bluuebunny/crossref_metadata_2025_split huggingface dataset:
CytoBatchNorm: an R package with graphical interface for batch effects correction of cytometry data
Authors: Granjeaud Samuel , Abdellaoui Naoill , Chrétien Anne-Sophie , Woitrain Eloise , Pineau Laurent , Ninni Sandro , Harari Alexandre , Arnaud Marion , Montaigne David , Staels Bart , Dombrowicz David , Molendi-Coste Olivier 
Published: June 2024

ABSTRACTInnovation in cytometry propelled it to an almost “omic” dimension technique during the last decade. The application fields concomitantly enlarged, resulting in generation of high-dimensional high-content data sets which have to be adequately designed, handled and analyzed. Experimental solutions and detailed data processing pipelines were developed to reduce both the staining conditions variability between samples and the number of tubes to handle. However, an unavoidable variability appears between samples, barcodes, series and instruments (in multicenter studies) contributing to “batch effects” that must be properly controlled. Computer aid to this aim is necessary, and several methods have been published so far, but configuring and carrying out batch normalization remains unintuitive for scientists with “pure” academic backgrounds in biology. To address this challenge, we developed an R package called CytoBatchNorm that offers an intuitive and user-friendly graphical interface. Although the processing is based on the script by Schuyler et al., the graphical interface revolutionizes its use. CytoBatchNorm enables users to define a specific correction for each marker in a single run. It provides a graph that guides you through quickly setting the correction for each marker. It allows corrections to be previewed and inter-marker effects to be checked as the settings are made. CytoBatchNorm will help the cytometry community to adequately scale data between batches, reliably reducing batch effects and improving subsequent dimension reduction and clustering.VISUAL ABSTRACT
A Novel Approach for Accurate Sequence Assembly Using de Bruijn graphs
Authors: Prybol Cameron J. , Hammack Aeron T. , Ashley Euan A. , Snyder Michael P. 
Published: June 2024

AbstractSequence assembly methods are valuable for reconstructing genomes from shorter read fragments. Modern nucleic acid sequencing instruments produce quality scores associated with each reported base; however, these quality scores are not generally used as a core part of sequence assembly or alignment algorithms. Here, we leverage weighted de Bruijn graphs as graphical probability models representing the relative abundances and qualities of kmers within FASTQ-encoded observations. We then utilize these weighted de Bruijn graphs to identify alternate, higher-likelihood candidate sequences compared to the original observations, which are known to contain errors. By improving the original observations with these resampled paths, iteratively across increasing k-lengths, we can use this expectation-maximization approach to “polish” read sets from any sequencing technology according to the mutual information shared in the reads. We use this polishing approach to probabilistically correct simulated short- and long-read datasets of lower coverages and higher error rates than some algorithms can produce satisfactory assemblies for. We find that this approach corrects sequencing errors at rates that are able to produce error-free and nearly-error-free de Bruijn assembly graphs for simulated read-set challenges.
Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy
Authors: Klenchin Vadim A. , Clark Natasha M. , Keles Nida K. , Capuano Saverio , Mason Rosemarie , Gao Guangping , Broman Aimee , Kose Emek , Immonen Taina T. , Fennessey Christine M. , Keele Brandon F. , Lifson Jeffrey D. , Roederer Mario , Gardner Matthew R. , Evans David T. 
Published: June 2024

AbstractAn alternative to lifelong antiretroviral therapy (ART) is needed to achieve durable control of HIV-1. Here we show that adeno-associated virus (AAV)-delivery of two rhesus macaque antibodies to the SIV envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected with barcoded SIVmac239M after discontinuing suppressive ART. Following AAV administration, sustained antibody expression with minimal anti-drug antibody responses was achieved in all but one animal. After ART withdrawal, SIV replication rebounded within two weeks in all of the control animals but remained below the threshold of detection in plasma (<15 copies/mL) for more than a year in four of the eight animals that received AAV vectors encoding Env-specific antibodies. Viral sequences from animals with delayed rebound exhibited restricted barcode diversity and antibody escape. Thus, sustained expression of antibodies with potent antiviral activity can afford durable, ART-free containment of pathogenic SIV infection.
Mutation Reporter: fast identification of mutations in NGS files
Authors: Teodoro Mikaela , Chagas Rosana V. das , Yunes José A. , Migita Natacha A. , Meidanis Joaõ 
Published: June 2024

ABSTRACTSummaryNext-generation sequencing (NGS) has accelerated precision medicine by enabling analysis of multiple genes at once and detection of low-frequency mutations. Nevertheless, there is a paucity of software applications enabling users not trained in bioinformatics to discern and adjust the quality parameters employed for analyzing sequencing data, which yield the output containing detected mutations alongside their corresponding variant allele frequency (VAF). Mutation Reporter was developed to identify point mutations, offering users the ability to adjust parameters including alignment e-value, minimum read size, minimum read depth, and minimum reported VAF.Availability and implementationMutation Reporter is available to users through a free GNU software license and can be accessed on GitHub (https://github.com/meidanis-lab/mutation-reporter) and as a Code Ocean capsule (https://codeocean.com/capsule/4682823/tree/v1).
Shiba: A versatile computational method for systematic identification of differential RNA splicing across platforms
Authors: Kubota Naoto , Chen Liang , Zheng Sika 
Published: June 2024

AbstractAlternative pre-mRNA splicing (AS) is a fundamental regulatory process that generates transcript diversity and cell type variation. We developed Shiba, a comprehensive method that integrates transcript assembly, splicing event identification, read counting, and differential splicing analysis across RNA-seq platforms. Shiba excels in capturing annotated and unannotated AS events with superior accuracy, sensitivity, and reproducibility. It addresses the often-overlooked issue of junction read imbalance, significantly reducing false positives to aid target prioritization and downstream analyses. Unlike other tools that require large numbers of biological replicates or resulting in low sensitivity and high false positives, Shiba’s statistics framework is agnostic to sample size, as demonstrated by simulated data and its effective application to realn=1 RNA-seq datasets. To extend its utility to single-cell RNA-seq, we developed scShiba, which applies Shiba’s pseudobulk approach to analyze splicing at the cluster level. scShiba successfully revealed AS regulation in developmental dopaminergic neurons and differences between excitatory and inhibitory neurons. Both Shiba and scShiba are available in Docker/Singularity containers and Snakemake pipelines, ensuring reproducibility. With their comprehensive capabilities, Shiba and scShiba enable systematic quantification of alternative splicing events across various platforms, laying a solid foundation for mechanistic exploration of the functional complexity in RNA splicing.
Structures of PSI-FCPI fromThalassiosira pseudonanain high light provide convergent evolution and light-adaptive strategies in diatom FCPIs
Authors: Feng Yue , Li Zhenhua , Yang Yang , Shen Lili , Li Xiaoyi , Liu Xueyang , Zhang Xiaofei , Zhang Jinyang , Ren Fei , Wang Yuan , Liu Cheng , Han Guangye , Wang Xuchu , Kuang Tingyun , Shen Jian-Ren , Wang Wenda 
Published: June 2024

AbstractDiatoms achieve great survival success in the fluctuating oceanic environment, rely on fucoxanthin chlorophylla/c-binding proteins (FCPs) to complete light harvesting and quenching, which provide about 20% primary productivity on earth. We report two cryo-electron microscopic structures of photosystem I (PSI) with 13 or 5 FCPIs respectively at 2.78 Å and 3.20 Å resolution fromThalassiosira pseudonanaunder high light conditions. 8 Lhcr FCPIs are found detached from the PSI-13FCPI supercomplex under high light conditions, remaining 5 FCPIs are stably combined with the PSI core including Lhcr3, RedCAP, Lhcq8, Lhcf10, and FCP3 subunits. The specific pigment network in this centric diatomT. pseudonanademonstrates a higher proportion of Chlorophyllsa, diadinoxanthins, and diatoxanthins but fewer fucoxanthins compared with the huge PSI-FCPI from another centric diatomChaetoceros gracilis, thus exhibiting more efficiency in energy transfer and dissipation among FCPI antennas. These results reveal the assembly mechanism of several types of peripheral FCPIs and corresponding light-adaptive strategies inT. pseudonana, as well as the convergent evolution of the diatoms PSI-FCPI structures.
Inhibition of Endothelial Lipase by MEDI5884 Normalizes Phosphatidylinositol Levels in Coronary Artery Disease Patients
Authors: Rosenbaum Anton I. , Huang Yue , Mu Ruipeng , Kovacina Kristina , Jin ChaoYu Denise , Hummer B. Timothy , Liang Meina , Grimsby Joseph S. 
Published: June 2024

AbstractBackgroundEndothelial lipase (EL) promotes high-density lipoproteins (HDL) phospholipid degradation, increases catabolism of HDL and is an attractive target for the potential treatment for cardiovascular disease. Inhibition of EL using a monoclonal neutralizing antibody, MEDI5884, demonstrated increased quantity and function of HDL. Determinants of anti-atherosclerotic function of HDL comprise the interplay of various components of HDL structure-activity relationship: size, shape and composition (lipid and protein). Previous studies have shown that single doses of MEDI5884 administered to healthy nonhuman primates (NHPs) and healthy subjects resulted in a dose- dependent increase in plasma phospholipids (PL) and that plasma PI levels in placebo treated healthy subjects are significantly increased relative to CAD subjects participating in clinical trialsNCT03001297andNCT03351738, respectively.MethodsHerein, we characterized using LC-MS/MS the plasma lipidome of NHPs, heathy subjects and subjects with coronary artery disease (CAD) following MEDI5884 administration.ResultsMEDI5884 treated NHPs resulted in a prominent increase in phosphatidylinositols (PI) and cholesteryl esters (CE). Treatment with MEDI5884 restores near-normal levels of PI in CAD patients. PI increases in both healthy subjects and CAD patients were dose-dependent, correlated with exposure and saturated at approximately 200 mg MEDI5884 subcutaneous (SC) dose in CAD patients. Comparison of pharmacodynamic (PD) effects of repeat SC 200 mg doses of MEDI5884 in CAD patients revealed greater and more rapid increases in PI levels compared to HDL-C and HDL phospholipid (HDL-PL). The increase in PI species was inversely correlated with decreases in free EL mass levels.ConclusionsPI has previously been shown to possess anti-atherosclerotic properties and led to increases in HDL cholesterol (HDL-C) and reverse cholesterol transport (RCT). The mechanism by which CE levels increase as the result of MEDI5884 administration can be attributed to the observed increase in both substrates of the lecithin-cholesterol acyltransferase (LCAT) reaction: phosphatidylcholine/phosphatidylethanolamine (PC/PE) and cholesterol as the consequence of EL inhibition. Further characterization of the underlying biological mechanisms responsible for the decrease of the PI biomarker in CAD patient population relative to healthy subjects as well as in conjunction with pharmacological intervention by MEDI5884 may reveal more information on this clinically-relevant biomarker and potential role in CAD.
A general approach to reduce off-target radioactivity in vivo via Tetrazine-Knock-Out (TKO)
Authors: Sarkar Swarbhanu , Pham Jonathan M. , Edwards Kimberly J. , Sharma Nitika , Xu Kexiang , King A. Paden , del Castillo Andres Fernandez , Farwell Michael D. , Pryma Daniel A. , Schuster Stephen J. , Sellmyer Mark A. 
Published: June 2024

AbstractMonoclonal antibodies have had a remarkable impact on cancer therapy due to their high target specificity. However, their large molecular weight results in slow blood clearance, which can take weeks to clear from circulation. As companion nuclear imaging and diagnostic tools, these characteristics force delayed imaging and the use of isotopes with long half-lives such as89Zr. For optimal clinical application, it is desirable that radioimmunoconjugates remain in the blood for just enough time to accumulate adequately in target tissues, while non-targeted or circulating radioactivity is ideally rapidly excreted from the body to maximize imaging contrast and minimize radiation dose to healthy tissues. We addressed the current challenges of antibody-based imaging by developing rituximab radioimmunoconjugates that accumulate sufficient activity for tumor imaging within 24 h of administration, while clearing circulating radioactivity via administration of a small molecule clearing agent. Rituximab, an anti-CD20 monoclonal antibody, is used as standard first-line therapy for diffuse large B-cell lymphoma. CD20 is expressed by 95% of B-lymphocytes and their malignant counterparts, making it a therapeutic target for B-cell malignancies. We attached125I,68Ga, and89Zr to rituximab using a “clickable” linker containingtrans-cyclooctene and tested the ability of tetrazines to induce the inverse electron demand Diels-Alder reaction (iEDDA) after antibody administration. This “tetrazine-knock-out” (TKO) approach liberates the radioactivity from rituximab in the bloodstream, resulting in its rapid renal excretion which enhances target-to-background ratios, and minimizes off-target radiation exposure. Due to the internalization of the radioimmunoconjugate in CD20+tumor cells, no substantial clearance was observed from Raji xenografts. We characterized different leaving groups, several cellular models and antibodies with distinct internalizaing properties. The TKO approach opens opportunities to use radiolabeled antibodies for low-abundance or heterogeneously expressed biologic targets and may allow radioimmunotherapy (RIT) for targets traditionally untenable due to dose-limiting toxicities.Graphical abstract
Low T cell diversity is associated with poor outcome in bladder cancer: a comprehensive longitudinal analysis of the T cell receptor repertoire
Authors: Kjær Asbjørn , Kristjánsdóttir Nanna , Juul Randi Istrup , Nordentoft Iver , Birkenkamp-Demtröder Karin , Ahrenfeldt Johanne , Strandgaard Trine , Radif Deema , Hodgson Darren , Abbosh Christopher , Aerts Hugo JWL , Agerbæk Mads , Jensen Jørgen Bjerggaard , Birkbak Nicolai J , Dyrskjøt Lars 
Published: June 2024

SummaryT cells are one of the primary effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. Here we investigated the clinical relevance of the T cell receptor (TCR) repertoire in patients with bladder cancer. In advanced-stage bladder cancer, low pre-treatment peripheral TCR diversity was associated with worse overall survival (p=0.024), particularly when it coincided with a low fraction of circulating T cells (p=0.00049). The low-diversity TCR repertoires were dominated by expanded clones that persisted throughout treatment and disproportionately targeted latent viral infections. Longitudinal analysis revealed a reduction in TCR diversity after treatment indicating an adverse effect on the immune system. In early-stage bladder cancer, we showed that immunotherapy had a stimulatory effect on TCR diversity in patients with good outcomes. Single-cell sequencing identified most expanded clones as cytotoxic T cells, while non-expanded clones were predominantly naive T cells. Overall, our findings suggest that TCR diversity is a promising new biomarker that may offer new avenues for tailored oncological treatment to enhance clinical outcomes for bladder cancer patients.
MULAN: Multimodal Protein Language Model for Sequence and Structure Encoding
Authors: Frolova Daria , Pak Marina A. , Litvin Anna , Sharov Ilya , Ivankov Dmitry N. , Oseledets Ivan 
Published: June 2024

AbstractMost protein language models (PLMs), which are used to produce high-quality protein representations, use only protein sequences during training. However, the known protein structure is crucial in many protein property prediction tasks, so there is a growing interest in incorporating the knowledge about the protein structure into a PLM. In this study, we propose MULAN, a MULtimodal PLM for both sequence and ANgle-based structure encoding. MULAN has a pre-trained sequence encoder and an introduced Structure Adapter, which are then fused and trained together. According to the evaluation on 7 downstream tasks of various nature, both small and medium-sized MULAN models show consistent improvement in quality compared to both sequence-only ESM-2 and structure-aware SaProt. Importantly, our model offers a cheap increase in the structural awareness of the protein representations due to finetuning of existing PLMs instead of training from scratch. We perform a detailed analysis of the proposed model and demonstrate its awareness of the protein structure. The implementation, training data and model checkpoints are available athttps://github.com/DFrolova/MULAN.
Surforama: interactive exploration of volumetric data by leveraging 3D surfaces
Authors: Yamauchi Kevin A. , Lamm Lorenz , Gaifas Lorenzo , Righetto Ricardo D. , Litvinov Daniil , Engel Benjamin D. , Harrington Kyle 
Published: June 2024

AbstractMotivationVisualization and annotation of segmented surfaces is of paramount importance for studying membrane proteins in their native cellular environment by cryogenic electron tomography (cryo-ET). Yet, analyzing membrane proteins and their organization is challenging due to their small sizes and the need to consider local context constrained to the membrane surface.ResultsTo interactively visualize, annotate, and analyze proteins in cellular context from cryo-ET data, we have developed Surforama, a Python package and napari plugin. For interactive visualization of membrane proteins in tomograms, Surforama renders the local densities projected on the surface of the segmentations. Suforama additionally provides tools to annotate and analyze particles on the membrane surfaces. Finally, for compatibility with other tools in the cryo-ET analysis ecosystem, results can be exported as RELION-formatted STAR files. As a demonstration, we performed subtomogram averaging and neighborhood analysis of photosystem II proteins in thylakoid membranes from the green algaChlamydomonas reinhardtii.Availability and implementationPython package, code and examples are available at:https://github.com/cellcanvas/surforama
Dissolution of Phosphate and Precipitation of Carbonate in the Biomineralization of the Bivalve Shell Limnoperna fortunei
Authors: Valadão Cardoso Antonio , Novaes Ferreira Rodrigo 
Published: June 2024

AbstractThe mantle of bivalves plays a crucial role in the formation and maintenance of their shells through biomineralization. Detailed studies using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) analysis have revealed the presence of phosphorus (P) compounds as the primary phase during biomineralization at the growing edge of the periostracum of the bivalve shell Limnoperna fortunei (Dunker, 1857). The presence of a crystal morphology like hydroxyapatite (HAp) at the growing edge of the shell has also been identified, and the Ca/P ratio compatible with HAp. Carbonic anhydrase (CA), whose presence in the shell was investigated in this work, and/or bivalve proteins with identical capability are likely responsible for the dissolution phosphate and calcium carbonate precipitation. Other experimental techniques (ICP-OES, WDXRF) were used to quantify the main chemical elements in the shell of L. fortunei and the marine bivalve P. perna. The concentration of P in the shells suggests that phosphate is confined to the growing regions. FTIR and FTIR-ATR spectroscopies indicate aragonite as the main phase at the shell edges but also show the presence of phosphate absorption bands. X-ray diffraction (XRD) analyses revealed aragonite and calcite phases at the shell edges, with the presence of one of the main peaks of crystalline calcium phosphate both in L. fortunei and P. perna. The presence of phosphate as the primary phase in the biomineralization process of L. fortunei rekindles the discussion about the importance of the co-occurrence of phosphate and carbonate in the bivalve biomineralization dynamics and suggests an important evolutionary advantage in acquiring phosphate compounds essential for energy production and organism function.
Antinociceptive synergy in a peripheral hyperalgesia model: interplay of cannabinoidergic, adrenergic, and opioidergic systems and their antagonism
Authors: Lopes Caio Fabio Baeta , Santos-Silva Thamyris , Fonseca Flávia Cristina , de Queiroz Bárbara Formiga Gonçalves , Duarte Igor Dimitri Gama , Romero Thiago Roberto Lima 
Published: June 2024

AbstractThere is growing interest in co-administering know analgesics for pain management, to reduce side effects and maximize therapeutic effects by pharmacological synergism, defined as supra-additive effects to biological stimuli. This work aimed to evaluate, using isobolgraphic analysis, synergistic effects of three antinociceptive substances— anandamide (AEA), a cannabinoid CB1 receptor agonist; xylazine (XYL), an adrenergic α2-receptor agonist; and DAMGO, an µ-opioid receptor agonist—administered in binary doses in a prostaglandin E2 (PGE2)-induced peripheral pain model. Hyperalgesia was induced in Swiss male mice, and subsequently, animals were treated with binary agonist combinations administered to the hind paw. Mechanical nociceptive thresholds were measured using an algesimetric task, and the results obtained were compared with additive predicted effects. For AEA+XYL and AEA+DAMGO combinations, the observed effects were significantly greater than those predicted by Loewe’s additivity principles at all tested effect levels (10%, 30%, and 50% maximum possible effect, MPE). DAMGO+XYL combination showed significant synergistic effects at 10% and 30% MPE but not at 50% MPE. Confirming these findings, combination indexes (CI) for AEA+XYL and AEA+DAMGO were less than 1, indicating synergism, while CI for DAMGO+XYL was near 1, indicating additivity. Notably, single-system antagonism with either AM251, a CB1 antagonist, yohimbine, an α2C-receptor antagonist or naloxone, pan-opioid receptor antagonist, could prevent synergy or any analgesia at all for AEA+XYL and AEA+DAMGO. Furthermore, the binary agonist combinations did not produce systemic effects, sedation, or motor impairments. The results suggest synergistic antinociceptive effects for AEA+XYL and AEA+DAMGO, which are dependent on concomitant agonism upon known metabotropic receptors.