bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Critical Determinants of ACE2-RBD Interaction
Authors: Brown Emily E. F. , Rezaei Reza , Jamieson Taylor , Dave Jaahnavi , Martin Nikolas T. , Singaravelu Ragunath , Crupi Mathieu J.F. , Boulton Stephen , Tucker Sarah , Duong Jessie , Poutou Joanna , Pelin Adrian , Yasavoli-Sharahi Hamed , Taha Zaid , Arulanandam Rozanne , Surendran Abera , Ghahremani Mina , Austin Bradley , Matar Chantal , Diallo Jean-Simon , Bell John C. , Ilkow Carolina S. , Azad Taha 
Published: January 2021

AbstractDespite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. Utilizing our recently developed NanoBiT technology-based biosensor, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, before and after the addition of competitive inhibitors, as well as neutralizing antibody activity. These critical determinants of virus-host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.
Comparative genomics reveals factors associated with phenotypic expression ofWolbachia
Authors: Baião Guilherme Costa , Janice Jessin , Galinou Maria , Klasson Lisa 
Published: January 2021

ABSTRACTWolbachiais a widespread, vertically transmitted bacterial endosymbiont known for manipulating arthropod reproduction. Its most common form of reproductive manipulation is Cytoplasmic incompatibility (CI), observed when a modification in the male sperm leads to embryonic lethality unless a compatible rescue factor is present in the female egg. CI attracts scientific attention due to its implications for host speciation and in the use ofWolbachiafor controlling vector-borne diseases. However, our understanding of CI is complicated by the complexity of the phenotype, whose expression depends on both symbiont and host factors. In the present study, we perform a comparative analysis of nine completeWolbachiagenomes with known CI properties in the same genetic host background,Drosophila simulansSTC. We describe genetic differences between closely related strains and uncover evidence that phages and other mobile elements contribute to rapid evolution of both genomes and phenotypes ofWolbachia. Additionally, we identify both known and novel genes associated with the modification and rescue functions of CI. We combine our observations with published phenotypic information and discuss how variability incifgenes, novel CI-associated genes andWolbachiatiter might contribute to poorly understood aspects of CI such as strength and bidirectional incompatibility. We speculate that high titer CI strains could be better at invading new hosts already infected with a CIWolbachia, due to a higher rescue potential, and suggest that titer might thus be a relevant parameter to consider for future strategies using CIWolbachiain biological control.
The SON RNA splicing factor is required for intracellular trafficking that promotes centriole assembly
Authors: Stemm-Wolf Alexander J. , O’Toole Eileen T. , Sheridan Ryan M. , Morgan Jacob T. , Pearson Chad G. 
Published: January 2021

AbstractControl of centrosome assembly is critical for cell division, intracellular trafficking and cilia. Regulation of centrosome number occurs through the precise duplication of centrioles that reside in centrosomes. Here we explored transcriptional control of centriole assembly and find that the RNA splicing factor SON is specifically required for completing procentriole assembly. Whole genome mRNA sequencing identified genes whose splicing and expression are affected by the reduction of SON, with an enrichment in genes involved in the microtubule cytoskeleton, centrosome and centriolar satellites. SON is required for the proper splicing and expression ofCEP131which encodes a major centriolar satellite protein and is required to organize the trafficking and microtubule network around the centrosomes. This study highlights the importance of the distinct microtubule trafficking network that is intimately associated with nascent centrioles and is responsible for procentriole development.
A thermodynamic model for water activity and redox potential in evolution and development
Authors: Dick Jeffrey M. 
Published: January 2021

AbstractReactions involving water and oxygen are basic features of geological and biological processes. To understand how life interacts with its environment requires monitoring interactions with H2O and O2 at timescales relevant to not only organismal growth but also billions of years of geobiological evolution. Here, chemical transformations intrinsic to evolution and development were characterized by analyzing data from recent phylostratigraphic and proteomic studies. This two-stage analysis involves obtaining chemical metrics (carbon oxidation state and stoichiometric hydration state) from the elemental compositions of proteins followed by modeling the relative stabilities of target proteins against a proteomic background to infer thermodynamic parameters (oxygen fugacity, water activity, and virtual redox potential (Eh)). The main results of this study are a rise in carbon oxidation state of proteins spanning the time of the Great Oxidation Event, a rise in virtual redox potential that coincides with the likely emergence of aerobic metabolism, a rise in carbon oxidation state of proteins inferred from the transcriptome in late stages of Bacillus subtilis biofilm growth, and a drop in stoichiometric hydration state of the fruit fly developmental proteome at the same time as a drop in organismal water content. Stoichiometric hydration state also decreases for proteins with more recent gene ages and through stages of biofilm development, leading to predictions of higher hydration potentials at earlier time points. By building chemical representations of protein evolution and developmental proteomes, exciting new types of geobiochemical proxies can be developed.
RGI-GOLVEN signalling promotes FLS2 abundance to regulate plant immunity
Authors: Stegmann Martin , Zecua-Ramirez Patricia , Ludwig Christina , Lee Ho-Seok , Peterson Brenda , Nimchuk Zachary L. , Belkhadir Youssef , Hückelhoven Ralph 
Published: January 2021

AbstractEndogenous plant signalling peptides regulate developmental and growth-related processes. Recent research indicates that some of these peptides are classified as phytocytokines as they have regulatory functions during plant immune responses. However, the mechanistic basis for phytocytokine-mediated immune modulation remains largely elusive. Here, we identify GOLVEN2 (GLV2) peptides as novel phytocytokines inArabidopsis thaliana. By peptide application, precursor overexpression and loss-of-function studies we show that GLV2 enhances sensitivity of plants to elicitation with the bacterial flagellin epitope flg22. GLV2 is perceived by ROOT MERISTEM GROWTH FACTOR 1 INSENSITIVE (RGI) receptors and RGI3 forms an flg22-induced complex with the flg22-receptor FLAGELLIN SENSITIVE 2, suggesting that RGIs are part of activated pattern recognition receptor signalling platforms. GLV2 perception increases posttranscriptional FLS2 abundance and RGIs promote FLS2 protein accumulation. Thus, GLV-RGI signalling controls above ground plant immunity via a novel mechanism of phytocytokine activity.
Genomic evolution of epitopes and Low Complexity Regions in Plasmodium
Authors: Medley Sarah N. , Beaudet Alyssa , Piontkivska Helen , Battistuzzi Fabia U. 
Published: January 2021

AbstractDespite decades-long efforts to eradicate malaria, pathogens genomic complexity and variability continue to pose major challenges for the vaccine and drug development. Here we examined the evolutionary history of epitopes and epitope-like regions to determine whether they share underlying evolutionary mechanisms and potential functions that are relevant to pathogens interactions with the host immune response. Our comparative sequence analyses contrasted patterns of sequence conservation, amino acid composition, and protein structure of epitopes and low complexity regions (LCRs) in 21 Plasmodium species. Our results revealed many similarities in amino acid composition and preferred secondary structures between epitopes and LCRs; however, we also identified differences in evolutionary trends where LCRs exhibit overall lower sequence conservation and higher disorder. We also found that both epitopes and LCRs have a wide array of configurations, with various levels of sequence conservation and structural order. We propose that such combination of different levels of conservation and structural order between epitopes and LCRs in the same gene play a role in maintaining the functional integrity required by the pathogen along with the variability necessary to evade the host immune response, with LCRs playing a role in the evasion particularly in the vicinity of conserved epitopes. Overall, our results suggest that there are at least two categories of LCRs, where some LCRs play a potential protective role for conserved (ordered) epitopes because of their variable (or disordered) sequence, while others are less disordered and are as conserved as epitopes. The former ones may be an evolutionary necessity for Plasmodium to maintain the diversity of epitopes, while the latter category may serve currently unknown function(s) and deserve to be examined in greater detail. Our findings show that there may be many more candidate targets for future anti-malarial treatments than initially thought and that some of these targets may work across strains and species.
Mitophagy antagonism by Zika virus reveals Ajuba as a regulator of PINK1-Parkin signaling, PKR-dependent inflammation, and viral invasion of tissues
Authors: Ponia Sanket S. , Robertson Shelly J. , McNally Kristin L. , Sturdevant Gail L. , Lewis Matthew , Jessop Forrest , Bosio Catherine M. , Kendall Catherine , Gallegos Dylan , Hay Arielle , Schwartz Cindi , Rosenke Rebecca , Saturday Greg , Martens Craig , Best Sonja M. 
Published: January 2021

ABSTRACTDysregulated inflammation dominated by chemokine expression is a key feature of disease following infection with the globally important human pathogens, Zika virus (ZIKV) and dengue virus, but a mechanistic understanding of how pro-inflammatory responses are initiated is lacking. Mitophagy is a quality control mechanism that regulates innate immune signaling and cytokine production through selective degradation of damaged mitochondria. Here, we demonstrate that ZIKV NS5 antagonizes mitophagy by binding to the host protein Ajuba and preventing its translocation to depolarized mitochondria where it is required for PINK1 activation and downstream signaling. Consequent mitophagy suppression amplified the production of pro-inflammatory chemokines through PKR sensing of mitochondrial RNA. In Ajuba−/−mice, ZIKV induced early expression of pro-inflammatory chemokines associated with significantly enhanced dissemination to tissues. This work identifies Ajuba as a critical regulator of mitophagy, and demonstrates a role for mitophagy in limiting systemic inflammation following infection by globally important human viruses.
ZCCHC8 is required for the degradation of pervasive transcripts originating from multiple genomic regulatory features
Authors: Collins Joshua W. , Martin Daniel ,   Genomics and Computational Biology Core, Wang Shaohe , Yamada Kenneth M. 
Published: January 2021

ABSTRACTThe vast majority of mammalian genomes are transcribed as non-coding RNA in what is referred to as “pervasive transcription.” Recent studies have uncovered various families of non-coding RNA transcribed upstream of transcription start sites. In particular, highly unstable promoter upstream transcripts known as PROMPTs have been shown to be targeted for exosomal degradation by the nuclear exosome targeting complex (NEXT) consisting of the RNA helicase MTR4, the zinc-knuckle scaffold ZCCHC8, and the RNA binding protein RBM7. Here, we report that in addition to its known RNA substrates, ZCCHC8 is required for the targeted degradation of pervasive transcripts produced at CTCF binding sites, open chromatin regions, promoters, promoter flanking regions, and transcription factor binding sites. Additionally, we report that a significant number of RIKEN cDNAs and predicted genes display the hallmarks of PROMPTs and are also substrates for ZCCHC8 and/or NEXT complex regulation suggesting these are unlikely to be functional genes. Our results suggest that ZCCHC8 and/or the NEXT complex may play a larger role in the global regulation of pervasive transcription than previously reported.
Styles of mesoscale brittle deformations associated with the Miocene folding of the Taishu Group, Tsushima, between the Japan Sea and East China Sea backarc basins
Authors: Yamaji Atsushi , Yanagisawa Tatsuhiko , Sato Katsushi 
Published: February 2021

AbstractThe Taishu Group is a folded, Eocene–Lower Miocene, thick sedimentary package exposed widely on Tsushima Island between the Japan Sea and East China Sea. This location makes the strata important to understand tectonics and paleo‐environments in the Far East, but the timing of the folding is controversial. We studied the styles of brittle deformations of the strata. It was found that flextural‐slip folds were dominant. Mesoscale faults were classified into two groups: NE–SW trending reverse faults and NW–SE trending strike‐slip faults. Members of both the groups showed movements largely perpendicular to the fold axes. The latter group consisted of sinistral and dextral faults. Accordingly, we interpreted that they were transfer faults activated during the folding. Consequently, mesoscale faults and flexural‐slip faults evidence the map‐scale plane strain of the Taishu Group in the plane perpendicular to the NE‐trending fold axes. There were few transpressional deformations in the group. This is inconsistent with the transpression hypothesis for explaining the simultaneous folding and Japan Sea opening. Another hypothesis in which the folds in Tsushima are regarded as an onshore part of the Taiwan‐Shinji fold belt is inconsistent with the timing of folding suggested by mining geologists to be consistent with and contemporaneous with this deformation. On the other hand, we found that dolerite dikes and sills were involved in the folding. Therefore, we conclude that the folding began during the late Early Miocene time and climaxed during the ore mineralization at around 15 Ma. We suggest that the folding in Tsushima was the easternmost manifestation of the compressional regime around the Yellow Sea and East China Sea in the Early to early Middle Miocene, and that the compression was brought about by the arrival of the Philippine Sea plate to initiate buoyant subduction under Kyushu.
Adapting to supply‐and‐demand emerging trends for antigen‐negative red blood cell units
Authors: Trépanier Patrick , Chevrier Marie‐Claire , Constanzo Yanez Jessica , Baillargeon Nadia , St‐Pierre Christine , Perreault Josée 
Published: January 2021

AbstractBackgroundA global downtrend in blood usage has been observed by many countries, while the demand for antigen‐negative red blood cell (RBC) units used in antigen‐matched transfusions keeps increasing. The declining number of units collected exposes blood providers to a rapidly evolving supply challenge.MethodsThis study was conducted retrospectively with use of internal data analysis to weigh Québec's situation regarding global and antigen‐negative RBC demand, to measure the effects of community‐directed recruitment and blood drives, and to evaluate the benefits of mass‐scale RBC genotyping.ResultsOur findings confirm a global RBC usage downtrend of over 20% total in the past 10 years with a steady antigen‐negative usage and highlight the most requested negative antigen combinations. Our data also show our +39.5% progress regarding the number of Black donors recruited for antigen matching of patients with sickle cell disease in the past 3 years, as well as a constantly growing number of just‐in‐time blood collection for complex orders. Finally, our data summarize the efficiency of our mass‐scale RBC genotyping efforts.ConclusionAltogether, this study confirms the demand trends for regular and antigen‐negative RBC units in Québec and the efficient effects of our recruitment and typing strategies.
A High Resolution Simulation of a Single Shock-Accelerated Particle
Authors: Maxon W. Curtis , Nielsen Tanner , Denissen Nicholas , Regele Jonathan D. , McFarland Jacob 
Published: January 2021

Abstract
Particle drag models, which capture macroviscous and pressure effects, have been developed over the years for various flow regimes to enable cost effective simulations of particle-laden flows. The relatively recent derivation by Maxey and Riley has provided an exact equation of motion for spherical particles in a flow field based on the continuum assumption. Many models that have been simplified from these equations have provided reasonable approximations; however, the sensitivity of particle-laden flows to particle drag requires a very accurate model to simulate. To develop such a model, a two-dimensional axisymmetric Navier–Stokes direct numerical simulation of a single particle in a transient, shock-driven flow field was conducted using the hydrocode FLAG. FLAGs capability to run arbitrary Lagrangian-Eulerian hydrodynamics coupled with solid mechanic models makes it an ideal code to capture the physics of the flow field around and in the particle as it is shock-accelerated—a challenging regime to study. The goal of this work is twofold: to provide a validation for FLAGs Navier–Stokes and heat diffusion solutions and to provide a rationale for recent experimental particle drag measurements.
Universality-breaking effects in $$e^+e^-$$ hadronic production processes
Authors: Boglione M. , Simonelli A. 
Published: January 2021

AbstractRecent BELLE measurements provide the cross section for single hadron production in $$e^+e^-$$

e
+

e
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annihilations, differential in thrust and in the hadron transverse momentum with respect to the thrust axis. Universality breaking effects due to process-dependent soft factors make it very difficult to relate this cross sections to those corresponding to hadron-pair production in $$e^+e^-$$

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+

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annihilations, where transverse momentum dependent (TMD) factorization can be applied. The correspondence between these two cross sections is examined in the framework of the Collins-Soper-Sterman factorization, in the collinear as well as in the TMD approach. We propose a scheme that allows to relate the TMD parton densities defined in 1-hadron and in 2-hadron processes, neatly separating, within the soft and collinear parts, the non-perturbative terms from the contributions that can be calculated perturbatively. The regularization of rapidity divergences introduces cut-offs, the arbitrariness of which will be properly reabsorbed by means of a mechanism closely reminiscent of a gauge transformation. In this way, we restore the possibility to perform global phenomenological studies of TMD physics, simultaneously analyzing data belonging to different hadron classes.
Strong CP and solitonic axions resonant from Higgs’ cusp-kinks radiative corrections
Authors: Maalouf Hani W. 
Published: January 2021

A limiting algebraic resonance seems to recuperate the pseudo-scalar Higgs from the simultaneous breaking process. On an energy kernel consideration, an imposed nonharmonic boundary exclusion provides a basis for the scaling (proved derived from the conformal classes) of its extending as radiative correction diagrams, plus whose anomalies eliminate upon reaching geometrically a type of steep power as linked to, completely from the curvature. A CP violating form, then shows after the appearance of both a parity, plus a polarization defiance, together with the Higgs decoupled to the favor of the equivalence class for a scalar coupling, leading to the types of allowed UV fixed points, with the possible fading of some of its parametric resonances (tachyon) by quantum corrections, into then the estimation of consecutive QCD and fuzzy axion masses by taking into account that their interaction (dimensional) operators such which have the completeness, both of metric and/or gauge types, being so then, first with KSVZ (showing as being resonant along with sterile neutrinos) and DFS types or second with creation of an axion soliton. The fit into the phenomenological constraints is also checked.
Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma–Induced Osteolysis and Reduces Overall Survival
Authors: Lo Chen Hao , Shay Gemma , McGuire Jeremy J. , Li Tao , Shain Kenneth H. , Choi Jun Yong , Fuerst Rita , Roush William R. , Knapinska Anna M. , Fields Gregg B. , Lynch Conor C. 
Published: February 2021

AbstractMultiple myeloma promotes systemic skeletal bone disease that greatly contributes to patient morbidity. Resorption of type I collagen–rich bone matrix by activated osteoclasts results in the release of sequestered growth factors that can drive progression of the disease. Matrix metalloproteinase-13 (MMP13) is a collagenase expressed predominantly in the skeleton by mesenchymal stromal cells (MSC) and MSC-derived osteoblasts. Histochemical analysis of human multiple myeloma specimens also demonstrated that MMP13 largely localizes to the stromal compartment compared with CD138+ myeloma cells. In this study, we further identified that multiple myeloma induces MMP13 expression in bone stromal cells. Because of its ability to degrade type I collagen, we examined whether bone stromal–derived MMP13 contributed to myeloma progression. Multiple myeloma cells were inoculated into wild-type or MMP13–null mice. In independent in vivo studies, MMP13–null mice demonstrated significantly higher overall survival rates and lower levels of bone destruction compared with wild-type controls. Unexpectedly, no differences in type I collagen processing between the groups were observed. Ex vivo stromal coculture assays showed reduced formation and activity in MMP13–null osteoclasts. Analysis of soluble factors from wild-type and MMP13–null MSCs revealed decreased bioavailability of various osteoclastogenic factors including CXCL7. CXCL7 was identified as a novel MMP13 substrate and regulator of osteoclastogenesis. Underscoring the importance of host MMP13 catalytic activity in multiple myeloma progression, we demonstrate the in vivo efficacy of a novel and highly selective MMP13 inhibitor that provides a translational opportunity for the treatment of this incurable disease.Significance:Genetic and pharmacologic approaches show that bone stromal–derived MMP13 catalytic activity is critical for osteoclastogenesis, bone destruction, and disease progression.