bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microfluidic-enabled production of DNA barcoded APC library (MEDAL) for high throughput T cell epitope screening
Authors: Cui Xu , Liu Yi , Cheow Lih Feng 
Published: May 2024

AbstractScreening for peptide fragments that can be displayed on antigen-presenting cells is an essential step in vaccine development. The current approach for this process is slow and costly as it involves separately pulsing cells with chemically synthesized peptides. We present Microfluidic-Enabled production of DNA-barcoded APC Library (MEDAL), a high throughput microfluidic droplet platform for parallel production of DNA-barcoded APCs loaded with enzymatically synthesized peptides. Droplets containing peptides and their encoding DNA are produced from microfluidic PCR-IVTT reaction. APCs presenting both peptides and DNA barcodes are obtained by injecting cells into these droplets. Up to 9,000 different APCs can be produced and screened within a 10-hour workflow. This approach allowed us to identify peptide sequences that bind to APCs expressing H-2Kb MHC class 1 molecule with next-generation sequencing of DNA barcodes.
Spectral Cluster Supertree: fast and statistically robust merging of rooted phylogenetic trees
Authors: McArthur Robert N. , Zehmakan Ahad N. , Charleston Michael A. , Huttley Gavin 
Published: May 2024

AbstractThe algorithms for phylogenetic reconstruction are central to computational molecular evolution. The relentless pace of data acquisition has exposed their poor scalability and the conclusion that the conventional application of these methods is impractical and not justifiable from an energy usage perspective. Furthermore, the drive to improve the statistical performance of phylogenetic methods produces increasingly parameter-rich models of sequence evolution, which worsens the computational performance. Established theoretical and algorithmic results identify supertree methods as critical to divide-and-conquer strategies for improving scalability of phylogenetic reconstruction. Of particular importance is the ability to explicitly accommodating rooted topologies. These can arise from the more biologically plausible non-stationary models of sequence evolution.We make a contribution to addressing this challenge with Spectral Cluster Supertree, a novel supertree method for merging a set of overlapping rooted phylogenetic trees. It offers significant improvements over Min-Cut supertree and previous state-of-the-art methods in terms of both time complexity and overall topological accuracy, particularly for problems of large size. We perform comparisons against Min-Cut supertree and Bad Clade Deletion. Leveraging two tree topology distance metrics, we demonstrate that while Bad Clade Deletion generates more correct clades in its resulting supertree, Spectral Cluster Supertree’s generated tree is generally more topologically close to the true model tree. Over large datasets containing 10000 taxa and -500 source trees, where Bad Clade Deletion usually takes -2 hours to run, our method generates a supertree in on average 20 seconds. Spectral Cluster Supertree is released under an open source license and is available on the python package index assc-supertree.This research was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government.
Microbiome Modulation Uncouples Efficacy and Toxicity Induced by Programmed Death-1/Programmed Death-Ligand1 Blockade
Authors: Cogrossi Laura Lucia , Zordan Paola , Grioni Matteo , Tosi Anna , Rizzo Nathalie , Policastro Anna , Mattorre Benedetta , Lorenzoni Marco , Meregalli Greta , Sisti Sofia , Sanvito Francesca , Chesi Marta , Bergsagel Leif , Clementi Nicola , Rosato Antonio , Bellone Matteo 
Published: May 2024

AbstractWhile asymptomatic smoldering multiple myeloma (SMM) holds an overall risk of progression to multiple myeloma (MM) at 10% per year, only active surveillance is offered to most patients affected by SMM, which leaves them in anxiety and frustration. Intestinal microbiota and gut-born T helper 17 (Th17) lymphocytes may act as drivers of MM evolution. In transgenic Vk*MYC mice developingde novoMM, which invariably evolves from Early-MM that mimics SMM to full-blown Late-MM, we investigated the impact of gut microbiota modulation on disease progression and susceptibility to immune checkpoint blockade (ICB). We report that administering the human commensalPrevotella melaninogenicato mice affected by Early-MM significantly delayed evolution to Late-MM. Mechanistically, treatment withP. melaninogenicainduced increased production of short chain fatty acids. Butyrate prevented skew of dendritic cells towards a pro-Th17 phenotype and treated mice accumulated less disease induced Th17 cells in their bone marrow.P. melaninogenicaalso synergized with anti-PD-L1 antibodies by restraining Th17 cell expansion while unleashing ICB-induced full effector CD8+T cells, eventually blocking progression to full-blown disease. Similar results were obtained in mice challenged with bortezomib-resistant Vk*MYC tumor cells, a model of more aggressive MM. When mice were exposed to imiquimod to mimic ICB-associated psoriasis-like lesions,P. melaninogenicaameliorated skin lesions caused by ICB. Thus, modulation of the gut microbiota withP. melaninogenicamight represent a treatment for patients affected by SMM and would allow fully exploiting the antitumor potential of ICB in plasma cell dyscrasias.Key pointsAdministration of the human commensalPrevotella melaninogenicato Vk*MYC mice delayed evolution to symptomatic multiple myeloma;P. melaninogenicatherapeutically synergized with PD-1/PD-L1 blockade also limiting immune-related adverse events.
Human umbilical mesenchymal stem cell-derived mitochondria ameliorate maternal phenotype by improving placental mitochondria and vascular function in angiotensin II-induced preeclampsia rat
Authors: Cui Hui Xing , Liu Jun Xian , Kang Young Cheol , Han Kyuboem , Lee Hong Kyu , Kim Chun-Hyung , Zhang Yin Hua 
Published: May 2024

ABSTRACTBackgroundMitochondrial transplantation (Mito-T) is a novel therapeutic strategy targeting ischemic cardiovascular diseases. Here, we tested the efficacy of human umbilical mesenchymal stem cell-derived mitochondria transplantation (Mito-T) on a rat model of PE.MethodsPE was induced by infusing angiotensin II (Ang II) to SD pregnancy rats on gestation day 8 (GD 8). Mito-T (100 μg/μl) was injectedviajugular vein on GD 14.FindingsOn GD 20, PE rats showed high blood pressure, kidney and placental vascular abnormalities, reduced placental and fetal weights. Injected Mito-T was distributed intensively in the kidney, uterus and placenta of PE rats. Importantly, Mito-T reversed clinical manifestations of PE, restored placental abnormalities and reduced serum sFLT-1 levels and sFLT-1/PlGF ratio. In the placental mitochondria, Mito-T increased ETC complexes (complex I-V), improved mitochondrial membrane potential, ATP synthase and citrate synthase activities and biogenesis markers (PGC-1α, TFAM, NRF1) and reduced ROS production. Mito-T increased mitochondrial fusion proteins (OPA1, MFN1 and MFN2), reduced mitochondrial fission proteins (DRP1 and FIS1) and mitophagy proteins (PINK, BNIP3, BNIP3L, FUNDC1), restored sFLT-1 regulating calcineurin-NFAT-dependent pathways in the placental tissue, primary trophoblast cells and Bewo cell line. Furthermore, eNOS, nNOS and AT2R mRNA and protein expressions were restored in placenta and trophoblast cells after Mito-T.InterpretationThis is the first study of PE treatment with Mito-T. Mito-T reverses pathological phenotypes of PE rats by improving placental mitochondrial and vascular function. The results provide proofs of concept of Mito-T as a potential therapeutic strategy for reducing maternal and fetal risks in PE patients.FundingThis work is supported by Korean National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2019R1A2C1005720, NRF-2023R1A2C1005720), BK21 FOUR education program, Korean Society of Hypertension (Grant number KSH-R-2020), National Natural Science Foundation of China (NSFC 31660284, NSFC31860288).
Origins and diversity of pan-isotype human bone marrow plasma cells
Authors: Pacheco Gaspar A. , Rao Vishal , Yoo Duck Kyun , Saghaei Shahab , Tong Pei , Kumar Sachin , Marini-Rapoport Orlee , Allahyari Zahra , Moghaddam Ali S. , Esbati Romina , Alirezaee Aida , Parnes Aric , Patil Sarita U. , Wesemann Duane R. 
Published: May 2024

AbstractBone marrow plasma cells (BMPCs) produce durable, protective IgM, IgG, and IgA antibodies, and in some cases, pro-allergic IgE antibodies, but their properties and sources are unclear. We charted single BMPC transcriptional and clonal heterogeneity in food-allergic and non-allergic individuals across CD19 protein expression given its inverse correlation to BMPC longevity. Transcriptional and clonal diversity revealed distinct functional profiles. Additionally, distribution of somatic hypermutation and intraclonal antibody sequence variance suggest that CD19low and CD19high BMPCs arise from recalled memory and germinal center B cells, respectively. Most IgE BMPCs were from peanut-allergic individuals; two out of 32 from independent donors bound peanut antigens in vitro and in vivo. These findings shed light on BMPC origins and highlight the bone marrow as a source of pathogenic IgE in peanut allergy.
Genome assembly of the southern pine beetle (Dendroctonus frontalisZimmerman) reveals the origins of gene content reduction inDendroctonus
Authors: Copeland Megan , Landa Shelby , Owoyemi Adekola , Jonika Michelle M. , Alfieri Jamie , Sylvester Terrence , Hoover Zachary , Hjelmen Carl E. , Johnston J. Spencer , Kyre Bethany R. , Rieske Lynne K. , Blackmon Heath , Casola Claudio 
Published: May 2024

AbstractDendroctonus frontalis, also known as southern pine beetle (SPB), represents the most damaging forest pest in the southeastern United States. Strategies to predict, monitor and suppress SPB outbreaks have had limited success. Genomic data are critical to inform on pest biology and to identify molecular targets to develop improved management approaches. Here, we produced a chromosome-level genome assembly of SPB using long-read sequencing data. Synteny analyses confirmed the conservation of the core coleopteran Stevens elements and validated thebona fideSPB X chromosome. Transcriptomic data were used to obtain 39,588 transcripts corresponding to 13,354 putative protein-coding loci. Comparative analyses of gene content across 14 beetle and 3 other insects revealed several losses of conserved genes in theDendroctonusclade and gene gains in SPB andDendroctonusthat were enriched for loci encoding membrane proteins and extracellular matrix proteins. While lineage-specific gene losses contributed to the gene content reduction observed inDendroctonus, we also showed that widespread misannotation of transposable elements represents a major cause of the apparent gene expansion in several non-Dendroctonusspecies. Our findings uncovered distinctive features of the SPB gene complement and disentangled the role of biological and annotation-related factors contributing to gene content variation across beetles.
Recovery mode: Marine protected areas enhance the resilience of kelp species from marine heatwaves
Authors: Olguín-Jacobson Carolina , Arafeh-Dalmau Nur , Early-Capistrán Michelle-María , Montes José Antonio Espinoza , Hernández-Velasco Arturo , Martínez Ramón , Romero Alfonso , Torre Jorge , Woodson C. Brock , Micheli Fiorenza 
Published: May 2024

AbstractMarine protected areas (MPAs) can promote population recovery from climate change impacts by reducing local stressors, such as fishing. However, with extreme climatic events such as marine heatwaves (MHWs) increasing in frequency and duration, it remains unclear whether MPAs enhance recovery following these acute perturbations, and how recovery varies across species and ecological traits (e.g., sedentary vs mobile species). We used 16 years (2007-2022) of kelp forest monitoring data in Isla Natividad, Baja California Sur, Mexico, to assess the impact of the 2014-2016 MHWs on fish and invertebrate communities. Then we evaluated the impact and recovery from the MHWs of economically and ecologically important invertebrate species inside and outside two fully protected marine reserves. We found that the 2014-2016 MHWs, which were the most intense and persistent ever observed in Isla Natividad, impacted invertebrates but not fish biomass. Marine reserves did not confer resistance to the MHWs, however, reserves did enhance the recovery of some species after the MHWs. Inside marine reserves, abalone (Haliotisspp.) and wavy turban snail (Megastraeaspp.) (benthic sedentary invertebrates) recovered to pre-heatwave biomass after two years and spiny lobster (Panulirus interruptus) (benthic mobile invertebrate) after four years. Outside the reserves, abalone recovered after three years, while the other two species never recovered. The warty sea cucumber (Apostichopus parvimensis) population collapsed after the MHWs and never recovered inside nor outside the reserve. Remarkably, abalone biomass had an outstanding and sustained recovery inside reserves, with a 5.6-fold increase in biomass after the MHWs, which was over three times higher than the recovery reported outside the reserve. Our analysis of long-term monitoring data shows that marine reserves cannot prevent adverse impacts from extreme climatic events but can enhance species recovery following these events. Benefits conferred by marine reserves, however, are species-specific and may be limited to species with limited dispersal and localized population dynamics.
Direct inference of the distribution of fitness effects of spontaneous mutations from recombinant inbredC. elegansmutation accumulation lines
Authors: Crombie Timothy A. , Rajaei Moein , Saxena Ayush S. , Johnson Lindsay M. , Saber Sayran , Tanny Robyn E. , Ponciano José Miguel , Andersen Erik C. , Zhou Juannan , Baer Charles F. 
Published: May 2024

AbstractThe distribution of fitness effects (DFE) of new mutations plays a central role in evolutionary biology. Estimates of the DFE from experimental Mutation Accumulation (MA) lines are compromised by the complete linkage disequilibrium (LD) between mutations in different lines. To reduce LD, we constructed two sets of recombinant inbred lines from a cross of twoC. elegansMA lines. One set of lines (“RIAILs”) was intercrossed for ten generations prior to ten generations of selfing; the second set of lines (“RILs”) omitted the intercrossing. Residual LD in the RIAILs is much less than in the RILs, which affects the inferred DFE when the sets of lines are analyzed separately. The best-fit model estimated from all lines (RIAILs + RILs) infers a large fraction of mutations with positive effects (∼40%); models that constrain mutations to have negative effects fit much worse. The conclusion is the same using only the RILs. For the RIAILs, however, models that constrain mutations to have negative effects fit nearly as well as models that allow positive effects. When mutations in high LD are pooled into haplotypes, the inferred DFE becomes increasingly negative-skewed and leptokurtic. We conclude that the conventional wisdom - most mutations have effects near zero, a handful of mutations have effects that are substantially negative and mutations with positive effects are very rare – is likely correct, and that unless it can be shown otherwise, estimates of the DFE that infer a substantial fraction of mutations with positive effects are likely confounded by LD.
Microbial network inference for longitudinal microbiome studies with LUPINE
Authors: Kodikara Saritha , Lê Cao Kim-Anh 
Published: May 2024

AbstractThe microbiome is a complex ecosystem of interdependent taxa that has traditionally been studied through cross-sectional studies. However, longitudinal microbiome studies are becoming increasingly popular. These studies enable researchers to infer taxa associations towards the understanding of coexistence, competition, and collaboration between microbes across time. Traditional metrics for association analysis, such as correlation, are limited due to the data characteristics of microbiome data (sparse, compositional, multivariate). Several network inference methods have been proposed, but have been largely unexplored in a longitudinal setting.We introduce LUPINE (LongitUdinal modelling with Partial least squares regression for NEtwork inference), a novel approach that leverages on conditional independence and low-dimensional data representation. This method is specifically designed to handle scenarios with small sample sizes and small number of time points. LUPINE is the first method of its kind to infer microbial networks across time, while considering information from all past time points and is thus able to capture dynamic microbial interactions that evolve over time. We validate LUPINE and its variant, LUPINE single (for single time point analysis) in simulated data and four case studies, where we highlight LUPINE’s ability to identify relevant taxa in each study context, across different experimental designs (mouse and human studies, with or without interventions, as short or long time courses). We propose different metrics to compare the inferred networks and detect changes in the networks across time, groups or in response to external disturbances.LUPINE is a simple yet innovative network inference methodology that is suitable for, but not limited to, analysing longitudinal microbiome data. The R code and data are publicly available for readers interested in applying these new methods to their studies.
The potential impacts of vector host species fidelity on zoonotic arbovirus transmission
Authors: Sulaimon Tijani A. , Wood Anthony J. , Bonsall Michael B. , Boots Michael , Lord Jennifer S. 
Published: May 2024

ABSTRACTThe interaction between vector host preference and host availability on vector blood feeding behaviour has important implications for the transmission of vector-borne pathogens. In particular in multi-host disease systems the fidelity of the vector biting behaviour has the potential to have important implications to disease outcomes, particularly when there are amplifying and dead-end hosts. Using a mathematical model we showed that vector fidelity to the host species they take a first blood meal from leads to non-homogeneous mixing between hosts and vectors. Taking Japanese encephalitis virus (JEV) as a case study, we investigated how vector preference for amplifying vs dead-end hosts and fidelity can influence JEV transmission. We show that in regions where pigs (amplifying hosts) are scarce compared to cattle (dead-end hosts preferred by common JEV vectors), JEV can still be maintained through vector fidelity. Our findings demonstrate the importance of considering fidelity as a potential driver of transmission, particularly in scenarios such as Bangladesh and India where the composition of the host community might initially suggest that transmission is not possible.
wgbstools: A computational suite for DNA methylation sequencing data representation, visualization, and analysis
Authors: Loyfer Netanel , Rosenski Jonathan , Kaplan Tommy 
Published: May 2024

AbstractNext-generation methylation-aware sequencing of DNA sheds light on the fundamental role of methylation in cellular function in health and disease. These data are commonly represented at a single CpG resolution, while single-molecule fragment-level analysis is often overlooked.Here, we presentwgbstools, an extensive computational suite tailored for methylation sequencing data. wgbstools allows fast access and ultra-compact anonymized representation of high-throughput methylome data, obtained through various library preparation and sequencing methods. Additionally,wgbstoolscontains state-of-the-art algorithms for genomic segmentation, biomarker identification, genetic and epigenetic data integration, and more. wgbstools offers fragment-level analysis and informative visualizations, across multiple genomic regions and samples.
TITINdb2 – Expanding Annotation and Structural Information for Protein Variants in the Giant Sarcomeric Protein Titin
Authors: Weston T. , Ng J. C-F. , Gracia Carmona O. , Gautel M. , Fraternali F. 
Published: May 2024

Structured AbstractSummaryWe present TITINdb2, an update to the TITINdb database previously constructed to facilitate the identification of pathogenic missense variants in the giant protein titin, which are associated with a variety of skeletal and cardiac myopathies. The database and web portal have been substantially revised and include the following new features: (i) an increase in computational annotation from 4 to 20 variant impact predictors, available through a new custom data table dialogue; (ii) thorough structural coverage of single domains with AlphaFold2 predicted models; (iii) newly predicted domain-domain interface annotations; (iv) an expandedin silicosaturation mutagenesis incorporating 4 variant impact predictors; (v) a comprehensive overhaul of available data, including population data sources and variants reported pathogenic in the literature; (vi) A curated mapping of existing protein, transcript and chromosomal sequence positions and a new variant conversion tool to translate variants in one format to any other format.Availability and ImplementationDatabase accessible via titindb.kcl.ac.uk/TITINdb/ContactFranca Fraternali (f.fraternali@ucl.ac.uk)Supplementary InformationAvailable
Proteins with proximal-distal asymmetries in axoneme localisation control flagellum beat frequency
Authors: Fort Cecile , Walker Benjamin J. , Baert Lore , Wheeler Richard John 
Published: May 2024

AbstractThe 9+2 microtubule-based axoneme within motile flagella is well known for its symmetry. However, examples of asymmetric structures and proteins asymmetrically positioned within the 9+2 axoneme architecture have been identified in multiple different organisms, particularly involving the inner or outer dynein arms, with a range of functions. Here, mapped, genome-wide, conserved proximal-distal asymmetries in the uniflagellate trypanosomatid eukaryotic parasites. Building on the genome-wide localisation screen inTrypanosoma bruceiwe identified conserved proteins with an analogous asymmetric localisation in the related parasiteLeishmania mexicana. Using deletion mutants, we map which are necessary for normal cell swimming, flagellum beat parameters and axoneme ultrastructure, and using combinatorial endogenous fluorescent tagging and deletion, map co-dependencies for assembly into their normal asymmetric localisation. This revealed 15 proteins, 8 known and 7 novels, with a conserved proximal or distal axoneme-specific localisation. Most were outer dynein arm associated, and showed that there are at least two distinct classes of proximal-distal asymmetry – one dependent on the docking complex, and one independent. Many were necessary for normal frequency of the tip-to-base symmetric flagellar waveform, and our comprehensive mapping reveals unexpected contribution of proximal-specific axoneme components to frequency of distal waveform initiation.