bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of warming temperatures on coregonine embryogenesis within and among species
Authors: Stewart Taylor R. , Mäkinen Mikko , Goulon Chloé , Guillard Jean , Marjomäki Timo J. , Lasne Emilien , Karjalainen Juha , Stockwell Jason D. 
Published: February 2021

ABSTRACTThe greatest known global response of lakes to climate change has been an increase in water temperatures. The responses of many lake fishes to warming water temperatures are projected to be inadequate to counter the speed and magnitude of climate change. We experimentally evaluated the responses of embryos from a group of cold, stenothermic fishes (Salmonidae Coregoninae) to increased incubation temperatures. Study groups included cisco (Coregonus artedi) from lakes Superior and Ontario (USA), and vendace (C. albula) and European whitefish (C. lavaretus) from Lake Southern Konnevesi (Finland). Embryos from artificial crossings were incubated at water temperatures of 2.0, 4.5, 7.0, and 9.0°C, and their responses were quantified for developmental and morphological traits. Embryo survival, incubation period, and length-at- hatch were inversely related to incubation temperature whereas yolk-sac volume increased with incubation temperature within study groups. However, varying magnitudes of responses among study groups suggested differential levels of developmental plasticity to climate change. Differential levels of parental effects indicate genetic diversity may enable all study groups to adapt to cope with some degree of changing environmental conditions. Our results suggest that the coregonines sampled within and among systems may have a wide range of embryo responses to warming incubation conditions.
Systematic beach monitoring as a health assessment tool: cetacean morbillivirus under non-epizootic circumstances in stranded dolphins
Authors: Marutani Victor H. B. , Miyabe Flávia , Alfieri Alice F. , Domit Camila , de Matos Andressa M. R. N. , Filho Mário R. C. M. , Bracarense Ana P. F. R. L. 
Published: February 2021

AbstractCetacean morbillivirus (CeMV) was identified as the etiologic agent of several epizootic episodes worldwide. Most of these studies are based on unusual mortality events or identification of new viral strains. We investigated the occurrence of CeMV under non-epizootic circumstances at a world heritage in Southern Brazil by a combination of pathologic, immunohistochemical and molecular assays. From 325 stranded cetaceans, 40 were included. Guiana dolphin (Sotalia guianensis) was the species most frequent. Interstitial pneumonia and non-suppurative encephalitis were the main pathologic findings associated to CeMV infection. Intracytoplasmic immunolabeling anti-CeMV was observed mainly in lungs and lymph nodes. All samples were negative in RT-PCR assay. Diagnosis of CeMV is challenging in areas where epizootic episodes have not been recorded and due topostmortemchanges. We observed a CeMV prevalence of 27.5%. The results described here increase the knowledge about CeMV under non-epizootic conditions in Brazil.Article Summary LineWe observed a prevalence of 27.5% of CeMV in a World Heritage site of Paraná’s coast. The results indicate an increase in the prevalence of CeMV at this region and, possibly, a degradation of marine ecosystem. Marine mammals are sentinels of marine environment and the ocean health is inextricably linked to human health on a global scale.
StrainGE: A toolkit to track and characterize low-abundance strains in complex microbial communities
Authors: van Dijk Lucas R. , Walker Bruce J. , Straub Timothy J. , Worby Colin J. , Grote Alexandra , Schreiber Henry L. , Anyansi Christine , Pickering Amy J. , Hultgren Scott J. , Manson Abigail L. , Abeel Thomas , Earl Ashlee M. 
Published: February 2021

AbstractHuman-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify nearest known references and find variants for multiple conspecific strains within a sample at relative abundances below 0.1% in typical metagenomic datasets.
Structure of an infectious mammalian prion
Authors: Kraus Allison , Hoyt Forrest , Schwartz Cindi L. , Hansen Bryan , Hughson Andrew G. , Artikis Efrosini , Race Brent , Caughey Byron 
Published: February 2021

ABSTRACTClassical mammalian prions are assemblies of prion protein molecules that are extraordinarily transmissible, with a microgram of protein containing up to 108lethal doses of infectivity1,2. Unlike most other pathologic and amyloidogenic proteins, prions typically contain glycolipid anchors3and abundant asparagine‐linked glycans4‐6. The infectious nature, complexity, and biophysical properties of prions have complicated structural analyses and stymied any prior elucidation of 3D conformation at the polypeptide backbone level7. Here we have determined the structure of the core of a fully infectious, brain‐derived prion by cryo‐electron microscopy with ∼3.1 Å resolution. The purified prions are amyloid fibrils comprised of monomers assembled with parallel in‐register intermolecular beta sheets and connecting chains. Residues ∼95‐227 of each monomer provide one rung of the ordered fibril core, with the glycans and glycolipid anchor projecting from the lateral surfaces of the fibril. The fibril ends, where prion growth occurs, are formed by single monomers in an extended serpentine combination of β‐ arches, a Greek key, and loops that presumably template the refolding of incoming monomers. Our results describe an atomic model to underpin detailed molecular hypotheses of how pathologic prion proteins can propagate as infectious agents, and how such propagation and associated pathogenesis might be impeded.
In vitroefficacy of Artemisia extracts against SARS-CoV-2
Authors: Nie Chuanxiong , Trimpert Jakob , Moon Sooyeon , Haag Rainer , Gilmore Kerry , Kaufer Benedikt B. , Seeberger Peter H. 
Published: February 2021

AbstractTraditional medicines based on herbal extracts have been proposed as affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Teas and drinks containing extracts ofArtemisia annuaandArtemisia afrahave been widely used in Africa in efforts to prevent and fight COVID-19 infections. We sought to study the ability of differentA. annuaandA. afraextracts and the Covid-Organics drink produced in Madagascar to inhibit SARS-CoV-2 and feline coronavirus (FCoV) replicationin vitro.Several extracts as well as Covid-Organics inhibit SARS-CoV-2 and FCoV replication at concentrations that did not affect cell viability. It remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral replication following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment in patients.
Antisense oligonucleotide-based drug development for Cystic Fibrosis patients carrying the 3849+10kb C-to-T splicing mutation
Authors: Oren Yifat S. , Sinai Michal Irony-Tur , Golec Anita , Barchad-Avitzur Ofra , Mutyam Venkateshwar , Li Yao , Hong Jeong , Ozeri-Galai Efrat , Hatton Aurélie , Reiter Joel , Sorscher Eric J. , Wilton Steve D. , Kerem Eitan , Rowe Steven M. , Sermet-Gaudelus Isabelle , Kerem Batsheva 
Published: February 2021

AbstractAntisense oligonucleotide (ASO)-based drugs for splicing modulation were recently been approved for various genetic diseases with unmet need. Here we aimed to develop an ASO-based splicing modulation therapy for Cystic Fibrosis (CF) patients carrying the 3849+10kb C-to-T splicing mutation in the CFTR gene. We have screened, in FRT cells expressing this mutation, ~30 ASOs chemically modified with 2′-O-Methyl on a phosphrothioate backbone, targeted to prevent the recognition and inclusion of a cryptic exon generated due to the mutation. The screening identified five ASO candidates able to promote CFTR correct splicing and rescue channel activity. Further analyses in well differentiated primary human nasal and bronchial epithelial cells (HNEs, HBEs), derived from patients carrying at least one 3849+10kb C-to-T allele, led to the identification of a highly potent lead ASO. The ASO was efficiently delivered by free uptake into patients’ HNEs and HBEs and completely restored CFTR function to wild type levels in cells from a homozygous patient and led to 43±8% of wild type levels in cells from various heterozygous patients. Optimized efficiency was further obtained with 2’-Methoxy Ethyl chemical modification. The results demonstrate the therapeutic potential and clinical benefit of ASO-based splicing modulation for genetic diseases caused by splicing mutations.
Subcellular dynamics studies reveal how tissue-specific distribution patterns of iron are established in developing wheat grains
Authors: Sheraz Sadia , Wan Yongfang , Venter Eudri , Verma Shailender K , Xiong Qing , Waites Joshua , Connorton James M , Shewry Peter R , Moore Katie L , Balk Janneke 
Published: February 2021

AbstractUnderstanding iron trafficking in plants is key to enhancing the nutritional quality of crops. Due to the difficulty of imaging iron in transit, little is known about iron translocation and distribution in developing seeds. A novel approach, combining57Fe isotope labelling and NanoSIMS, was used to visualize iron translocation dynamics at the subcellular level in wheat grain,Triticum aestivumL. We were able to track the main route of iron from maternal tissues to the embryo through different cell types. Further evidence for this route was provided by genetically diverting iron into storage vacuoles, as confirmed by histological staining and TEM-EDS. Virtually all iron was found in intracellular bodies, indicating symplastic rather than apoplastic transport. Aleurone cells contained a new type of iron body, highly enriched in57Fe, and most likely represents iron-nicotianamine being delivered to phytate globoids. Correlation with tissue-specific gene expression provides an updated model of iron homeostasis in cereal grains with relevance for future biofortification efforts.
SUMOylation of the chromodomain factor MRG-1 inC. elegansaffects chromatin-regulatory dynamics
Authors: Baytek Gülkiz , Blume Alexander , Demirel Funda Gerceker , Bulut Selman , Mertins Philipp , Tursun Baris 
Published: February 2021

AbstractEpigenetic mechanisms to control chromatin accessibility and structure is important for gene expression in eukaryotic cells. Chromatin regulation ensures proper development and cell fate specification but is also essential later in life. Modifications of histone proteins as an integral component of chromatin can promote either gene expression or repression, respectively. Proteins containing specific domains such as the chromodomain recognize mono-, di- or tri-methylated lysine residues on histone H3. The chromodomain protein MRG-1 inCaenorhabditis elegansis the ortholog of mammalian MRG15, which belongs to theMORF4RelatedGene (MRG) family in humans. InC. elegansMRG-1 predominantly binds methylated histone H3 lysine residues at position 36 (H3K36me3). MRG-1 is important during germline maturation and for safeguarding the germ cell identity. However, it lacks enzymatic activity and depends on protein-protein interaction to cooperate with other factors to regulate chromatin. To elucidate the variety of MRG-1 interaction partners we performed in-depth protein-protein interaction analysis using immunoprecipitations coupled with mass-spectrometry. Besides previously described and novel interactions with other proteins, we also detected a strong association with the Small Ubiquitin-like Modifier (SUMO). Since SUMO is known to be attached to proteins in order to modulate the target proteins activity we assessed whether MRG-1 is post-translationally modified by SUMOylation. Notably, we provide evidence that MRG-1 is indeed SUMOylated and that this post-translational modification influences the chromatin-binding profile of MRG-1 in theC. elegansgenome. Our presented study hints towards an important role of SUMOylation in the context of epigenetic regulation via the chromodomain protein MRG-1, which may be a conserved phenomenon also in mammalian species.
CRISPR/Cas9 targeting of MCPyV T antigen in Merkel tumors
Authors: Arora Reety , Gupta Komal , Vijaykumar Anjali 
Published: February 2021

ABSTRACTMerkel cell carcinoma (MCC) is a rare, aggressive skin cancer caused either by Merkel cell polyomavirus (MCPyV) T antigen gene expression, post integration (∼80% cases), or by UV mediated DNA damage. Viral-positive Merkel tumors are not only caused by but also oncogenically addicted to tumor antigen expression. In this study we used CRISPR-Cas9 based gene-editing to develop a potential therapeutic tool for MCPyV positive MCC. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas system is a genome editing technology whereby a guide RNA (gRNA) molecule, targets a Cas endonuclease to a specific genomic site, using sequence homology, and induces a double strand break. To target MCPyV T antigens, we designed a strategy using 2 gRNAs targeting the T antigen genomic region that would cut off a substantial portion of the gene thereby rendering it dysfunctional. We validated the MCPYV T antigen targeting efficiency of our gRNAs, both individually and together byin vitrocleavage assays. Finally, to translate this finding, we delivered this CRISPR system in patient-derived MCC cell lines and show reduction in T antigen gene expression. Our proof-of-concept study shows that 2 MCPyV targeting CRISPR/Cas gRNAs in combination can knock out MCPyV T antigen, thus, being of therapeutic importance. We hope that this CRISPR system can be potentially deliveredin vivofor advancing MCPyV positive MCC treatment in the future.
Close to optimal cell sensing ensures the robustness of tissue differentiation process: the avian photoreceptor mosaic case
Authors: Barua Arnab , Beygi Alireza , Hatzikirou Haralampos 
Published: February 2021

AbstractThe way that progenitor cell fate decisions and the associated environmental sensing are regulated to ensure the robustness of the spatial and temporal order in which cells are generated towards a fully differentiating tissue still remains elusive. Here, we investigate how cells regulate their sensing intensity and radius to guarantee the required thermodynamic robustness of a differentiated tissue. In particular, we are interested in finding the conditions where dedifferentiation at cell level is possible (microscopic reversibility) but tissue maintains its spatial order and differentiation integrity (macroscopic irreversibility). In order to tackle this, we exploit the recently postulated Least microEnvironmental Uncertainty Principle (LEUP) to develop a theory of stochastic thermodynamics for cell differentiation. To assess the predictive and explanatory power of our theory, we challenge it against the avian photoreceptor mosaic data. By calibrating a single parameter, the LEUP can predict the cone color spatial distribution in the avian retina and, at the same time, suggest that such a spatial pattern is associated with quasi-optimal cell sensing. By means of the stochastic thermodynamics formalism, we find out that thermodynamic robustness of differentiated tissues depends on cell metabolism and cell sensing properties. In turn, we calculate the limits of the cell sensing radius that ensure the robustness of differentiated tissue spatial order. Finally, we further constrain our model predictions to the avian photoreceptor mosaic.
Fast and Accurate Distance-based Phylogenetic Placement using Divide and Conquer
Authors: Balaban Metin , Jiang Yueyu , Roush Daniel , Zhu Qiyun , Mirarab Siavash 
Published: February 2021

AbstractPhylogenetic placement of query samples on an existing phylogeny is increasingly used in molecular ecology, including sample identification and microbiome environmental sampling. As the size of available reference trees used in these analyses continues to grow, there is a growing need for methods that place sequences on ultra-large trees with high accuracy. Distance-based placement methods have recently emerged as a path to provide such scalability while allowing flexibility to analyze both assembled and unassembled environmental samples. In this paper, we introduce a distance-based phylogenetic placement method, APPLES-2, that is more accurate and scalable than existing distance-based methods and even some of the leading maximum likelihood methods. This scalability is owed to a divide-and-conquer technique that limits distance calculation and phylogenetic placement to parts of the tree most relevant to each query. The increased scalability and accuracy enables us to study the effectiveness of APPLES-2 for placing microbial genomes on a data set of 10,575 microbial species using subsets of 381 marker genes. APPLES-2 has very high accuracy in this setting, placing 97% of query genomes within three branches of the optimal position in the species tree using 50 marker genes. Our proof of concept results show that APPLES-2 can quickly place metagenomic scaffolds on ultra-large backbone trees with high accuracy as long as a scaffold includes tens of marker genes. These results pave the path for a more scalable and widespread use of distance-based placement in various areas of molecular ecology.
ExpandingN-Glycopeptide Identifications by Fragmentation Prediction and Glycome Network Smoothing
Authors: Klein Joshua , Carvalho Luis , Zaia Joseph 
Published: February 2021

AbstractAccurate glycopeptide identification in mass spectrometry-based glycoproteomics is a challenging problem at scale. Recent innovation has been made in increasing the scope and accuracy of glycopeptide identifications, with more precise uncertainty estimates for each part of the structure. We present a layered approach to glycopeptide fragmentation modeling that improvesN-glycopeptide identification in samples without compromising identification quality, and a site-specific method to increase the depth of the glycoproteome confidently identifiable even further. We demonstrate our techniques on a pair of previously published datasets, showing the performance gains at each stage of optimization, as well as its flexibility in glycome definition and search space complexity. These techniques are provided in the open-source glycomics and glycoproteomics platform GlycReSoft available athttps://github.com/mobiusklein/glycresoft.
Multisite phosphorylation by Cdk1 initiates delayed negative feedback to control mitotic transcription
Authors: Asfaha Jonathan B. , Örd Mihkel , Carlson Christopher R. , Faustova Ilona , Loog Mart , Morgan David O. 
Published: February 2021

SummaryCell-cycle progression is driven by the phosphorylation of cyclin-dependent kinase (Cdk) substrates1–3. The order of substrate phosphorylation depends in part on the general rise in Cdk activity during the cell cycle4–7, together with variations in substrate docking to sites on associated cyclin and Cks subunits3, 6, 8–10. Many substrates are modified at multiple sites to provide more complex regulation9, 11–14. Here, we describe an elegant regulatory circuit based on multisite phosphorylation of Ndd1, a transcriptional co-activator of genes required for mitotic progression15, 16. As cells enter mitosis, Ndd1 phosphorylation by Cdk1 is known to promote mitotic cyclin (CLB2) gene transcription, resulting in positive feedback17–20. Consistent with these findings, we show that low Cdk1 activity promotesCLB2expression at mitotic entry. We also find, however, thatCLB2expression is inhibited by high levels of Cdk1 activity in a mitotic arrest. Inhibition is accompanied by Ndd1 degradation, and we present evidence that high mitotic Cdk1-Clb2 activity generates phosphodegrons on Ndd1, leading to its degradation. Complete Ndd1 phosphorylation by the Clb2-Cdk1-Cks1 complex requires the phosphothreonine-binding site of Cks1, as well as a novel phosphate-binding pocket on the cyclin Clb221. We therefore propose that initial phosphorylation by Cdk1 primes the protein for secondary phosphorylation at phosphodegrons, resulting in degradation only at high Cdk1 activity. Together, our results suggest that rising levels of mitotic Cdk1 activity act at multiple phosphorylation sites on Ndd1, first triggering rapid positive feedback and then promoting delayed negative feedback, resulting in a pulse of mitotic gene expression.
Dynamin-2 controls complement receptor 3- mediated phagocytosis completion and closure
Authors: Mularski Anna , Wimmer Ryszard , Arbaretaz Floriane , Le Goff Gabriel , Niedergang Florence 
Published: February 2021

AbstractPhagocytosis is the mechanism of the internalization of large particles, microorganisms and cellular debris. The complement pathway represents one of the first mechanisms of defense against infection and the complement receptor 3 (CR3), which is highly expressed on macrophages, is a major receptor for many pathogens and debris. Key to dissecting the mechanisms by which CR3-mediated phagocytosis occurs, is understanding how the complex actin binding protein machinery and associated regulators interact with actin during phagocytosis, from triggering of receptor, through to phagosome formation and closure. However, how CR3-mediated phagosome completion and closure are orchestrated is not known. Here, we reveal that dynamin-2 is recruited concomitantly with polymerised actin at the site of the nascent phagosomes and accumulates until membrane scission. Inhibition of dynamin activity leads to stalled phagocytic cups and a decrease in the amount of F-actin at the site of phagocytosis. Acute inhibition of dynamin activity in living phagocytosing cells established that dynamin-2 plays a critical role in the effective scission of the CR3-phagosome from the plasma membrane. Thus, dynamin-2 has two distinct roles in CR3-mediated phagocytosis, in the assembly of the F-actin phagocytic cup and during phagosome scission.