bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perturbation of ACE2 structural ensembles by SARS-CoV-2 spike protein binding
Authors: Uyar Arzu , Dickson Alex 
Published: March 2021

AbstractThe human ACE2 enzyme serves as a critical first recognition point of coronaviruses, including SARS-CoV-2. In particular, the extracellular domain of ACE2 interacts directly with the S1 tailspike protein of the SARS-CoV-2 virion through a broad protein-protein interface. Although this interaction has been characterized by X-ray crystallography and Cryo-EM, these structures do not reveal significant differences in ACE2 structure upon S1 protein binding. In this work, using several all-atom molecular dynamics simulations, we show persistent differences in ACE2 structure upon binding. These differences are determined with the Linear Discriminant Analysis (LDA) machine learning method and validated using independent training and testing datasets, including long trajectories generated by D. E. Shaw Research on the Anton 2 supercomputer. In addition, long trajectories for 78 potent ACE2-binding compounds, also generated by D. E. Shaw Research, were projected onto the LDA classification vector in order to determine whether the ligand-bound ACE2 structures were compatible with S1 protein binding. This allows us to predict which compounds are “apo-like” vs “complex-like”, as well as to pinpoint long-range ligand-induced allosteric changes of ACE2 structure.
Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
Authors: Lai Chih-Yun , To Albert , Wong Teri Ann S. , Lieberman Michael M. , Clements David E. , Senda James T. , Ball Aquena H. , Pessaint Laurent , Andersen Hanne , Donini Oreola , Lehrer Axel T. 
Published: March 2021

ABSTRACTThe speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain and examined its immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HT™adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody titers, and a robust, antigen-specific IFN-γ secreting response from immune splenocytes in outbred mice. Our findings lay the foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.
FAM57B is a modulator of ceramide synthesis that regulates sphingolipid homeostasis and synaptic composition in the developing brain
Authors: Tomasello Danielle L. , Kim Jiyoon L. , Khodour Yara , McCammon Jasmine M. , Mitalipova Maya , Jaenisch Rudolf , Futerman Anthony H. , Sive Hazel 
Published: March 2021

AbstractThe complex 16p11.2 Deletion Syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder and intellectual disability. We demonstrate that 16pdel iPSC differentiated neurons showed augmented local field potential activity and altered ceramide-related lipid species relative to unaffected.FAM57B, a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. InFAM57Bmutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency ofFAM57Bcontributes to changes in neuronal activity and function in 16pdel Syndrome, through a crucial role for the gene in lipid metabolism.
Optimal transport analysis reveals trajectories in steady-state systems
Authors: Zhang Stephen , Afanassiev Anton , Greenstreet Laura , Matsumoto Tetsuya , Schiebinger Geoffrey 
Published: March 2021

AbstractUnderstanding how cells change their identity and behaviour in living systems is an important question in many fields of biology. The problem of inferring cell trajectories from single-cell measurements has been a major topic in the single-cell analysis community, with different methods developed for equilibrium and non-equilibrium systems (e.g. haematopoeisis vs. embryonic development). We show that optimal transport analysis, a technique originally designed for analysing time-courses, may also be applied to infer cellular trajectories from a single snapshot of a population in equilibrium. Therefore optimal transport provides a unified approach to inferring trajectories, applicable to both stationary and non-stationary systems. Our method, StationaryOT, is mathematically motivated in a natural way from the hypothesis of a Waddington’s epigenetic landscape. We implemented StationaryOT as a software package and demonstrate its efficacy when applied to simulated data as well as single-cell data fromArabidopsis thalianaroot development.
Competitive binding of MatP and topoisomerase IV to the MukB dimerization hinge
Authors: Fisher Gemma L. M. , Bolla Jani R. , Rajasekar Karthik V. , Mäkelä Jarno , Baker Rachel , Zhou Man , Prince Josh P. , Stracy Mathew , Robinson Carol V. , Arciszewska Lidia K. , Sherratt David J. 
Published: March 2021

ABSTRACTSMC complexes have ubiquitous roles in chromosome organisation. InEscherichia coli,the interplay between the SMC complex, MukBEF, and matS-bound MatP in the replication termination region, ter, results in depletion of MukBEF from ter, thus promoting chromosome individualisation by directing replichores to separate cell halves. MukBEF also interacts with topoisomerase IV ParC2E2heterotetramers, to direct its chromosomal distribution to mirror that of MukBEF, thereby facilitating coordination between chromosome organisation and decatenation by topoisomerase IV. Here we demonstrate that the MukB dimerization hinge binds ParC and MatP with the same dimer to dimer stoichiometry. MatP and ParC have an overlapping binding interface on the MukB hinge, leading to their mutually exclusive binding. Furthermore, the MukB hinge fails to stably associate withmatS-bound MatP, while MatP mutants deficient inmatSbinding are impaired in MukB hinge binding, demonstrating thatmatscompetes with the hinge for MatP binding. Cells expressing MukBEF complexes containing a mutation in the MukB hinge interface for ParC/MatP binding are deficient in ParC bindingin vivo,despite having a Muk+topoisomerase IV+phenotype. This mutant protein is also impaired in MatP bindingin vitro,and cells expressing this variant exhibit a MukBEF cellular localisation consistent with impaired MatP binding.
The influence of surface roughness and viscosity on micropitting damage
Authors: Li Wei , Lu Liantao 
Published: March 2021

Purpose
This study aims to investigate the influence of surface roughness and viscosity on micropitting and their influence sequence.

Design/methodology/approach
Specimens were made of carburized and quenched 18CrNiMo7-6, and different surface roughness was obtained by grinding and shot peening. Tests were carried out on a rolling-sliding tribometer, with different viscosity lubricants and a heavy load under a boundary lubrication condition. The laser confocal microscope was used to measure the aspects, surface roughness, profiles in the contacted region and micropitting damage percentage. A factorial experiment was designed, and the range analysis was applied to find the sequence of influence of surface roughness and viscosity.

Findings
The result shows that surface roughness has a more noticeable influence since the change of viscosity cannot generate sufficient wear loss to suppress micropitting.

Originality/value
The influence sequence of two factors on micropitting was investigated and the reason for the distribution was analyzed.
HIV supply chains in low- and middle-income countries: overview and research opportunities
Authors: Stulens Sofie , De Boeck Kim , Vandaele Nico 
Published: March 2021

PurposeDespite HIV being reported as one of the major global health issues, availability and accessibility of HIV services and supplies remain limited, especially in low- and middle-income countries. The effective and efficient operation of HIV supply chains is critical to tackle this problem. The purpose of this paper is to give an introduction to HIV supply chains in low- and middle-income countries and identify research opportunities for the operations research/operations management (OR/OM) community.Design/methodology/approachFirst, the authors review a combination of the scientific and grey literature, including both qualitative and quantitative papers, to give an overview of HIV supply chain operations in low- and middle-income countries and the challenges that are faced by organizing such supply chains. The authors then classify and discuss the relevant OR/OM literature based on seven classification criteria: decision level, methodology, type of HIV service modeled, challenges, performance measures, real-life applicability and countries covered. Because research on HIV supply chains in low- and middle-income countries is limited in the OR/OM field, this part also includes papers focusing on HIV supply chain modeling in high-income countries.FindingsThe authors conclude this study by identifying several tendencies and gaps and by proposing future research directions for OR/OM research.Originality/valueTo the best of the authors’ knowledge, this paper is the first literature review addressing this specific topic from an OR/OM perspective.
A study on factors limiting online shopping behaviour of consumers
Authors: Daroch Bindia , Nagrath Gitika , Gupta Ashutosh 
Published: March 2021

Purpose
This study aims to investigate consumer behaviour towards online shopping, which further examines various factors limiting consumers for online shopping behaviour. The purpose of the research was to find out the problems that consumers face during their shopping through online stores.

Design/methodology/approach
A quantitative research method was adopted for this research in which a survey was conducted among the users of online shopping sites.

Findings
As per the results total six factors came out from the study that restrains consumers to buy from online sites – fear of bank transaction and faith, traditional shopping more convenient than online shopping, reputation and services provided, experience, insecurity and insufficient product information and lack of trust.

Research limitations/implications
This study is beneficial for e-tailers involved in e-commerce activities that may be customer-to-customer or customer-to-the business. Managerial implications are suggested for improving marketing strategies for generating consumer trust in online shopping.

Originality/value
In contrast to previous research, this study aims to focus on identifying those factors that restrict consumers from online shopping.
Recipient and donor characteristics govern the hierarchical structure of heterospecific pollen competition networks
Authors: Lanuza Jose B. , Bartomeus Ignasi , Ashman Tia‐Lynn , Bible Greg , Rader Romina 
Published: March 2021

Abstract

Pollinator sharing can have negative consequences for plant fitness via competition for visits as well as with the arrival of heterospecific pollen. Plant traits and relatedness of donor and recipient species have been suggested to drive the observed variation in plant fitness effects of both processes, but how they shape the structure of interspecific pollen competition networks has been overlooked at the community level.

To understand the importance of reproductive traits and relatedness to the impact of heterospecific pollen, we conducted a controlled glasshouse experiment with an artificial co‐flowering community. We performed 2,200 hand pollination crosses by experimentally transferring conspecific pollen alone or with 50% and 100% foreign pollen among 10 species belonging to three different plant families.

Relative to conspecific pollen alone, there was a significant reduction in seed set with 50% heterospecific pollen for 67% of the crosses. This effect is driven largely by recipient traits and the interaction between recipient and donor traits under specific circumstances of trait matching. In general, species with shorter styles, smaller stigmas and lower pollen:ovule ratios were more impacted by heterospecific pollen. These traits and their differences among species led to a hierarchical (or transitive) structure of pollen competition with clear winners and losers. However, phylogenetic distance among recipient and donor species did not explain the effects.

Synthesis. Our study shows that specific traits and trait combinations between donor and recipient species are important in determining seed production outcomes with heterospecific pollen receipt. Moreover, the differences in traits between species lead to a competitive structure with clear ‘winners’ or ‘losers’ species. The results of this study highlight the importance of specific traits in understanding the position of the competitive hierarchy of the species and the mechanisms underlying heterospecific pollen impacts upon plant reproductive success.
Prognostic and comparative performance of cardiovascular risk markers in patients with type 2 diabetes
Authors: Busch Nikolaj , Jensen Magnus T. , Goetze Jens P. , Schou Morten , Biering‐Sørensen Tor , Fritz‐Hansen Thomas , Andersen Henrik U. , Vilsbøll Tina , Rossing Peter , Jørgensen Peter G. 
Published: March 2021

AbstractBackgroundDiagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), high‐sensitivity troponin I (hs‐TnI), and N‐terminal prohormone brain natriuretic peptide (NT‐proBNP) have been suggested as cardiovascular (CV) risk predictors in type 2 diabetes. We studied the separate and combined prognostic yield of these risk markers.MethodsIn all, 1030 patients with type 2 diabetes were recruited from specialized clinics in this prospective cohort study. Full echocardiographic evaluation was feasible in 886 patients in sinus rhythm with adequate image quality. ECG was performed in 998 patients. Albuminuria was measured in 1009 and NT‐proBNP/hs‐TnI in 933 patients. The end point was a composite of CV events.ResultsThe median follow‐up was 4.7 years (interquartile range: 4.0‐5.3), and 174 patients experienced a CV disease event. All considered markers, except hs‐TnI, were significantly (P < .001) associated with the outcome: abnormal echocardiogram (hazard ratio 2.40 [1.70‐3.39]), albuminuria 2.01 (1.47‐2.76), abnormal ECG (2.27 [1.66‐3.08]), high NT‐proBNP (>150 pg/mL) 3.05 (2.11‐4.40), and hs‐TnI 1.12 (0.79‐1.59). After adjusting for clinical variables, all remained significantly associated with the end point. However, after adjusting for each other, only NT‐proBNP >150 pg/mL remained significantly associated with the end point (2.07 [1.28‐3.34], P < .001). Measured by C‐statistics, model performance was highest with log2 (NT‐proBNP) (0.70 [0.65‐0.75]) and similar to clinical variables alone (0.71 [0.67‐0.76]). Combining all risk markers only resulted in a very limited increase in C‐statistics (0.69 [0.64‐0.74]).ConclusionsThis study identified NT‐proBNP over echocardiography, ECG, and albuminuria in risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population.
Construction of a chromosome‐level genome and variation map for the Pacific oyster Crassostrea gigas
Authors: Qi Haigang , Li Li , Zhang Guofan 
Published: March 2021

AbstractThe Pacific oyster (Crassostrea gigas) is a widely distributed marine bivalve of great ecological and economic importance. In this study, we provide a high‐quality chromosome‐level genome assembled using Pacific Bioscience long reads and Hi‐C‐based and linkage‐map‐based scaffolding technologies and a high‐resolution variation map constructed using large‐scale resequencing analysis. The 586.8 Mb genome consists of 10 pseudochromosome sequences ranging from 38.6 to 78.9 Mb, containing 301 contigs with an N50 size of 3.1 Mb. A total of 30,078 protein‐coding genes were predicted, of which 22,757 (75.7%) were high‐reliability annotations supported by a homologous match to a curated protein in the SWISS‐PROT database or transcript expression. Although a medium level of repeat components (57.2%) was detected, the genomic content of the segmental duplications reached 26.2%, which is the highest among the reported genomes. By whole genome resequencing analysis of 495 Pacific oysters, a comprehensive variation map was built, comprised of 4.78 million single nucleotide polymorphisms, 0.60 million short insertions and deletions, and 49,333 copy number variation regions. The structural variations can lead to an average interindividual genomic divergence of 0.21, indicating their crucial role in shaping the Pacific oyster genome diversity. The large amount of mosaic distributed repeat elements, small variations, and copy number variations indicate that the Pacific oyster is a diploid organism with an extremely high genomic complexity at the intra‐ and interindividual level. The genome and variation maps can improve our understanding of oyster genome diversity and enrich the resources for oyster molecular evolution, comparative genomics, and genetic research.
Chromosome level reference of Atlantic halibut Hippoglossushippoglossus provides insight into the evolution of sexual determination systems
Authors: Einfeldt Anthony L. , Kess Tony , Messmer Amber , Duffy Steven , Wringe Brendan F. , Fisher Jonathan , den Heyer Cornelia , Bradbury Ian R. , Ruzzante Daniel E , Bentzen Paul 
Published: March 2021

AbstractChanges in the genetic mechanisms that control sexual determination have occurred independently across the tree of life, and with exceptional frequency in teleost fishes. To investigate the genomic changes underlying the evolution of sexual determination, we sequenced a chromosome‐level genome, multitissue transcriptomes, and reduced representation population data for the Atlantic halibut (Hippoglossus hippoglossus), which has an XY/XX sex determination mechanism and has recently diverged (0.9–3.8 Ma) from the Pacific halibut (Hippoglossus stenolepis), which has a ZZ/ZW system. We used frequency and coverage‐based population approaches to identify a putative sex‐determining factor, GSDF. We characterized regions with elevated heterozygosity and linkage disequilibrium indicating suppression of recombination across a nascent sex chromosome. We detected testis‐specific expression of GSDF, the sequence of which is highly conserved across flatfishes. Based on evidence from genome‐wide association, coverage, linkage disequilibrium, testis and brain transcriptomes, and sequence conservation with other flatfishes, we propose a mechanism for the recent evolution of an XY sex‐determination mechanism in Atlantic halibut. Changes to the ancestral sex‐determining gene DMRT1 in regulating the downstream gene GSDF probably coincided with GSDF, or a proximal regulatory element of it, becoming the primary sex‐determining factor. Our results suggest changes to a small number of elements can have drastic repercussions for the genomic substrate available to sex‐specific evolutionary forces, providing insight into how certain elements repeatedly evolve to control sex across taxa. Our chromosome‐level assembly, multitissue transcriptomes, and population genomic data provide a valuable resource and understanding of the evolution of sexual systems in fishes.
Pathologic complete response after neoadjuvant tislelizumab and chemotherapy for Pancoast tumor: A case report
Authors: Tang Wen‐Fang , Xu Wei , Huang Wei‐Zhao , Lin Gui‐Nan , Zeng Yu‐Mei , Lin Jie‐Shan , Wu Min , Bao Hua , Peng Jie‐Wen , Jiang Hai‐Ming , Wang Heng‐Qiang , Wu Ying‐Meng , Ye Hong‐Yu , Liang Yi 
Published: March 2021

AbstractA 60‐year‐old man was hospitalized because of numbness and weakness in the right upper limb. Magnetic resonance imaging revealed a large mass in the right upper lobe invading the right eighth cervical and first thoracic nerve root. Biopsy pathology confirmed primary lung adenocarcinoma with a clinical stage of cT4N0M0 IIIA, negative for anaplastic lymphoma kinase fusion gene and epidermal growth factor receptor mutations but positive for programmed death ligand 1 (3%). Neoadjuvant tislelizumab and chemotherapy were offered to this patient with Pancoast tumor, and tumor shrinkage of 71% was achieved. After the operation, surgical pathology indicated pathologic complete response (pCR). Circulating tumor cells testing was negative after the first adjuvant treatment. In this case, we provide real‐world evidence of encouraging pCR with neoadjuvant tislelizumab and chemotherapy for a patient with Pancoast tumor.
Review on Late Pleistocene‐Holocene relative sea‐level changes in Kuwait: New evidence from Failaka island
Authors: Arhan Damien , Pavlopoulos Kosmas , Fouache Éric 
Published: March 2021

AbstractNew results from fieldwork carried out on Failaka island testify to relative sea‐level fluctuations during Late Pleistocene and Holocene. This study is based on analysing, sampling and dating geomorphological sea‐level indicators, including beach ridges or beachrocks. The results have been compared and harmonised with recalibrated data from pre‐existing literature to reconstruct the relative sea‐level local chronology. The vertical displacement identified may have induced coastline mobility and significant environmental changes and impacted the human occupation in Failaka and along the coastal areas of Kuwait. Eventually, the results highlight the impact of large‐scale crustal deformations on regional relative sea‐level variations.
Hydrops fetalis in PKD1L1‐related heterotaxy: Report of two foetuses and expanding the phenotypic and molecular spectrum
Authors: Correa Alec Reginald Errol , Endrakanti Mounika , Naini Kamal , Kabra Madhulika , Gupta Neerja 
Published: March 2021

AbstractAbnormalities in the normal left–right axis asymmetry range from situs inversus totalis to situs ambiguous or heterotaxy. More than 80 genes have been described to have a role in the establishment of the normal situs of the internal organs. Pathogenic variants in the PKD1L1 gene have recently been described in heterotaxy and congenital heart disease. Till date, 11 families have been described with PKD1L1‐related heterotaxy. We describe the first Indian family with two affected foetuses with PKD1L1‐related nonimmune hydrops, congenital heart disease, situs inversus, and heterotaxy, with biallelic variants in the compound heterozygous state.