bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of COVID-19 vaccination campaigns accounting for antibody-dependent enhancement
Authors: Adil Nessma M. Y. , Obama H. Christian Tsoungui , Ngucho Jordan Y. , Kwamou S. Frank , Kayanula Loyce , Kamanga George , Ibrahim Toheeb B. , Iliya Patience Bwanu , Iyanda Sulyman , Alawam Looli , Helle Kristina B. , Teboh-Ewungkem Miranda I. , Schneider Kristan A. 
Published: January 2021

AbstractBackgroundCOVID-19 vaccines are approved, vaccination campaigns are launched, and worldwide return to normality seems within close reach. Nevertheless, concerns about the safety of COVID-19 vaccines arose, due to their fast emergency approval. In fact, the problem of antibody-dependent enhancement was raised in the context of COVID-19 vaccines.Methods and findingsWe introduce a complex extension of the model underlying the pandemic preparedness tool CovidSim 1.1 (http://covidsim.eu/) to optimize vaccination strategies with regard to the onset of campaigns, vaccination coverage, vaccination schedules, vaccination rates, and efficiency of vaccines. Vaccines are not assumed to immunize perfectly. Some individuals fail to immunize, some reach only partial immunity, and – importantly – some develop antibody-dependent enhancement, which increases the likelihood of developing symptomatic and severe episodes (associated with higher case fatality) upon infection. Only a fraction of the population will be vaccinated, reflecting vaccination hesitancy or contraindications. The model is intended to facilitate decision making by exploring ranges of parameters rather than to be fitted by empirical data.We parameterized the model to reflect the situation in Germany and predict increasing incidence (and prevalence) in early 2021 followed by a decline by summer. Assuming contact reductions (curfews, social distancing, etc.) to be lifted in summer, disease incidence will peak again. Fast vaccine deployment contributes to reduce disease incidence in the first quarter of 2021, and delay the epidemic outbreak after the summer season. Higher vaccination coverage results in a delayed and reduced epidemic peak. A coverage of 75% - 80% is necessary to prevent an epidemic peak without further drastic contact reductions.ConclusionsWith the vaccine becoming available, compliance with contact reductions is likely to fade. To prevent further economic damage from COVID-19, high levels of immunization need to be reached before next year’s flu season, and vaccination strategies and disease management need to be flexibly adjusted. The predictive model can serve as a refined decision support tool for COVID-19 management.
A workflow for simultaneous detection of coding and non-coding transcripts by ribosomal RNA-depleted RNA-Seq
Authors: Potemkin Nikita , Cawood Sophie M.F. , Treece Jackson , Guévremont Diane , Rand Christy J. , McLean Catriona , Stanton Jo-Ann L. , Williams Joanna M. 
Published: January 2021

AbstractRNA sequencing offers unprecedented access to the transcriptome. Key to this is the identification and quantification of many different species of RNA from the same sample at the same time. In this study we describe a novel protocol for simultaneous detection of coding and non-coding transcripts using modifications to the Ion Total RNA-Seq kit v2 protocol, with integration of QIASeq FastSelect rRNA removal kit. We report highly consistent sequencing libraries can be produced from both frozen high integrity mouse hippocampal tissue and the more challenging post-mortem human tissue. Removal of rRNA using FastSelect was highly efficient, resulting in less than 1.5% rRNA content in the final library, significantly better than other reported rRNA removal techniques. We identified >30,000 unique transcripts from all samples, including protein-coding genes and many unique species of non-coding RNA, in biologically-relevant proportions. Furthermore, normalized sequencing read count for select genes significantly negatively correlated with Ct values from RT-qPCR analysis from the same samples. These results indicate that this protocol accurately and consistently identifies and quantifies a wide variety of transcripts simultaneously. The highly efficient rRNA depletion, coupled with minimized sample handling and without complicated and high-loss size selection protocols, makes this protocol useful to researchers wishing to investigate whole transcriptomes.
Metronomic therapy prevents emergence of drug resistance by maintaining the dynamic of intratumor heterogeneity
Authors: Bondarenko Maryna , Grand Marion Le , Shaked Yuval , Raviv Ziv , Chapuisat Guillemette , Carrère Cécile , Montero Marie-Pierre , Rossi Mailys , Pasquier Eddy , Carré Manon , André Nicolas 
Published: January 2021

AbstractDespite recent advances in deciphering cancer drug resistance mechanisms, relapse is a widely observed phenomenon in advanced cancers, mainly due to intratumor clonal heterogeneity. How tumor clones progress and impact each other remains elusive. By better understanding clone dynamics, we could reveal valuable biological insights and unveil vulnerabilities that could be therapeutically exploited. In this study, we developed 2D and 3D non-small cell lung cancer co-culture systems and defined a phenomenological mathematical model. Our results demonstrated a dominant role of the drug-sensitive clones over the drug-resistant ones under untreated conditions. Model predictions and their experimentalin vitroandin vivovalidations indicated that metronomic schedule leads to a better regulation of tumor cell heterogeneity over time than maximum-tolerated dose schedule, while achieving control of global tumor progression. We finally showed that drug-sensitive clones exert a suppressive effect on the proliferation of the drug-resistant ones through a paracrine mechanism way, which is linked to metabolic cell clone activity. Altogether, these computational and experimental approaches allow assessment of drug schedules controlling drug-sensitive and -resistant clone balance and highlight the potential of targeting cell metabolism to manage intratumor heterogeneity.SignificanceCombined computational and experimental models reveal how drug-sensitive tumor cells exert their dominance over drug-resistant cells and how it impacts optimal chemotherapy scheduling.
Genetic analysis of DinG-family helicase YoaA and its interaction with replication clamp-loader protein HolC inE. coli
Authors: Sutera Vincent A. , Sass Thalia H. , Leonard Scott E. , Wu Lingling , Glass David J. , Giordano Gabriela G. , Zur Yonatan , Lovett Susan T. 
Published: January 2021

ABSTRACTThe XP-D/DinG family of DNA helicases contribute to genomic stability in all three domains of life. We investigate here the role of one of these proteins,YoaA, ofEscherichia coli. InE. coli,YoaA aids tolerance to the nucleoside azidothymidine (AZT), a DNA replication inhibitor and physically interacts with a subunit of the DNA polymerase III holoenzyme, HolC. We map the residues of YoaA required for HolC interaction to its C-terminus by yeast two-hybrid analysis. We propose that this interaction competes with HolC’s interaction with HolD and the rest of the replisome;YoaA indeed inhibits growth when overexpressed, dependent on this interaction region. By gene fusions we show YoaA is repressed by LexA and induced in response to DNA damage as part of the SOS response. Induction of YoaA by AZT is biphasic with an immediate response after treatment and a slower response that peaks in the late log phase of growth. This growth-phase dependent induction by AZT is not blocked bylexA3(Ind-), which normally negates its self-cleavage, implying another means to induce the DNA damage response that responds to the nutritional state of the cell. We propose that YoaA helicase activity increases access to the 3’ nascent strand during replication; consistent with this,YoaA appears to aid removal of potential A-to-T transversion mutations inndkmutants, which are prone to nucleotide misincorporation. YoaA and its paralog DinG also may initiate template-switching that leads to deletions between tandem repeats in DNA.IMPORTANCEMaintaining genomic stability is crucial for all living organisms. Replication of DNA frequently encounters barriers that must be removed to complete genome duplication. Balancing DNA synthesis with its repair is critical and not entirely understood at a mechanistic level.The YoaA protein, studied here, is required for certain types of DNA repair and interacts in an alternative manner with proteins that catalyze DNA replication. YoaA is part of the well-studied LexA-regulated response to DNA damage, the SOS response. We describe an unusual feature of its regulation that promotes induction after DNA damage as the culture begins to experience starvation. Replication fork repair integrates both DNA damage and nutritional signals. We also show that YoaA affects genomic stability.
Quantification of biologically and chemically bound phosphorus in activated sludge from full-scale plants with biological P-removal
Authors: Petriglieri Francesca , Petersen Jette F. , Peces Miriam , Nierychlo Marta , Hansen Kamilla , Baastrand Cecilie E. , Nielsen Ulla Gro , Reitzel Kasper , Nielsen Per Halkjær 
Published: January 2021

AbstractLarge amounts of phosphorus (P) are present in activated sludge from municipal wastewater treatment plants, where it exists in the form of metal salt precipitates or biologically bound into the biomass as nucleic acids, cell membrane components, and the extracellular polymeric substances or, in special polyphosphate-accumulating organisms (PAOs), as intracellular polyphosphate. Only recently, methods that reliably allow an absolute quantification of the different P-fractions, such as sequential extraction, Raman microspectroscopy, solid-state31P magic angle spinning (MAS) NMR, and solution state31P NMR have been developed. This study combines these techniques to obtain a comprehensive P mass-balance of activated sludge from four wastewater treatment plants with enhanced biological phosphate removal (EBPR). The total content of P and various cations was measured by chemical analysis (ICP-OES), and different P fractions were extracted for chemical characterization. Chemically bound P constituted 38-69% of total P, most likely in the form of Fe, Mg, or Al minerals, while organically bound P constituted 7-9%. By using Raman microspectroscopy and solution state31P NMR and31P MAS NMR spectroscopy before and after anaerobic P-release experiments, poly-P was quantified and constituted 22-54% of total P in the activated sludges and was found in approx. 25% of all bacterial cells. Moreover, Raman microspectroscopy in combination with fluorescencein situhybridization (FISH) was used to quantify the species-specific intracellular poly-P of known PAO genera (Tetrasphaera,Ca.Accumulibacter,Dechloromonas) and other microorganisms known to possess high level of poly-P, such as the filamentousCa.Microthrix. They were all abundant, as measured by quantitative-FISH and amplicon sequencing, and accumulated large amount of poly-P, depending on their cell-size, contributing substantially to the P-removal. Interestingly, in all four EBPR plants investigated, only 1-13% of total poly-P was stored by unidentified PAO, highlighting that most PAOs in the full-scale EBPR plants investigated are now known.HighlightsExhaustive P mass-balance of main organic and inorganic P-species in four EBPR plantsQuantification of poly-P of FISH-defined PAO and other species with high P contentTotal P content was 36-50 mgP/gSS of which 31-62% was in biomass and as poly-PA high fraction of all cells (25-30%) contained a high content of poly-PKnown PAOs contained almost all poly-P in the EBPR plants investigated
Functionality of the putative surface glycoproteins of the Wuhan spiny eel influenza virus
Authors: Arunkumar Guha Asthagiri , Strohmeier Shirin , Li Tiehai , Bhavsar Disha , Chromikova Veronika , Amanat Fatima , Bunyatov Mehman , Wilson Patrick C. , Ellebedy Ali H. , Boons Geert-Jan , Simon Viviana , de Vries Robert P. , Krammer Florian 
Published: January 2021

AbstractA panel of novel influenza-like virus sequences were recently documented in jawless fish, ray-finned fish, and amphibians. Of these, the Wuhan spiny eel influenza virus (WSEIV) was found to phylogenetically cluster with influenza B viruses as a sister clade. Influenza B viruses have been historically documented to circulate only in humans, with certain virus isolates found in harbor seals. It is therefore interesting that a similar virus was potentially found in fish. Here we characterized the functionality and antigenicity of the putative hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins of the WSEIV to better understand this virus and its pandemic potential. Upon functional characterization of NA, we identified that the WSEIV NA-like protein has sialidase activity comparable to B/Malaysia/2506/2004 influenza B virus NA, making it abona fideneuraminidase that could be inhibited by NA inhibitors. Testing of the functionality of HA was carried out including receptor specificity, stability, and preferential airway protease cleavage and showed very specific binding to monosialic ganglioside 2 (GM2). To probe the degree of conservation of target epitopes, binding of known broadly cross-reactive monoclonal antibodies targeting the influenza B HA and NA, respectively, were assessed through enzyme linked immunosorbent assays against recombinant WSEIV glycoproteins. Human serum samples of patients with antibodies to influenza B viruses were used to determine the cross-reactivity against these novel glycoproteins. Very few monoclonal antibodies – notably including pan NA antibody 1G01 - showed cross-reactivity and reactivity from human sera was basically absent. In summary, we have conducted a functional and antigenic characterization of the glycoproteins of the novel WSEIV to assess if it is indeed abona fideinfluenza virus potentially circulating in ray-finned fish.
Multiple concurrent feedforward and feedback streams in a cortical hierarchy
Authors: Barzegaran Elham , Plomp Gijs 
Published: January 2021

AbstractVisual stimuli evoke fast-evolving activity patterns that are distributed across multiple cortical areas. These areas are hierarchically structured, as indicated by their anatomical projections, but how large-scale feedforward and feedback streams are functionally organized in this system remains an important missing clue to understanding cortical processing. By analyzing visual evoked responses in laminar recordings from six cortical areas in awake mice, we established the simultaneous presence of two feedforward and two feedback networks, each with a distinct laminar functional connectivity profile, frequency spectrum, temporal dynamics and functional hierarchy. We furthermore identified a distinct role for each of these four processing streams, by leveraging stimulus contrast effects and analyzing receptive field convergency along functional interactions. Our results support a dynamic dual counterstream view of hierarchical processing and provide new insight into how separate functional streams can simultaneously and dynamically operate in visual cortex.
TMPRSS2 structure-phylogeny repositions Avoralstat for SARS-CoV-2 prophylaxis in mice
Authors: Joo Sun Young , Velez Gabriel , Parsons Dylan , Li Kun , Ortiz Miguel , Sharma Shaunik , McCray Paul B. , Bassuk Alexander G. , Mahajan Vinit B. 
Published: January 2021

SummaryDrugs targeting host proteins can act prophylactically to reduce viral burden early in disease and limit morbidity, even with antivirals and vaccination. Transmembrane serine protease 2 (TMPRSS2) is a human protease required for SARS-CoV-2 viral entry and may represent such a target.1–3We hypothesized drugs selected from proteins related by their tertiary structure, rather than their primary structure, were likely to interact with TMPRSS2. We created a structure-based phylogenetic computational tool 3DPhyloFold to systematically identify structurally similar serine proteases with known therapeutic inhibitors and demonstrated effective inhibition of SARS-CoV-2 infectionin vitroandin vivo.4,5Several candidate compounds, Avoralstat, PCI-27483, Antipain, and Soybean-Trypsin-Inhibitor, inhibited TMPRSS2 in biochemical and cell infection assays. Avoralstat, a clinically tested Kallikrein-related B1 inhibitor,6inhibited SARS-CoV-2 entry and replication in human airway epithelial cells. In anin vivoproof of principle,5Avoralstat significantly reduced lung tissue titers and mitigated weight-loss when administered prophylactically to SARS-CoV-2 susceptible mice indicating its potential to be repositioned for COVID-19 prophylaxis in humans.
KERA: Analysis Tool for Multi-Process, Multi-State Single-Molecule Data
Authors: Tibbs Joseph , Ghoneim Mohamed , Caldwell Colleen C. , Buzynski Troy , Bowie Wayne , Boehm Elizabeth M. , Washington M. Todd , Tabei S. M. Ali , Spies Maria 
Published: January 2021

ABSTRACTMolecular machines within cells dynamically assemble, disassemble, and reorganize. Molecular interactions between their components can be observed at the single-molecule level and quantified using colocalization single-molecule spectroscopy (CoSMoS), in which individual labeled molecules are seen transiently associating with a surface-tethered partner, or other total internal reflection fluorescence microscopy (TIRFM) approaches in which the interactions elicit changes in fluorescence in the labeled surface-tethered partner. When multiple interacting partners can form ternary, quaternary and higher order complexes, the types of spatial and temporal organization of these complexes can be deduced from the order of appearance and reorganization of the components. Time evolution of complex architectures can be followed by changes in the fluorescence behavior in multiple channels. Here, we describe the kinetic event resolving algorithm (KERA), a software tool for organizing and sorting the discretized fluorescent trajectories from a range of single-molecule experiments. KERA organizes the data in groups by transition patterns, and displays exhaustive dwell-time data for each interaction sequence. Enumerating and quantifying sequences of molecular interactions provides important information regarding the underlying mechanism of the assembly, dynamics and architecture of the macromolecular complexes. We demonstrate KERA’s utility by analyzing conformational dynamics of two DNA binding proteins: RPA and XPD helicase.
Does green intellectual capital spur corporate environmental performance through green workforce?
Authors: Mansoor Adil , Jahan Sarwat , Riaz Madiha 
Published: January 2021

PurposeDrawing upon the intellectual capital-based view theory, this study explored the relationship between green intellectual capital (IC) and environmental performance (EP) with the intervening effect of green human resource management (GHRM).Design/methodology/approachCross-sectional data were collected from 187 human resource directors/managers working in manufacturing firms of Pakistan. A partial least squares approach was applied to test the hypothesized relationships.FindingsThe results showed a mediating effect of GHRM on the relationship between green human capital and the organizational EP. Also two dimensions of green IC (green human capital, green relational capital) were also found positively related to the EP of the firm.Practical implicationsPolicymakers should devote their attention to the preservation and enhancement of their employees' knowledge as green human capital is possessed by the employees. Furthermore, managers must exchange information with key stakeholders to better understand and resolve their environmental concerns. Organizational leaders must also ensure the implementation of GHRM policies that, in turn, improve the EP with the aid of green IC.Originality/valueThe current research contributes to the literature by defining green IC as an antecedent and GHRM as an intervening variable for EP. In addition, this study underlines the significance of GHC as a valuable intangible asset for the achievement of environmental sustainability. It also illustrates the importance of GRC, which creates an exchange partnership with the stakeholders to promote corporate environmentalism.
Ease of market entry of Indian startups: formal and informal institutional influences
Authors: Scillitoe Joanne L. , Birasnav Muthuraj 
Published: January 2021

PurposeThe purpose of this study offers a theoretical model, hypotheses and empirical analyses of how formal and informal institutions influence the ease of market entry of startups in the context of India.Design/methodology/approachA theoretical model based upon institutional and market entry theories is presented with hypotheses. Structural equation modeling is used to test the hypotheses.FindingsResults of the study suggest that college preparations and a culture of creativity and innovation are positively related to ease of market entry by Indian startups. A culture of personal success is negatively related to ease of market entry. Government assistance related to ease of market entry is not significant.Originality/valueThis paper offers a new perspective, linking formal and informal institutional influences to startup ease of market entry. In addition, informal institutions are viewed from the cultures of personal success and creativity/innovation within the entrepreneurial domain, which is also new to the literature. This paper offers specific insights in the context of India startups and offers some interesting findings that can contribution to the literature, policy and practice.
Relationship heterogeneity in Taiwanese maritime logistics service supply chains
Authors: Lin Moses Shang-Min , Potter Andrew , Pettit Stephen 
Published: January 2021

Purpose
With the diverse, heterogeneous nature of relationships being a key characteristic of service supply chains, their management is an important area for consideration. This is particularly true in the maritime logistics industry, yet the factors that lead to this heterogeneity are less well understood. This paper aims to explore the structure of relationships within the maritime logistics network and determine why they vary.

Design/methodology/approach
Interviews were carried out with 41 practitioners involved in the Taiwanese maritime logistics network. The data from these interviews were analyzed using thematic analysis and quasi-quantification.

Findings
The interviews identify that structural holes exist within this maritime logistics network, and that these particularly influence the relationships within this sector with ports being significantly affected. However, five factors are particularly identified that can further impact the strength of these relationships. Often, weak links between ports and both cargo owners and freight forwarders emerge as value-added services are provided by the network.

Research limitations/implications
The findings are framed in a Taiwanese context, where cultural and political norms may give different results to other geographical regions. The research also limits consideration to containerized flows.

Practical implications
By providing detailed insights into relationship structures within the maritime logistics network, managers can take steps to develop appropriate links with other members of the network, reflecting upon the factors that lead to heterogeneity.

Originality/value
This paper expands knowledge on logistics service supply chains, identifying the importance of relationships in a derived demand environment. For maritime researchers, specific factors leading to relationship heterogeneity in the network are detailed, to inform future research.