bluuebunny/crossref_metadata_2025_split huggingface dataset:
The resurrection of Cerasommatidiidae, an enigmatic group of coccinelloid beetles (Coleoptera: Coccinelloidea) based on molecular and morphological evidence
Authors: Arriaga-Varela Emmanuel , Tomaszewska Wioletta , Szawaryn Karol , Robertson James , Seidel Matthias , Ślipiński Adam , Fikáček Martin 
Published: November 2022

Abstract
The family Cerasommatidiidae was proposed by Brèthes in 1925 for his new genus Cerasommatidia from Brazil, described as an intermediate taxon between Endomychidae and Coccinellidae (Coccinelloidea). This group was neglected for decades until 1994 when the resemblance of Cerasommatidia with the eupsilobiine genus Ibicarella was noticed, and Cerasommatidiidae was synonymized with Eupsilobiinae (Endomychidae). Based on the newly discovered material from the Neotropical and Afrotropical regions with clear resemblance to Cerasommatidia and Ibicarella, the phylogenetic placement of these taxa and new allied genera was reassessed based on phylogenetic analyses of molecular, morphological and combined datasets. The data were analysed under Bayesian (BI), maximum likelihood (ML) and parsimony (MP) frameworks. Our results support the restoration of Cerasommatidiidae as a distinct family in Coccinelloidea. Close affinity of Cerasommatidiidae with Coccinellidae, Eupsilobiidae and Mycetaeidae is recovered and the sister-relationship to Mycetaeidae is highly supported. Ibicarella is found to be a junior synonym of Cerasommatidia. Three new genera and six new species are described and illustrated: Yamuy gen. nov. (type species, Y. marginatus sp. nov.; and Y. constratus sp. nov.) and Karumbe gen. nov. (type species, K. geiseri sp. nov.; K. brethesi sp. nov. and K. pakaluki sp. nov.) from the Neotropics and Mahavelo gen. nov. (type species, M. madagasus sp. nov.) from Madagascar.
Finding Haplotypic Signatures in Proteins
Authors: Vašíček Jakub , Skiadopoulou Dafni , Kuznetsova Ksenia G. , Wen Bo , Johansson Stefan , Njølstad Pål R. , Bruckner Stefan , Käll Lukas , Vaudel Marc 
Published: November 2022

AbstractThe non-random distribution of alleles of common genomic variants produces haplotypes, which are fundamental in medical and population genetic studies. Consequently, protein-coding genes with different co-occurring sets of alleles can encode different amino acid sequences: protein haplotypes. These protein haplotypes are present in biological samples, and detectable by mass spectrometry, but are not accounted for in proteomic searches. Consequently, the impact of haplotypic variation on the results of proteomic searches, and the discoverability of peptides specific to haplotypes remain unknown. Here, we study how common genetic haplotypes influence the proteomic search space and investigate the possibility to match peptides containing multiple amino acid substitutions to a publicly available data set of mass spectra. We found that for 9.96 % of the discoverable amino acid substitutions encoded by common haplotypes, two or more substitutions may co-occur in the same peptide after tryptic digestion of the protein haplotypes. We identified 342 spectra that matched to such multi-variant peptides, and out of the 4,251 amino acid substitutions identified, 6.63 % were covered by multi-variant peptides. However, the evaluation of the reliability of these matches remains challenging, suggesting that refined error rate estimation procedures are needed for such complex proteomic searches. As these become available and the ability to analyze protein haplotypes increases, we anticipate that proteomics will provide new information on the consequences of common variation, across tissues and time.
HAPPY: A deep learning pipeline for mapping cell-to-tissue graphs across placenta histology whole slide images
Authors: Vanea Claudia , Džigurski Jelisaveta , Rukins Valentina , Dodi Omri , Siigur Siim , Salumäe Liis , Meir Karen , Parks W. Tony , Hochner-Celnikier Drorith , Fraser Abigail , Hochner Hagit , Laisk Triin , Ernst Linda M. , Lindgren Cecilia M. , Nellåker Christoffer 
Published: November 2022

AbstractAccurate placenta pathology assessment is essential for managing maternal and newborn health, but the placenta’s heterogeneity and temporal variability pose challenges for histology analysis. To address this issue, we developed the ‘Histology Analysis Pipeline.PY’ (HAPPY), a deep learning hierarchical method for quantifying the variability of cells and micro-anatomical tissue structures across placenta histology whole slide images. HAPPY differs from patch-based features or segmentation approaches by following an interpretable biological hierarchy, representing cells and cellular communities within tissues at a single-cell resolution across whole slide images. We present a set of quantitative metrics from healthy term placentas as a baseline for future assessments of placenta health and we show how these metrics deviate in placentas with clinically significant placental infarction. HAPPY’s cell and tissue predictions closely replicate those from independent clinical experts and placental biology literature.
CLARUS: An Interactive Explainable AI Platform for Manual Counterfactuals in Graph Neural Networks
Authors: Beinecke Jacqueline , Saranti Anna , Angerschmid Alessa , Pfeifer Bastian , Klemt Vanessa , Holzinger Andreas , Hauschild Anne-Christin 
Published: November 2022

AbstractBackgroundLack of trust in artificial intelligence (AI) models in medicine is still the key blockage for the use of AI in clinical decision support systems (CDSS). Although AI models are already performing excellently in systems medicine, their black-box nature entails that patient-specific decisions are incomprehensible for the physician. This is especially true for very complex models such as graph neural networks (GNNs), a common state-of-the-art approach to model biological networks such as protein-protein-interaction graphs (PPIs) to predict clinical outcomes. The aim of explainable AI (XAI) algorithms is to “explain” to a human domain expert, which input features, such as genes, influenced a specific recommendation. However, in the clinical domain, it is essential that these explanations lead to some degree of causal understanding by a clinician in the context of a specific application.ResultsWe developed the CLARUS platform, aiming to promote human understanding of GNN predictions by allowing the domain expert to validate and improve the decision-making process. CLARUS enables the visualisation of the patient-specific biological networks used to train and test the GNN model, where nodes and edges correspond to gene products and their interactions, for instance. XAI methods, such as GNNExplainer, compute relevance values for genes and interactions. The CLARUS graph visualisation highlights gene and interaction relevances by color intensity and line thickness, respectively. This enables domain experts to gain deeper insights into the biological network by identifying the most influential sub-graphs and molecular pathways crucial for the decision-making process. More importantly, the expert can interactively alter the patient-specific PPI network based on the acquired understanding and initiate re-prediction or retraining. This interactivity allows to ask manual counterfactual questions and analyse the resulting effects on the GNN prediction.ConclusionTo the best of our knowledge, we present the first interactive XAI platform prototype, CLARUS, that allows not only the evaluation of specific human counterfactual questions based on user-defined alterations of patient PPI networks and a re-prediction of the clinical outcome but also a retraining of the entire GNN after changing the underlying graph structures. The platform is currently hosted by the GWDG onhttps://rshiny.gwdg.de/apps/clarus/.
Variation in near-surface soil temperature drives plant assemblage insurance potential
Authors: Simpson Elizabeth G. , Fraser Ian , Woolf Hillary , Pearse William D. 
Published: November 2022

AbstractStudying how assemblages vary across environmental gradients provides a baseline for how assemblages may respond to climate change. Per the biological insurance hypothesis, assemblages with more variation in functional diversity will maintain ecosystem functions when species are lost. In complement, environmental heterogeneity supports landscape-scale ecosystem functionality (i.e. spatial insurance), when that variation includes environments with more abundant resources.We use the relationship between vascular plant functional diversity and microenvironment to identify where assemblages are most likely to maintain functionality in a mountainous fieldsite in northeastern Utah, USA. We assessed how life history strategies and information about phylogenetic differences affect these diversity-environment relationships.We found less functionally dispersed assemblages, that were shorter and more resource-conservative on hotter, more variable, south-facing slopes. In contrast, we found more functionally dispersed assemblages, that were taller and more resource-acquisitive on cooler, less variable, north-facing slopes. Herbaceous and woody perennials drove these trends. Additionally, including information about phylogenetic differences in a dispersion metric indicated that phylogeny accounts for traits we did not measure.Synthesis. At our fieldsite, soil temperature acts as an environmental filter across aspect. If soil temperature increases and becomes more variable, the function of north- vs. south-facing assemblages may be at risk for contrasting reasons. On south-facing slopes, assemblages may not have the variance in functional diversity needed to respond to more intense, stressful conditions. Conversely, assemblages on north-facing slopes may not have the resource-conservative strategies needed to persist if temperatures become hotter and more variable. We suggest that studying dispersal traits, especially of perennial species, will provide additional insight into whether this landscape will maintain function as climate changes.
Bioresorbable Mesenchymal Stem Cell–Loaded Electrospun Polymeric Scaffold Inhibits Neointimal Hyperplasia Following Arteriovenous Fistula Formation in a Rat Model of Chronic Kidney Disease
Authors: Barcena Allan John R. , Perez Joy Vanessa D. , Bernardino Marvin R. , Damasco Jossana A. , Cortes Andrea , Del Mundo Huckie C. , San Valentin Erin Marie D. , Klusman Carleigh , Canlas Gino Martin , Heralde Francisco M. , Avritscher Rony , Fowlkes Natalie , Bouchard Richard R. , Cheng Jizhong , Huang Steven Y. , Melancon Marites P. 
Published: November 2022

ABSTRACTIn the setting of chronic kidney disease (CKD), the periadventitial injection of mesenchymal stem cells (MSCs) has shown significant potential in improving arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). However, the rapid clearance of MSCs remains a challenge. Hence, we fabricated an electrospun perivascular scaffold from polycaprolactone (PCL) to support MSC attachment and allow gradual MSC elution at the outflow vein, the AVF site most prone to NIH. We performed a 5/6thnephrectomy to induce CKD in Sprague-Dawley rats, followed by direct AVF formation and perivascular scaffold application. We then compared the following groups of CKD rats: no perivascular scaffold (i.e., control), PCL scaffold, and PCL+MSC scaffold. On ultrasonography, the PCL and PCL+MSC groups showed significantly reduced wall thickness and wall-to-lumen ratio and increased luminal diameter and flow rate. Of note, the PCL+MSC group showed greater improvement in luminal diameter and flow rate compared to PCL alone. Moreover,18F-fluorodeoxyglucose positron emission tomography showed that only PCL+MSC resulted in a significant reduction in uptake. On histology, the PCL and PCL+MSC groups showed significantly reduced neointima-to-lumen and neointima-to-media ratios and reduced neointimal CD45, α-SMA, and vimentin fluorescence staining compared to the control. Although the two scaffold treatments did not differ significantly in histology, in vivo imaging suggested that the addition of MSCs promoted greater luminal expansion and blood flow and reduced the inflammatory process underlying NIH. Our results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.
k2v: A Containerized Workflow for Creating VCF Files from Kintelligence Targeted Sequencing Data
Authors: Turner Stephen D. , Peck Michelle A. 
Published: November 2022

AbstractThe ForenSeq Kintelligence kit developed by Verogen is a targeted Illumina sequencing assay that genotypes 10,230 single nucleotide polymorphisms designed for forensic genetic genealogy, forensic DNA phenotyping, and ancestry inference. We developedk2v, a containerized workflow for creating standard specification-compliant variant call format (VCF) files from the custom output data produced by the Kintelligence Universal Analysis Software. VCF files produced withk2venable the use of many pre-existing, widely used, community-developed tools for manipulating and analyzing genetic data in the standard VCF format. Here we describe thek2vimplementation, demonstrate its usage, and use the VCF produced byk2vto demonstrate downstream analyses that can easily be performed with pre-existing tools using VCF data as input: concordance analysis, ancestry inference, and relationship estimation.k2vis distributed as a Docker container available on Docker Hub. Documentation and source code fork2vis freely available under the GNU Public License (GPL-3.0) athttps://github.com/signaturescience/k2v.
excluderanges: exclusion sets for T2T-CHM13, GRCm39, and other genome assemblies
Authors: Ogata Jonathan D. , Mu Wancen , Davis Eric S. , Xue Bingjie , Harrell J. Chuck , Sheffield Nathan C. , Phanstiel Douglas H. , Love Michael I. , Dozmorov Mikhail G. 
Published: November 2022

AbstractSummaryExclusion regions are sections of reference genomes with abnormal pileups of short sequencing reads. Removing reads overlapping them improves biological signal, and these benefits are most pronounced in differential analysis settings. Several labs created exclusion region sets, available primarily through ENCODE and Github. However, the variety of exclusion sets creates uncertainty which sets to use. Furthermore, gap regions (e.g., centromeres, telomeres, short arms) create additional considerations in generating exclusion sets. We generated exclusion sets for the latest human T2T-CHM13 and mouse GRCm39 genomes and systematically assembled and annotated these and other sets in theexcluderangesR/Bioconductor data package, also accessible via the BEDbase.org API. The package provides unified access to 82 GenomicRanges objects covering six organisms, multiple genome assemblies and types of exclusion regions. For human hg38 genome assembly, we recommendhg38.Kundaje.GRCh38_unified_blacklistas the most well-curated and annotated, and sets generated by the Blacklist tool for other organisms.Availability and implementationhttps://bioconductor.org/packages/excluderanges/ContactMikhail G. Dozmorov (mdozmorov@vcu.edu)Supplementary informationPackage website:https://dozmorovlab.github.io/excluderanges/
Differential requirement ofnanoshomologs in the germline suggests the evolutionary path toward an inheritance mechanism of primordial germ cell formation in the silkmothBombyx
Authors: Nakao Hajime , Takasu Yoko 
Published: November 2022

AbstractThe lepidopteran insectBombyx moripossesses unique embryogenesis characteristics among insects.nanos(nos) has conserved functions in metazoan primordial germ cell formation.Bombyxpossesses fournosgenes (M, N, O, P), a unique feature found in lepidopterans examined so far. Of these, maternalnosOmRNA exhibits a localization pattern: it may act as a primordial germ cell (PGC) determinant. A previous knock-out experiment ofnosOshowed that this localized mRNA is dispensable for PGC formation in laboratory environment and has limited involvement in PGC specification. This study examined whether other nos genes act redundantly withnosOin germline using RNAi and gene editing. Although individual embryonic RNAi exhibited no detectable phenotypic alterations, simultaneous RNAi ofnosO/nosPmarkedly reduced oocyte number and male fecundity. Additionally,nosPKO almost completely sterilized both sexes. BecausenosPis broadly expressed in the posterior of embryos in non-germline specific manner, these results could reflect an evolutionary step taken byBombyxtoward its unique inheritance mechanisms. This study also suggests thatnosgenes inBombyxdo not affect anterior-posterior axis specification. This could reflect its characteristic embryogenesis.
Re-evaluating management of established pests including the European wasp,Vespula germanicausing biocontrol agents
Authors: Cacho Oscar , Hester Susie , Tait Peter , Kwong Raelene , Lefoe Greg , Rutherford Paul , Kriticos Darren 
Published: November 2022

AbstractEstablished pests such as the European wasp (Vespula germanica) are often overlooked as candidates for management programmes (eradication and/or containment) because the use of traditional surveillance and control techniques over very large areas becomes uneconomic. Use of biological control agents that persist in the environment is usually the only economically feasible option, however the processes around approvals for release of biocontrol agents can take significant amounts of time and resources, especially if screening and testing of potential agents is required.This project investigates whether the European wasp could be a candidate for a renewed management programme in south-eastern Australia given the availability of a biocontrol agent following successful screening and testing of an agent,Sphecophaga vesparum vesparum, in the 1980s. Whether a biological control programme is worthwhile pursuing depends on the size of the benefits to industry, community and the environment from a reduction in European wasp abundance. This project explores the benefits and costs of European wasp management using a biocontrol agent, and importantly, includes valuation of the social and environmental impacts of the pest.
Structure and function ofPlasmodiumactin II in the parasite mosquito stages
Authors: Lopez Andrea J. , Andreadaki Maria , Vahokoski Juha , Deligianni Elena , Calder Lesley J. , Camerini Serena , Freitag Anika , Bergmann Ulrich , Rosenthal Peter B. , Sidén-Kiamos Inga , Kursula Inari 
Published: November 2022

AbstractActins are filament-forming, highly-conserved proteins in eukaryotes. They are involved in essential processes in the cytoplasm and have also nuclear functions. Malaria parasites (Plasmodiumspp.) have two actin isoforms that differ from each other and from canonical actins in structure and filament-forming properties. Actin I has an essential role in motility and is fairly well characterized. The structure and function of actin II are not as well understood, but mutational analyses have revealed two essential functions in male gametogenesis and in the zygote. Here, we present expression analysis, high-resolution filament structures, and biochemical characterization ofPlasmodiumactin II. We show that it is expressed in male gametocytes and zygotes and associated with the nucleus in both stages in filament-like structures. Unlike actin I, actin II readily forms long filamentsin vitro, and near-atomic structures in the presence or absence of jasplakinolide reveal very similar structures. Small but significant differences compared to other actins in the openness and twist, the active site, the D-loop, and the plug region contribute to filament stability. Mutational analyses suggest that long and stable filaments are necessary for male gametogenesis, while the second function in the zygote stage also requires finetuned regulation by methylation of histidine 73. Actin II polymerizesviathe classical nucleation-elongation mechanism and has a critical concentration of ~0.1 μM at the steady-state, like actin I and canonical actins. Similarly to actin I, dimers are a stable form of actin II at equilibrium.Significance statementMalaria is a parasitic infection caused byPlasmodiumspp., which belong to the phylum Apicomplexa. In 2020, approximately 627000 people died from nearly 241 million malaria cases registered worldwide. In contrast to other apicomplexan parasites,Plasmodiumspp. encode two actin isoforms. While actin I is part of the glideosome complex, essential for locomotion, actin II is present in the mosquito stages, where it has functions in gametogenesis and in the zygote. The exact function of actin II is still unclear, and information at the molecular level is limited. We show here that actin II is associated with the nucleus in gametocytes and zygotes and performs specific functions requiring both long filaments and fine-tuning by methylation of histidine 73. We determined the structures of the filamentous form of actin II at near-atomic resolution and characterized its polymerization propertiesin vitro. Our study provides a molecular basis for the differences between actins of the malaria parasite and humans, as well as between the two parasite actin isoforms. Furthermore, thein vivostudies provide insights into the function of actin II in the parasite.
Integrated Multi-omics Analyses of NFKB1 patients B cells points towards an up regulation of NF-κB network inhibitors
Authors: Camacho-Ordonez Nadezhda , Ramirez Neftali , Posadas-Cantera Sara , Caballero-Oyteza Andrés , Fliegauf Manfred , Zhao Fangwen , Guarini Maria , Gernedl Victoria , Pecoroaro Mateo , Warnatz Klaus , Bock Christoph , Ballestar Esteban , Geiger Roger , Proietti Michele , Grimbacher Bodo 
Published: November 2022

AbstractThe transcription factor NF-κB plays a pivotal role in the adaptive immune response. Pathogenic variants inNFKB1are the most common genetic etiology of common variable immunodeficiency (CVID). Patients frequently present with impaired terminal B cell differentiation, autoimmunity, and hyperinflammatory immune dysregulation. NF-κB signaling and target gene expression are expected to be dysregulated inNFKB1-mutated patients. Here, we performed a multi-omics characterization of B cells from a cohort of clinically affected and unaffectedNFKB1mutation carriers. Our analysis identified specific epigenetic dysregulation and gene expression differences on B cells fromNFKB1-mutated patients. We observed an aberrant expression of negative regulators of NF-κB signaling inNFKB1mutation carriers, which may be a key factor for the autoinflammatory phenotype of these patients. Moreover, our analysis points towards a dysregulation ofXBP1andBCL3, key players of B cell activation and proliferation at different stages of B cell differentiation. The reduced expression of negative regulators of the NF-κB network is likely to be one of several mechanisms responsible for the aberrant NF-κB signaling, which impairs the maintenance of a normal humoral immune response. In summary, our findings highlight epigenetic and gene expression changes in B cells associated withNFKB1mutations. Our data give insight into future therapeutic opportunities for patients withNFKB1(haplo)insufficiency.