as those regulating the resolution of fibrosis. Fibrosis is the pathologic side of normal tissue repair that results when the normal wound healing programs go awry. Successful resolution of tissue injury requires several highly coordinated pathways, and this research focuses on the interplay between these overlapping pathways: immune effectors, inflammatory mediators and fibroproliferation in the resolution of fibrosis. Previously we have successfully prevented, mitigated, and even reversed established fibrosis using vaccinia vaccination immunotherapy in two models of murine lung fibrosis. The mechanism by which vaccinia reverses fibrosis is by vaccine induced lung specific Th1 skewed tissue resident memory (TRMs) in the lung. In this study, we isolated a population of vaccine induced TRMs - CD49a+CD4+T cells - that are both necessary and sufficient to reverse established pulmonary fibrosis. Using adoptive cellular therapy, we demonstrate that intratracheal administration of CD49a+CD4+TRMs into established fibrosis, reverses the fibrosis histologically, by promoting a decrease in collagen, and functionally, by improving lung function, without the need for vaccination. Furthermore, co-culture ofin vitroderived CD49+CD4+human TRMs with human fibroblasts from individuals with idiopathic pulmonary fibrosis (IPF) results in the down regulation of IPF fibroblast collagen production. Lastly, we demonstrate in human IPF lung histologic samples that CD49a+CD4+TRMs, which can down regulate human IPF fibroblast function, fail to increase in the IPF lungs, thus potentially failing to promote resolution. Thus, we define a novel unappreciated role for tissue resident memory T cells in regulating established lung fibrosis to promote resolution of fibrosis and re-establish lung homeostasis. We demonstrate that immunotherapy, in the form of adoptive transfer of CD49a+CD4+TRMs into the lungs of mice with established fibrosis, not only stops progression of the fibrosis but more importantly reverses the fibrosis. These studies provide the insight and preclinical rationale for a novel paradigm shifting approach of using cellular immunotherapy to treat lung fibrosis.
Distractor-response binding influences visual search
Authors: Allenmark Fredrik , Yu Hao , Müller Hermann J. , Shi Zhuanghua , Frings Christian 
Published: March 2024

AbstractIntertrial priming effects in visual search and action control suggest the involvement of binding and retrieval processes. However, the role of distractor-response binding (DRB) in visual search has been largely overlooked, and the specific processing stage within the functional architecture of attentional guidance where the DRB occurs remains unclear. To address these gaps, we implemented two search tasks, where participants responded based on a separate feature from the one defining the target. We kept the target dimension consistent across trials while varying the color and shape of the distractor. Moreover, we either repeated or randomized the target position in different sessions. Our results revealed a pronounced response priming, a difference between trials where the response changed vs. repeated: they were stronger when distractor features or the target position were repeated than they varied. Furthermore, the distractor feature priming, a difference between the distractor features repetition and switch, was contingent on the target position, suggesting that DRB likely operates at late stages of target identification and response selection. These insights affirm the presence of DRB during visual search and support the framework of binding and retrieval in action control as a basis for observed intertrial priming effects related to distractor features.Public significance statementThis study investigated inter-trial effects within visual search tasks and uncovered significant evidence for the role of distractor-response binding. This phenomenon involves linking a response in a given trial to the perceptual features (e.g. color and shape) of non-target items. Crucially, the study revealed that this distractor-response binding effect depends on whether the target location is repeated nearly repeated, suggesting that the retrieval of a previous response occurs at the later stages of target identification or response selection, even though non-target features likely are identified at an earlier stage.