bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical phenotyping and staging of brain tumors
Authors: Akeret Kevin , Vasella Flavio , Staartjes Victor E. , Velz Julia , Müller Timothy , Neidert Marian Christoph , Weller Michael , Regli Luca , Serra Carlo , Krayenbühl Niklaus 
Published: March 2021

AbstractIn contrast to most other tumors, the anatomical extent of brain tumors is not objectified and quantified through staging. Staging systems are built on the understanding of the anatomical sequence of tumor progression and its relation to histopathological dedifferentiation and survival. While major advances in the understanding of primary brain tumors at a histological, cellular and molecular level have been achieved in recent decades, our understanding at a macroscopic anatomical level is limited. The aim of this study was to describe the anatomical phenotype of the most frequent brain tumor entities based on topographic probability and growth behavior analysis. The association of anatomical tumor features with survival probability was assessed and a prototypical staging system for WHO grade II-IV glioma was proposed based on the hypothesized anatomical sequence of tumor progression. The analysis is based on data from a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumor. On preoperative MRI, the relative tumor density (RTD) of different topographic, phylogenetic and ontogenetic parcellation units was derived through normalization of the relative tumor prevalence to the relative volume of the respective structure. While primary central nervous system lymphoma (PCNSL) showed a high RTD along white matter tracts, the RTD in metastases was highest along terminal arterial flow areas. Neuroepithelial tumors (NT) demonstrated a high and homogeneous RTD along all sectors of the ventriculo-cortical axis, avoiding adjacent units, consistent with a transpallial behavior within phylo-ontogenetic radial units. Additionally, the topographic probability in NT correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. The anatomical tumor growth behavior was analyzed by comparing pre- and postoperative MRI, showing that a ventriculofugal growth dominates in NT. With progressive histopathological dedifferentiation of NT, a gradual deviation from this neuroepithelial anatomical behavior was found. By comparing survival probability, we identified prognostically critical steps in the anatomical behavior of NT. Based on a hypothesized sequence of anatomical tumor progression, we developed a three-level prototypical staging system for WHO grade II-IV glioma. This staging system proved to be accurate across histological, molecular, radiomorphological and clinical strata based on Kaplan Meier curves and multivariable survival analysis. Similar to staging systems for other tumors, a staging system such as this one may have the potential to inform stage-adapted treatment decisions.
Monitoring the rise of the SARS-CoV-2 lineage B.1.1.7 in Tenerife (Spain) since mid-December 2020
Authors: Alcoba-Florez Julia , Lorenzo-Salazar Jose M. , Gil-Campesino Helena , Íñigo-Campos Antonio , de Artola Diego García-Martínez , García-Olivares Victor , Díez-Gil Oscar , Valenzuela-Fernández Agustín , Ciuffeda Laura , González-Montelongo Rafaela , Flores Carlos 
Published: March 2021

AbstractStarting in December 2020, a sharp increase of COVID-19 cases occurred in Tenerife compared to the rest of the Canary Islands (Spain). Because of the direct touristic connections between Tenerife and the UK, and the rapid transmission and dominance of the SARS-CoV-2 B.1.1.7 variant of concern (VOC-202012/01) by the end of November 2020 in South England, here we measured the proportion of B.1.1.7 cases occurring between the 18th of December 2020 and the 25th of February 2021. Out of the 2,091 COVID-19 positive nasopharyngeal swab samples assessed, 226 showed a spike gene target failure (SGTF). Subsequent viral genome sequencing further confirmed that 93.2% of them corresponded to the B.1.1.7 lineage. Furthermore, a rapid increase in the proportion of SGTF variants was detected in up to 10.7% of positive cases during the Christmas season despite stricter measures for containing the transmission were imposed in Tenerife in the period. These results support the local transmission of SARS-CoV-2 B.1.1.7 lineage in Tenerife since late December 2020 although it is not yet dominant.
Rootstocks influence the response of ripening grape berries to leafroll associated viruses
Authors: Vondras Amanda M. , Lerno Larry , Massonnet Mélanie , Minio Andrea , Rowhani Adib , Liang Dingren , Garcia Jadran , Quiroz Daniela , Figueroa-Balderas Rosa , Golino Deborah A. , Ebeler Susan E. , Al Rwahnih Maher , Cantu Dario 
Published: March 2021

AbstractGrapevine leafroll-associated virus (GLRaV) infections are accompanied by symptoms with varying severity. Using a dedicated experimental vineyard, we studied the responses to GLRaVs in ripening berries from Cabernet franc grapevines grafted to different rootstocks and with zero, one, or pairs of leafroll infection(s). RNA sequencing data were mapped to a high-quality Cabernet franc genome reference assembled to carry out this study and integrated with hormone and metabolite abundance data. This study identified several molecular levers that participate in responses to GLRaVs, including those that are condition-dependent. This included describing common responses to GLRaVs that were reproduced in two consecutive years, in plants grafted to different rootstocks, and in more than one infection condition. Though different infections were inconsistently distinguishable from one another overall, the effects of infections in plants grafted to different rootstocks were distinct at each developmental stage. Conserved responses included the modulation of pathogen detecting genes, increases in abscisic acid signaling and cytoskeleton remodeling gene expression. The abundance of abscisic acid (ABA), related metabolites, ABA and hormone signaling-related gene expression, and the expression of several transcription factor families differentiated rootstocks overall. These data show that rootstock influences the effect of GLRaVs in ripening berries.
A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission
Authors: Yang Zhenke , Shi Yang , Cui Huiting , Yang Shuzhen , Gao Han , Yuan Jing 
Published: March 2021

AbstractMosquito midgut epithelium traversal is an essential component of transmission of malaria parasites. Phospholipid flippases are eukaryotic type IV ATPases (P4-ATPases), which in association with CDC50 cofactors, translocate phospholipids across lipid bilayers to maintain the membrane asymmetry. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasiteP. yoelii. Disruption of ATP7 results in block of parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are motile and capable of invading the midgut, they are quickly eliminated within the epithelial cells by a process that is independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase co-factor CDC50C. Importantly, depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to translocate phosphatidylcholine (PC) across the plasma membrane, resulting in PC exposure at the ookinete surface. Lastly, ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifiesPlasmodiumflippase as a novel mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.
A free-living protist that lacks canonical eukaryotic DNA replication and segregation systems
Authors: Salas-Leiva Dayana E. , Tromer Eelco C. , Curtis Bruce A. , Jerlström-Hultqvist Jon , Kolisko Martin , Yi Zhenzhen , Salas-Leiva Joan S. , Gallot-Lavallée Lucie , Kops Geert J. P. L. , Archibald John M. , Simpson Alastair G. B. , Roger Andrew J. 
Published: March 2021

AbstractCells must replicate and segregate their DNA with precision. In eukaryotes, these processes are part of a regulated cell-cycle that begins at S-phase with the replication of DNA and ends after M-phase. Previous studies showed that these processes were present in the last eukaryotic common ancestor and the core parts of their molecular systems are conserved across eukaryotic diversity. However, some unicellular parasites, such as the metamonadGiardia intestinalis, have secondarily lost components of the DNA processing and segregation apparatuses. To clarify the evolutionary history of these systems in these unusual eukaryotes, we generated a high-quality draft genome assembly for the free-living metamonadCarpediemonas membraniferaand carried out a comparative genomics analysis. We found that parasitic and free-living metamonads harbor a conspicuously incomplete set of canonical proteins for processing and segregating DNA. Unexpectedly,Carpediemonasspecies are further streamlined, lacking the origin recognition complex, Cdc6 and other replisome components, most structural kinetochore subunits including the Ndc80 complex, as well as several canonical cell-cycle checkpoint proteins.Carpediemonasis the first eukaryote known to have lost this large suite of conserved complexes, suggesting that it has a highly unusual cell cycle and that unlike any other known eukaryote, it must rely on novel or alternative set of mechanisms to carry out these fundamental processes.
Comparative immunogenicity of bacterially expressed soluble trimers and nanoparticle displayed influenza hemagglutinin stem immunogens
Authors: Kar Uddipan , Khaleeq Sara , Garg Priyanka , Bhat Madhuraj , Reddy Poorvi , Vignesh Venkada Subramanian , Upadhyaya Aditya , Das Mili , Chakshusmathi Ghadiyaram , Pandey Suman , Dutta Somnath , Varadarajan Raghavan 
Published: March 2021

AbstractCurrent influenza vaccines need to be updated annually due to mutations in the globular head of the viral surface protein, hemagglutinin (HA). To address this, vaccine candidates have been designed based on the relatively conserved HA stem domain and have shown protective efficacy in animal models. Oligomerization of the antigens either by fusion to oligomerization motifs or display on self-assembling nanoparticle scaffolds, can induce more potent immune responses compared to the corresponding monomeric antigen due to multivalent engagement of B-cells. Since nanoparticle display can increase manufacturing complexity, and often involves one or more mammalian cell expressed components, it is important to characterize and compare various display and oligomerization scaffolds. Using a structure guided approach, we successfully displayed multiple copies of a previously designed soluble, trimeric influenza stem domain immunogen, pH1HA10, on the ferritin like protein, MsDps2 (12 copies), Ferritin (24 copies) and Encapsulin (180 copies). All proteins were expressed inEscherichia coli. The nanoparticle fusion immunogens were found to be well folded and bound to the influenza stem directed broadly neutralizing antibodies with high affinity. An 8.5 Å Cryo-EM map of Msdps2-pH1HA10 confirmed the successful design of the nanoparticle fusion immunogen. Mice immunization studies with the soluble trimeric stem and nanoparticle fusion constructs revealed that all of them were immunogenic, and protected mice against homologous (A/Belgium/145-MA/2009) and heterologous (A/Puerto Rico/8/1934) challenge with 10MLD50mouse adapted virus. Although nanoparticle display conferred a small but statistically significant improvement in protection relative to the soluble trimer in a homologous challenge, heterologous protection was similar in both nanoparticle-stem immunized and trimeric stem immunized groups. Such rapidly producible, bacterially expressed antigens and nanoparticle scaffolds are useful modalities to tackle future influenza pandemics.
Hülle-cell-mediated protection of fungal reproductive and overwintering structures against fungivorous animals
Authors: Liu Li , Dirnberger Benedict , Valerius Oliver , Fekete-Szücs Enikő , Harting Rebekka , Sasse Christoph , Nordzieke Daniela E. , Pöggeler Stefanie , Karlovsky Petr , Gerke Jennifer , Braus Gerhard H. 
Published: March 2021

AbstractFungal Hülle cells with nuclear storage and developmental backup functions are reminiscent of multipotent stem cells. In the soil, Hülle cells nurse the overwintering fruiting bodies ofAspergillus nidulans. The genome ofA. nidulansharbors genes for the biosynthesis of xanthones. We show that enzymes and metabolites of this biosynthetic pathway accumulate in Hülle cells under the control of the regulatory velvet complex, which coordinates development and secondary metabolism. Deletion strains blocked in the conversion of anthraquinones to xanthones are delayed in maturation and growth of fruiting bodies. Xanthones are not required for sexual development but exert antifeedant effects on fungivorous animals such as springtails and woodlice. These findings reveal a novel role of Hülle cells in establishing secure niches forA. nidulansby accumulating metabolites with antifeedant activity that protect reproductive structures from animal predators.
Community Evaluation of Glycoproteomics Informatics Solutions Reveals High-Performance Search Strategies of SerumN- andO-Glycopeptide Data
Authors: Kawahara Rebeca , Chernykh Anastasia , Alagesan Kathirvel , Bern Marshall , Cao Weiqian , Chalkley Robert J. , Cheng Kai , Choo Matthew S. , Edwards Nathan , Goldman Radoslav , Hoffmann Marcus , Hu Yingwei , Huang Yifan , Kim Jin Young , Kletter Doron , Liquet-Weiland Benoit , Liu Mingqi , Mechref Yehia , Meng Bo , Neelamegham Sriram , Nguyen-Khuong Terry , Nilsson Jonas , Pap Adam , Park Gun Wook , Parker Benjamin L. , Pegg Cassandra L. , Penninger Josef M. , Phung Toan K. , Pioch Markus , Rapp Erdmann , Sakalli Enes , Sanda Miloslav , Schulz Benjamin L. , Scott Nichollas E. , Sofronov Georgy , Stadlmann Johannes , Vakhrushev Sergey Y. , Woo Christina M. , Wu Hung-Yi , Yang Pengyuan , Ying Wantao , Zhang Hui , Zhang Yong , Zhao Jingfu , Zaia Joseph , Haslam Stuart M. , Palmisano Giuseppe , Yoo Jong Shin , Larson Göran , Khoo Kai-Hooi , Medzihradszky Katalin F. , Kolarich Daniel , Packer Nicolle H. , Thaysen-Andersen Morten 
Published: March 2021

AbstractGlycoproteome profiling (glycoproteomics) is a powerful yet analytically challenging research tool. The complex tandem mass spectra generated from glycopeptide mixtures require sophisticated analysis pipelines for structural determination. Diverse software aiding the process have appeared, but their relative performance remains untested. Conducted through the HUPO Human Proteome Project – Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates the performance of informatics solutions for system-wide glycopeptide analysis. Mass spectrometry-based glycoproteomics datasets from human serum were shared with all teams. The relative team performance forN- andO-glycopeptide data analysis was comprehensively established and validated through orthogonal performance tests. Excitingly, several high-performance glycoproteomics informatics solutions were identified. While the study illustrated that significant informatics challenges remain, as indicated by a high discordance between annotated glycopeptides, lists of high-confidence (consensus) glycopeptides were compiled from the standardised team reports. Deep analysis of the performance data revealed key performance-associated search variables and led to recommendations for improved “high coverage” and “high accuracy” glycoproteomics search strategies. This study concludes that diverse software for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies, and specifies key variables that may guide future software developments and assist informatics decision-making in glycoproteomics.
RNA-Binding Proteins Direct Myogenic Cell Fate Decisions
Authors: Wheeler Joshua R. , Whitney Oscar N. , Vogler Thomas O. , Nguyen Eric D. , Pawlikowski Bradley , Lester Evan , Cutler Alicia , Elston Tiffany , Betta Nicole Dalla , Parker Kevin R. , Yost Kathryn E. , Vogel Hannes , Rando Thomas A. , Chang Howard Y. , Johnson Aaron M. , Parker Roy , Olwin Bradley B. 
Published: March 2021

ABSTRACTRNA-binding proteins (RBPs) are essential for skeletal muscle regeneration and RBP dysfunction causes muscle degeneration and neuromuscular disease. How ubiquitously expressed RBPs orchestrate complex tissue regeneration and direct cell fate decisions in skeletal muscle remains poorly understood. Single cell RNA-sequencing of regenerating skeletal muscle reveals that RBP expression, including numerous neuromuscular disease-associated RBPs, is temporally regulated in skeletal muscle stem cells and correlates to stages of myogenic differentiation. By combining machine learning with RBP engagement scoring, we discover that the neuromuscular disease associated RBP Hnrnpa2b1 is a differentiation-specifying regulator of myogenesis controlling myogenic cell fate transitions during terminal differentiation. The timing of RBP expression specifies cell fate transitions by providing a layer of post-transcriptional regulation needed to coordinate stem cell fate decisions during complex tissue regeneration.
Natural variants with 2D correlation genetics identify domains coordinating sarcomere proteins during contraction
Authors: Burghardt Thomas P. 
Published: March 2021

AbstractMuscle proteins assemble in a sarcomere then by coordinated action produce contraction force to shorten muscle. In the human heart ventriculum, cardiac myosin motor (βmys) repetitively converts ATP free energy into work. Cardiac myosin binding protein C (MYBPC3) in complex with βmys regulates contraction power generation. Their bimolecular complex βmys/MYBPC3 models the contractile system and is used here to study protein coupling. The database for single nucleotide variants (SNVs) in βmys and MYBPC3 surveys human populations worldwide. It consistently records SNV physical characteristics including substituted residue location in the protein functional domain, the side chain substitution, substitution frequency, and human population group, but inconsistently records SNV implicated phenotype and pathology outcomes. A selected consistent subset of the data trains and validates a feed-forward neural network modeling the contraction mechanism. The full database is completed using the model then interpreted probabilistically with a discrete Bayes network to give the SNV probability for a functional domain location given pathogenicity and human population. Co-domains, intra-protein domains coupling βmys and MYBPC3, are identified by their population correlated SNV probability product for given pathogenicity. Divergent genetics in human populations identify co-domain correlates in this method called 2D correlation genetics. Pathogenic and benign SNV data identify three critical regulatory sites, two in MYBPC3 with links to several domains across the βmys motor, and, one in βmys with links to the known MYBPC3 regulatory domain. Critical sites in MYBPC3 are hinges (one known another proposed) sterically enabling regulatory interactions with βmys. The critical site in βmys is the actin binding C-loop, a contact sensor triggering actin-activated myosin ATPase and contraction velocity modulator coordinating also with actin bound tropomyosin. C-loop and MYBPC3 regulatory domain linkage potentially impacts multiple functions across the contractile system. Identification of co-domains in a binary protein complex implies a capacity to estimate spatial proximity constraints for specific dynamic protein interactions in vivo opening another avenue for protein complex structure/function determination.
Phagocytic “teeth” and myosin-II “jaw” power target constriction during phagocytosis
Authors: Vorselen Daan , Barger Sarah R. , Wang Yifan , Cai Wei , Theriot Julie A. , Gauthier Nils C. , Krendel Mira 
Published: March 2021

AbstractPhagocytosis requires rapid actin reorganization and spatially controlled force generation to ingest targets ranging from pathogens to apoptotic cells. How actomyosin activity directs membrane extensions to engulf such diverse targets remains unclear. Here, we combine lattice light-sheet microscopy (LLSM) with microparticle traction force microscopy (MP-TFM) to quantify actin dynamics and subcellular forces during macrophage phagocytosis. We show that spatially localized forces leading to target constriction are prominent during phagocytosis of antibody-opsonized targets. This constriction is largely mediated by Arp2/3-mediated assembly of discrete actin protrusions containing myosin 1e and 1f (“teeth”) that are interconnected in a ring-like organization. Contractile myosin-II activity contributes to late-stage phagocytic force generation and progression, suggesting a specific role in phagocytic cup closure. Observations of partial target eating attempts and sudden target release via a popping mechanism suggest that constriction may be critical for resolving complexin vivotarget encounters. Overall, our findings suggest a phagocytic cup-shaping mechanism that is distinct from cytoskeletal remodeling in 2D cell motility and may contribute to mechanosensing and phagocytic plasticity.