bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomic and Proteomic Stratification of Equine Osteoarthritis
Authors: Anderson James R , Phelan Marie M , Caamaño-Gutiérrez Eva , Clegg Peter D , Rubio-Martinez Luis M , Peffers Mandy J 
Published: May 2020

AbstractOsteoarthritis (OA) is characterised by loss of articular cartilage, synovial membrane dysfunction and subchondral sclerosis. Few studies have used a global approach to stratify equine synovial fluid (SF) molecular profiles according to OA severity. SF was collected from 58 metacarpophalangeal (MCP) and metatarsophalangeal joints of racing Thoroughbred horses (Hong Kong Jockey Club; HKJC) and 83 MCP joints of mixed breed horses from an abattoir and equine hospital (biobank). Joints were histologically and macroscopically assessed for OA severity. For proteomic analysis, native SF and SF loaded onto ProteoMiner™ equalisation columns, to deplete high abundant proteins, were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification. Validation of selected differentially expressed proteins was undertaken using clinical SF collected during diagnostic investigations. Native SF metabolites were analysed using 1D1H Nuclear Magnetic Resonance (NMR). 1,834 proteins and 40 metabolites were identified in equine SF. Afamin levels decreased with synovitis severity and four uncharacterised proteins decreased with OA severity. Gelsolin and lipoprotein binding protein decreased with OA severity and apolipoprotein A1 levels increased for mild and moderate OA. Within the biobank, glutamate levels decreased with OA severity and for the HKJC cohort, 2-aminobutyrate, alanine and creatine increased with severity. Proteomic and metabolomic integration was undertaken using linear regression via Lasso penalisation modelling, incorporating 29 variables (R2=0.82) with principal component 2 able to discriminate advanced OA from earlier stages, predominantly driven by H9GZQ9, F6ZR63 and alanine. Combining biobank and HKJC datasets, discriminant analysis of principal components modelling prediction was good for mild OA (90%). This study has stratified equine OA using both metabolomic and proteomic SF profiles and identified a panel of markers of interest which may be applicable to grading OA severity. This is also the first study to undertake computational integration of NMR metabolomic and LC-MS/MS proteomic datasets of any biological system.
Planarian stem cells sense the identity of missing tissues to launch targeted regeneration
Authors: Bohr Tisha E. , Shiroor Divya A. , Adler Carolyn E. 
Published: May 2020

SummaryIn order to regenerate tissues successfully, stem cells must first detect injuries and then produce missing cell types through largely unknown mechanisms. Planarian flatworms have an extensive stem cell population responsible for regenerating any organ after amputation. Here, we compare stem cell responses to different injuries by amputation of a single organ, the pharynx, or removal of tissues from other organs by decapitation. We find that planarian stem cells adopt distinct behaviors depending on what tissue is missing: loss of non-pharyngeal tissues increases numbers of non-pharyngeal progenitors, while removal of the pharynx specifically triggers proliferation and expansion of pharynx progenitors. By pharmacologically inhibiting either proliferation or activation of the MAP kinase ERK, we identify a narrow window of time during which proliferation, followed by ERK signaling, produces pharynx progenitors necessary for regeneration. Further, unlike pharynx regeneration, eye regeneration does not depend on proliferation or ERK activation. These results indicate that stem cells tailor their proliferation and expansion to match the regenerative needs of the animal.
SARS-CoV-2 codon usage bias downregulates host expressed genes with similar codon usage
Authors: Alonso Andres Mariano , Diambra Luis 
Published: May 2020

ABSTRACTSevere acute respiratory syndrome is quickly spreading throughout the world and was declared as a pandemic by the World Health Organisation (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral proteins synthesis and its relationship with the proteins synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could conduct to an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes, and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis contributes to understand some deleterious collateral effect as result of the viral replication. In this manner, our finding contribute to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.
Neutralization of SARS-CoV-2 by destruction of the prefusion Spike
Authors: Huo Jiandong , Zhao Yuguang , Ren Jingshan , Zhou Daming , Duyvesteyn Helen ME , Ginn Helen M , Carrique Loic , Malinauskas Tomas , Ruza Reinis R , Shah Pranav NM , Tan Tiong Kit , Rijal Pramila , Coombes Naomi , Bewley Kevin , Radecke Julika , Paterson Neil G , Supasa Piyasa , Mongkolsapaya Juthathip , Screaton Gavin R , Carroll Miles , Townsend Alain , Fry Elizabeth E , Owens Raymond J , Stuart David I 
Published: May 2020

SummaryThere are as yet no licenced therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric Spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2 (ACE2), initiating conformational changes that drive membrane fusion. We find that monoclonal antibody CR3022 binds the RBD tightly, neutralising SARS-CoV-2 and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding would facilitate conversion to the fusion-incompetent post-fusion state. Cryo-EM analysis confirms that incubation of Spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope may be useful therapeutically, possibly in synergy with an antibody blocking receptor attachment.HighlightsCR3022 neutralises SARS-CoV-2Neutralisation is by destroying the prefusion SPIKE conformationThis antibody may have therapeutic potential alone or with one blocking receptor attachment
Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain
Authors: Bernardi Austen , Huang Yihan , Harris Bradley , Xiong Yongao , Nandi Somen , McDonald Karen A. , Faller Roland 
Published: May 2020

AbstractWe develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor. Additionally, we optimize algorithms for protein glycosylation modelling in order to expedite future model development. All models and algorithms are openly available.
Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure
Authors: Chand Gyanendra Bahadur , Banerjee Atanu , Azad Gajendra Kumar 
Published: May 2020

ABSTRACTThe rapid development of SARS-CoV-2 mediated COVID-19 pandemic has been the cause of significant health concern, highlighting the immediate need for the effective antivirals. SARS-CoV-2 is an RNA virus that has an inherent high mutation rate. These mutations drive viral evolution and genome variability, thereby, facilitating viruses to have rapid antigenic shifting to evade host immunity and to develop drug resistance. Viral RNA-dependent RNA polymerases (RdRp) perform viral genome duplication and RNA synthesis. Therefore, we compared the available RdRp sequences of SARS-CoV-2 from Indian isolates and ‘Wuhan wet sea food market virus’ sequence to identify, if any, variation between them. We report seven mutations observed in Indian SARS-CoV-2 isolates and three unique mutations that showed changes in the secondary structure of the RdRp protein at region of mutation. We also studied molecular dynamics using normal mode analyses and found that these mutations alter the stability of RdRp protein. Therefore, we propose that RdRp mutations in Indian SARS-CoV-2 isolates might have functional consequences that can interfere with RdRp targeting pharmacological agents.
Effects of regulatory network organization and environment on PmrD connector activity and polymyxin resistance inKlebsiella pneumoniaeandEscherichia coli
Authors: Chen Annie I. , Zhu Jun , Goulian Mark 
Published: May 2020

AbstractPolymyxins are a class of cyclic peptides with antimicrobial activity against Gram-negative bacteria. Resistance to these compounds is often mediated by pathways that also confer resistance to host antimicrobial peptides. InEnterobacteriaceae, the PhoQ/PhoP and PmrB/PmrA two-component systems regulate many of the genes associated with these resistance mechanisms. InK. pneumoniae, spontaneous polymyxin resistance is frequently acquired through inactivation of the genemgrB, which encodes a negative regulator of PhoQ. However, this resistance mechanism has not been reported in other genera ofEnterobacteriaceae, despite the presence ofmgrBamong many members of this family. In addition, the frequency of developing spontaneous resistance to the antimicrobial peptide polymyxin through chromosomal mutations is much higher inKlebsiellacompared toSalmonellaorE. coli. Here we show that inK. pneumoniae, PmrD is not required for polymyxin resistance arising from inactivation ofmgrB. In addition, we show that inE. coli, the protein PmrD can activate PmrA under certain conditions. Our results suggest that the importance of PmrD connector activity in polymyxin resistance depends on both the network organization and on the environmental conditions associated with PmrB stimulation.
Co-evolution of Eukaryotic-like Vps4 and ESCRT-III Subunits in the Asgard Archaea
Authors: Lu Zhongyi , Fu Ting , Li Tianyi , Liu Yang , Zhang Siyu , Li Jinquan , Dai Junbiao , Koonin Eugene V , Li Guohui , Chu Huiying , Li Meng 
Published: May 2020

ABSTRACTThe emergence of the endomembrane system is a key step in the evolution of cellular complexity during eukaryogenesis. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery is essential and required for the endomembrane system functions in eukaryotic cells. Recently, genes encoding eukaryote-like ESCRT protein components have been identified in the genomes of Asgard archaea, a newly proposed archaeal superphylum that is thought to include the closest extant prokaryotic relatives of eukaryotes. However, structural and functional features of Asgard ESCRT remain uncharacterized. Here we show that Vps4, Vps2/24/46, and Vps20/32/60, the core functional components of the Asgard ESCRT, co-evolved eukaryote-like structural and functional features. Phylogenetic analysis shows that Asgard Vps4, Vps2/24/46, and Vps20/32/60 are closely related to their eukaryotic counterparts. Molecular dynamic simulation and biochemical assays indicate that Asgard Vps4 contains a eukaryote-like Microtubule Interacting and Transport (MIT) domain that binds the distinct type-1 MIT Interacting Motif and type-2 MIT Interacting Motif in Vps2/24/46, and Vps20/32/60, respectively. The Asgard Vps4 partly, but much more efficiently than homologs from other archaea, complements thevps4null mutant ofSaccharomyces cerevisiae, further supporting the functional similarity between the membrane remodeling machineries of Asgard archaea and eukaryotes. Thus, this work provides evidence that the ESCRT complexes from Asgard archaea and eukaryotes are evolutionarily related and functionally similar. Thus, despite the apparent absence of endomembranes in Asgard archaea, the eukaryotic ESCRT seems to have been directly inherited from an Asgard ancestor, to become a key component of the emerging endomembrane system.IMPORTANCEThe discovery of Asgard archaea has changed the exiting ideas on the origins of Eukaryotes. Researchers propose that eukaryotic cells evolve from Asgard archaea. This hypothesis partly stems from the presence of multiple eukaryotic signature proteins in Asgard archaea, including homologues of ESCRT proteins that are essential components of the endomembrane system in eukaryotes. However, structural and functional features of Asgard ESCRT remain unknown. Our study provides evidence that Asgard ESCRT is functionally comparable to the eukaryotic counterparts suggesting that, despite the apparent absence of endomembranes in archaea, eukaryotic ESCRT was inherited from an Asgard archaeal ancestor, alongside the emergence of endomembrane system during eukaryogenesis.
Applying Lexical Link Analysis to Discover Insights from Public Information on COVID-19
Authors: Zhao Ying , Zhou Charles C. 
Published: May 2020

SARS-Cov-2, the deadly and novel virus, which has caused a worldwide pandemic and drastic loss of human lives and economic activities. An open data set called the COVID-19 Open Research Dataset or CORD-19 contains large set full text scientific literature on SARS-CoV-2. The Next Strain consists of a database of SARS-CoV-2 viral genomes from since 12/3/2019. We applied an unique information mining method named lexical link analysis (LLA) to answer the call to action and help the science community answer high-priority scientific questions related to SARS-CoV-2. We first text-mined the CORD-19. We also data-mined the next strain database. Finally, we linked two databases. The linked databases and information can be used to discover the insights and help the research community to address high-priority questions related to the SARS-CoV-2’s genetics, tests, and prevention.Significance StatementIn this paper, we show how to apply an unique information mining method lexical link analysis (LLA) to link unstructured (CORD-19) and structured (Next Strain) data sets to relevant publications, integrate text and data mining into a single platform to discover the insights that can be visualized, and validated to answer the high-priority questions of genetics, incubation, treatment, symptoms, and prevention of COVID-19.
Synthetic Zippers as an Enabling Tool for Engineering of Non-Ribosomal Peptide Synthetases
Authors: Bozhueyuek Kenan A. J. , Watzel Jonas , Abbood Nadya , Bode Helge B. 
Published: May 2020

AbstractNon-ribosomal peptide synthetases (NRPSs) are the origin of a wide range of natural products, including many clinically used drugs. Engineering of these often giant biosynthetic machineries to produce novel non-ribosomal peptides (NRPs) at high titre is an ongoing challenge. Here we describe a strategy to functionally combine NRPS fragments of Gram-negative and -positive origin, synthesising novel peptides at titres up to 290 mg l-1. Extending from the recently introduced definition of eXchangeUnits (XUs), we inserted synthetic zippers (SZs) to split single protein NRPSs into up to three independently expressed and translated polypeptide chains. These synthetic type of NRPS (type S) enables easier access to engineering, overcomes cloning limitations, and provides a simple and rapid approach to building peptide libraries via the combination of different NRPS subunits.One Sentence SummaryDivide and Conquer: A molecular tool kit to reprogram the biosynthesis of non-ribosomal peptides.
Roles of developmentally regulated KIF2A alternative isoforms in cortical neuron migration and differentiation
Authors: Akkaya Cansu , Atak Dila , Kamacioglu Altug , Akarlar Busra Aytul , Guner Gokhan , Bayam Efil , Taskin Ali Cihan , Ozlu Nurhan , Ince-Dunn Gulayse 
Published: May 2020

AbstractKIF2A is a microtubule-depolymerizing kinesin motor protein with essential roles in neural progenitor division and axonal pruning during brain development. KIF2A is alternatively spliced in nervous tissue by specific RNA-binding proteins. However, how different KIF2A isoforms function during development of the cerebral cortex is not known. Here, we focus on threeKif2aisoforms expressed in mouse embryonic and postnatal cerebral cortex. We show that KIF2A is essential for dendritic pruning of primary cortical neurons in mice and that the functions of all three isoforms are sufficient for this process. Interestingly, only two of the isoforms can sustain radial migration of cortical neurons while a third isoform, lacking a key stretch of twenty amino acids, is ineffective. By proximity-labeling-based interactome mapping for individual KIF2A isoforms, we provide novel insight into how isoform specific interactions can confer changes to KIF2A protein function. Our interactome mapping identifies previously known KIF2A interactors, proteins localized to the mitotic spindle poles, and unexpectedly, also translation factors, ribonucleoproteins and proteins that are targeted to the mitochondria and ER, suggesting a novel transport function for KIF2A.
Optimization of crankpin bearing lubrication under dynamic loading considering effect of micro asperity contact
Authors: Nguyen Vanliem , Wu Zhenpeng , Le Vanquynh 
Published: May 2020

Purpose
To improve the lubrication and tribology performance (LTP) of the crankpin bearing, this paper aims to propose the optimization of the crankpin bearing parameters considering effect of the high-speed dynamic load and micro asperity contact.

Design/methodology/approach
A numerical simulation method combined by the slider-crank-mechanism dynamic and lubrication models is applied to solve the dynamic and lubrication equations of crankpin bearing. These equations are then computed via an algorithm program written in Matlab software. The contact force (Wac) in the asperity contact region, friction force (Ff) and friction coefficient (μ) of crankpin bearing are chosen as objective functions. The original parameters and experimental data of the engine are used for the simulation to enhance the reliability of the research results. The parameters are then optimized to obtain the minimum values of Wac, Ff and μ.

Findings
The research results show that the LTP is significantly improved with optimized parameters. Particularly, the maximum values of Wac and Ff are greatly decreased by 27 and 32%, respectively.

Originality/value
Reducing the width, radius and surface roughness and increasing the radial clearance of crankpin bearing can improve better the LTP.

Peer review
The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-02-2020-0072/
An integrated framework for prioritizing the outsourcing performance outcomes
Authors: Prajapati Himanshu , Kant Ravi , Tripathi Sandeep Mani 
Published: May 2020

Purpose
Outsourcing is a crucial tool for an organization to focus on its core business operations. The purpose of this study is to find critical success factors (CSFs) of outsourcing and to prioritize the performance outcomes of outsourcing because of the adoption of its CSFs.

Design/methodology/approach
This research proposes the hybrid framework of fuzzy Delphi, fuzzy analytic hierarchy process (F-AHP) and fuzzy additive ratio assessment (F-ARAS) to fulfill the research objectives. Fuzzy Delphi is used to finalize the CSFs of outsourcing and F-AHP provides the relative weights to it. F-ARAS is used to prioritize the outsourcing performance indicators with respect to CSFs. The empirical case investigation of three Indian large-scale public sector process industries is conducted to demonstrate the applicability of the proposed framework.

Findings
The result shows that increased dominance in core activity, ability to increase or decrease capacity, improved financial performance, optimized resource utilization and increased market share are the top five performance outcomes because of the adoption of outsourcing CSFs.

Research limitations/implications
Factors such as cultural, political, environmental and size of the organization may have a significant implication on the research results.

Originality/value
This is a novel approach towards the prioritization of performance outcomes of outsourcing. Moreover, the present research is a helpful tool to manage outsourcing and choosing which performance outcome of outsourcing ought to be used to measure implementation. This will help to recognize potential opportunities and preparing strategic planning for both short-term and long-term goals.
Snacking, sugar-sweetened beverage consumption and child obesity in low-income households
Authors: Walsh Christine E. , Seguin-Fowler Rebecca , Ammerman Alice , Hanson Karla , Pitts Jilcott Stephanie B. , Kolodinsky Jane , Sitaker Marilyn , Ennett Susan 
Published: May 2020

Purpose
Snacking contributes to one-quarter of children’s total daily energy intake in the USA, with many snack foods being nutrient-poor and energy-dense. Snacking and sugary beverage consumption have been identified as potential contributors to childhood overweight and obesity and may play a particularly important role among children from socioeconomically disadvantaged households that generally display higher rates of obesity. This exploratory study investigated associations between consumption of snack foods, sugar-sweetened beverages (SSB) and overweight and obesity in children from low-income households.

Design/methodology/approach
Data from households that participated in a multi-state cost-offset (CO-CSA) community supported agriculture intervention in 2016 and 2017 (n = 305) were analyzed. Fixed effect regression models were used to estimate associations between child monthly consumption of salty snack foods; sweet snack foods and SSBs; and child weight status, accounting for demographic characteristics.

Findings
No associations were found between snack or SSB consumption and child overweight. However, household income was significantly, negatively related to all three consumption variables (Salty snacks: ß = −0.09, SE = 0.04, p = 0.02; Sweet snacks: ß= −0.10, SE = 0.04, p = 0.01; SSB: ß= −0.21, SE = 0.05, p = 0.0001). The results suggest that household income may play an important role in children’s snacking and SSB behaviors among more disadvantaged households.

Practical implications
Factors beyond snack food and SSB consumption should be explored to better understand childhood overweight and obesity, and to inform future obesity interventions.

Originality/value
Socioeconomic disparities in childhood obesity are an ongoing policy-relevant issue within the USA and internationally. This study provides new information about child snacking behaviors in a unique, low-income population and contributes to the evidence base regarding the role household context in shaping child consumption behaviors.