bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rarefaction-without-resampling extension of PERMANOVA for testing presence-absence associations in the microbiome
Authors: Hu Yi-Juan , Satten Glen A. 
Published: April 2021

AbstractBackgroundPERMANOVA [1] is currently the most commonly used method for testing community-level hypotheses about microbiome associations with covariates of interest. PERMANOVA can test for associations that result from changes in which taxa are present or absent by using the Jaccard or unweighted UniFrac distance. However, such presence-absence analyses face a unique challenge: confounding by library size (total sample read count), which occurs when library size is associated with covariates in the analysis. It is known thatrarefaction(subsampling to a common library size) controls this bias, but at the potential costs of information loss and the introduction of a stochastic component into the analysis.MethodsHere we develop a non-stochastic approach to PERMANOVA presence-absence analyses that aggregates information overallpotential rarefaction replicates without actual resampling, when the Jaccard or unweighted UniFrac distance is used. We compare this new approach to three possible ways of aggregating PERMANOVA over multiple rarefactions obtained from resampling: averaging the distance matrix, averaging the (element-wise) squared distance matrix, and averaging theF-statistic.ResultsOur simulations indicate that our non-stochastic approach is robust to confounding by library size and outperforms each of the stochastic resampling approaches. We also show that, when overdispersion is low, averaging the (element-wise) squared distance outperforms averaging the unsquared distance, currently implemented in the R packagevegan. We illustrate our methods using an analysis of data on inflammatory bowel disease (IBD) in which samples from case participants have systematically smaller library sizes than samples from control participants.
Functional evaluation of the P681H mutation on the proteolytic activation the SARS-CoV-2 variant B.1.1.7 (Alpha) spike
Authors: Lubinski Bailey , Fernandes Maureen H. V. , Frazier Laura , Tang Tiffany , Daniel Susan , Diel Diego G. , Jaimes Javier A. , Whittaker Gary R. 
Published: April 2021

SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing the COVID-19 pandemic. SARS-CoV-2 B.1.1.7 (Alpha), a WHO variant of concern (VOC) first identified in the UK in late 2020, contains several mutations including P681H in the spike S1/S2 cleavage site, which is predicted to increase cleavage by furin, potentially impacting the viral cell entry. Here, we studied the role of the P681H mutation in B.1.1.7 cell entry. We performed assays using fluorogenic peptides mimicking the Wuhan-Hu-1 and B.1.1.7 S1/S2 sequence and observed no significant difference in furin cleavage. Functional assays using pseudoparticles harboring SARS-CoV-2 spikes and cell-to-cell fusion assays demonstrated no differences between Wuhan-Hu-1, B.1.1.7 or a P681H point mutant. Likewise, we observed no differences in viral growth between USA-WA1/2020 and a B.1.1.7 isolate in cell culture. Our findings suggest that while the B.1.1.7 P681H mutation may slightly increase S1/S2 cleavage this does not significantly impact viral entry or cell-cell spread.HighlightsSARS-CoV-2 B.1.1.7 VOC has a P681H mutation in the spike that is predicted to enhance viral infectionP681H does not significantly impact furin cleavage, viral entry or cell-cell spreadOther mutations in the SARS-CoV-2 B.1.1.7 VOC may account for increased infection ratesGraphical abstract
Transcript- and annotation-guided genome assembly of the European starling
Authors: Stuart Katarina C. , Edwards Richard J. , Cheng Yuanyuan , Warren Wesley C. , Burt David W. , Sherwin William B. , Hofmeister Natalie R. , Werner Scott J. , Ball Gregory F. , Bateson Melissa , Brandley Matthew C. , Buchanan Katherine L. , Cassey Phillip , Clayton David F. , De Meyer Tim , Meddle Simone L. , Rollins Lee A. 
Published: April 2021

AbstractThe European starling,Sturnus vulgaris, is an ecologically significant, globally invasive avian species that is also suffering from a major decline in its native range. Here, we present the genome assembly and long-read transcriptome of an Australian-sourced European starling (S. vulgarisvAU), and a second North American genome (S. vulgarisvNA), as complementary reference genomes for population genetic and evolutionary characterisation.S. vulgarisvAU combined 10x Genomics linked-reads, low-coverage Nanopore sequencing, and PacBio Iso-Seq full-length transcript scaffolding to generate a 1050 Mb assembly on 1,628 scaffolds (72.5 Mb scaffold N50). Species-specific transcript mapping and gene annotation revealed high structural and functional completeness (94.6% BUSCO completeness). Further scaffolding against the high-quality zebra finch (Taeniopygia guttata) genome assigned 98.6% of the assembly to 32 putative nuclear chromosome scaffolds. Rapid, recent advances in sequencing technologies and bioinformatics software have highlighted the need for evidence-based assessment of assembly decisions on a case-by-case basis. UsingS. vulgarisvAU, we demonstrate how the multifunctional use of PacBio Iso-Seq transcript data and complementary homology-based annotation of sequential assembly steps (assessed using a new tool, SAAGA) can be used to assess, inform, and validate assembly workflow decisions. We also highlight some counter-intuitive behaviour in traditional BUSCO metrics, and present Buscomp, a complementary tool for assembly comparison designed to be robust to differences in assembly size and base-calling quality. Finally, we present a second starling assembly,S. vulgarisvNA, to facilitate comparative analysis and global genomic research on this ecologically important species.
BDNF Val66Met polymorphism as putative genetic substrate of music-induced plasticity in auditory prediction
Authors: Bruzzone S.E.P. , Bonetti L. , Paunio T. , Kantojärvi K. , Kliuchko M. , Vuust P. , Brattico E. 
Published: April 2021

AbstractPredictive processing of sounds depends on the constant updating of priors based on exposure to posteriors, which through repeated exposure mediates learning. The result of such corrections to the model is seen in musicians, whose lifelong training results in measurable plasticity of audio-motor brain anatomy and functionality. It has been suggested that the plasticity of auditory predictive processes depends on the interaction between the environment and the individual’s genetic substrate. However, empirical evidence to this is still missing. BDNF is a critical genetic factor affecting learning and plasticity, and its widely studied functional variant Val66Met single-nucleotide polymorphism offers a unique opportunity to investigate neuroplastic functional changes occurring upon a years-long training. We hypothesised that BDNF gene variations would be driving neuroplasticity of the auditory cortex in musically trained human participants. To this goal, musicians and non-musicians were recruited and divided in Val/Val and Met carriers and their brain activity measured with magnetoencephalography (MEG) while they listened to a regular auditory sequence containing different types of prediction errors. The auditory cortex responses to prediction errors was enhanced in Val/Val carriers who underwent intensive musical training, compared to Met and non-musicians. Our results point at a role of gene-regulated neurotrophic factors in the neural adaptations of auditory processing after long-term training.
Alkaloid and acetogenin-rich fraction fromAnnona crassiflorafruit peel inhibits proliferation and migration of human liver cancer HepG2 cells
Authors: Justino Allisson B. , Florentino Rodrigo M. , França Andressa , Filho Antonio C. M. L. , Franco Rodrigo R. , Saraiva André L. , Fonseca Matheus C. , Leite Maria F. , Espindola Foued S. 
Published: April 2021

AbstractPlant species from Annonaceae are commonly used in traditional medicine to treat various cancer types. This study aimed to investigate the antiproliferative potential of an alkaloid and acetogenin-rich fraction from the fruit peel ofAnnona crassiflorain HepG2 cells. A liquid-liquid fractionation was carried out on the ethanol extract ofA. crassiflorafruit peel in order to obtain an alkaloid and acetogenin-rich fraction (AF-Ac). Cytotoxicity, proliferation and migration were evaluated in the HepG2 cells, as well as the proliferating cell nuclear antigen (PCNA), vinculin and epidermal growth factor receptor (EGFR) expression. In addition, intracellular Ca2+was determined using Fluo4-AM and fluorescence microscopy. First, 9 aporphine alkaloids and 4 acetogenins that had not yet been identified in the fruit peel ofA. crassiflorawere found in AF-Ac. The treatment with 50 µg/mL AF-Ac reduced HepG2 cell viability, proliferation and migration (p< 0.001), which is in accordance with the reduced expression of PCNA and EGFR levels (p< 0.05). Furthermore, AF-Ac increased intracellular Ca2+in the HepG2 cells, mobilizing intracellular calcium stores, which might be involved in the anti-migration and anti-proliferation capacities of AF-Ac. Our results support the growth-inhibitory potential of AF-Ac on HepG2 cells and suggest that this effect is triggered, at least in part, by PCNA and EGFR modulation and mobilization of intracellular Ca2+. This study showed biological activities not yet described forA. crassiflorafruit peel, which provide new possibilities for furtherin vivostudies to assess the antitumoral potential ofA. crassiflora, especially its fruit peel.
Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp12/7/8 RNA-dependent RNA Polymerase
Authors: Bertolin Agustina P. , Weissmann Florian , Zeng Jingkun , Posse Viktor , Milligan Jennifer C. , Canal Berta , Ulferts Rachel , Wu Mary , Drury Lucy S. , Howell Michael , Beale Rupert , Diffley John F.X. 
Published: April 2021

SummaryThe coronavirus disease 2019 (COVID-19) global pandemic has turned into the largest public health and economic crisis in recent history impacting virtually all sectors of society. There is a need for effective therapeutics to battle the ongoing pandemic. Repurposing existing drugs with known pharmacological safety profiles is a fast and cost-effective approach to identify novel treatments. The COVID-19 etiologic agent is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded positive-sense RNA virus. Coronaviruses rely on the enzymatic activity of the replication-transcription complex (RTC) to multiply inside host cells. The RTC core catalytic component is the RNA-dependent RNA polymerase (RdRp) holoenzyme. The RdRp is one of the key druggable targets for CoVs due to its essential role in viral replication, high degree of sequence and structural conservation and the lack of homologs in human cells. Here, we have expressed, purified and biochemically characterised active SARS-CoV-2 RdRp complexes. We developed a novel fluorescence resonance energy transfer (FRET)-based strand displacement assay for monitoring SARS-CoV-2 RdRp activity suitable for a high-throughput format. As part of a larger research project to identify inhibitors for all the enzymatic activities encoded by SARS-CoV-2, we used this assay to screen a custom chemical library of over 5000 approved and investigational compounds for novel SARS-CoV-2 RdRp inhibitors. We identified 3 novel compounds (GSK-650394, C646 and BH3I-1) and confirmed suramin and suramin-like compounds asin vitroSARS-CoV-2 RdRp activity inhibitors. We also characterised the antiviral efficacy of these drugs in cell-based assays that we developed to monitor SARS-CoV-2 growth.
Tracing patterns of evolution and acquisition of drug resistantAspergillus fumigatusinfection from the environment using population genomics
Authors: Rhodes Johanna , Abdolrasouli Alireza , Dunne Katie , Sewell Thomas R. , Zhang Yuyi , Ballard Eloise , Brackin Amelie P. , van Rhijn Norman , Tsitsopoulou Alexandra , Posso Raquel B. , Chotirmall Sanjay H , McElvaney Noel G , Murphy Philip G , Talento Alida Fe , Renwick Julie , Dyer Paul S. , Szekely Adrien , Bromley Michael J. , Johnson Elizabeth M. , White P. Lewis , Warris Adilia , Barton Richard C. , Schelenz Silke , Rogers Thomas R. , Armstrong-James Darius , Fisher Matthew C. 
Published: April 2021

AbstractInfections caused by opportunistic fungal pathogens are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about the extent to which susceptible patients acquire infection from drug resistant genotypes in the environment. Here, we present a population genomic analysis of the mouldAspergillus fumigatusfrom across the United Kingdom and Republic of Ireland. First, we show occurrences where azole resistant isolates of near identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Second, we find that the fungus is structured into two clades (‘A’ and ‘B’) with little interclade recombination and the majority of environmental azole resistance genetically clustered inside Clade A. Genome-scans show the impact of selective sweeps across multiple regions of the genome. These signatures of positive selection are seen in regions containing canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, whilst other regions under selection have no defined function. Phenotyping identified genes in these regions that could act as modifiers of resistance showing the utility of reverse genetic approaches to dissect the complex genomic architecture of fungal drug resistance. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.
Thunderstruck: The ACDC model of flexible sequences and rhythms in recurrent neural circuits
Authors: Calderon Cristian B. , Verguts Tom , Frank Michael J. 
Published: April 2021

AbstractAdaptive sequential behavior is a hallmark of human cognition. In particular, humans can learn to produce precise spatiotemporal sequences given a certain context. For instance, musicians can not only reproduce learned action sequences in a context-dependent manner, they can also quickly and flexibly reapply them in any desired tempo or rhythm without overwriting previous learning. Existing neural network models fail to account for these properties. We argue that this limitation emerges from the fact that sequence information (i.e., the position of the action) and timing (i.e., the moment of response execution) are typically stored in the same neural network weights. Here, we augment a biologically plausible recurrent neural network of cortical dynamics to include a basal ganglia-thalamic module which uses reinforcement learning to dynamically modulate action. This “associative cluster-dependent chain” (ACDC) model modularly stores sequence and timing information in distinct loci of the network. This feature increases computational power and allows ACDC to display a wide range of temporal properties (e.g., multiple sequences, temporal shifting, rescaling, and compositionality), while still accounting for several behavioral and neurophysiological empirical observations. Finally, we apply this ACDC network to show how it can learn the famous “Thunderstruck” song intro and then flexibly play it in a “bossa nova” rhythm without further training.
Sustainable architecture and earthquake resilience of vernacular Zegalli houses in northern Iran
Authors: Zaryoun Mona , Hosseini Mahmood , Soleymani Kaveh 
Published: April 2021

PurposeThe main purpose of this study is revival of vernacular architecture of Zegalli houses, which can be beneficial in several aspects of sustainable architecture, and therefore, its reuse in contemporary architecture can be strongly recommended. Zegalli houses, in northern Iran, are almost-entirely wooden vernacular houses, which beside to having several aspects of sustainable architecture, have shown good resistance against past earthquakes. Their relatively good seismic performance is mainly because of their specific timber foundation, which creates a kind of rocking/rolling isolation, as well as their light weight and diagonally braced stiff walls.Design/methodology/approachIn this paper, first the architectural features of Zegalli houses, particularly energy efficiency, sustainability and eco-friendliness are described. Then, their structural system, focusing more on their foundation, is discussed. Finally, a simplified model of the house, developed in a powerful finite element analysis program, is introduced, and sample results of a series of time history analyses (THA), employing three-component accelerograms of three selected earthquakes, are presented.FindingsResults of THA show that the rocking/rolling behavior of foundation timbers in various levels significantly reduces seismic response of the house, leading to its stability against earthquakes with peak ground acceleration up to 0.25 g.Practical implicationsRegarding the architectural and structural merits of Zegalli houses, they can be considered as sustainable vernacular architecture, and therefore, architects and civil and structural engineers are encouraged to reconsider the use of these houses, with some modifications, in future developments.Originality/value3D dynamics analysis of Shikilli foundations of Zegalli houses is done for the first time in this study.
Adaptive marketing capability and product innovations: the role of market ambidexterity and transformational leadership (evidence from Pakistani manufacturing industry)
Authors: Ali Shabahat , Wu Weiwei , Ali Sadaqat 
Published: April 2021

PurposeThis study aims to offer and validate an integrated marketing capability-product innovations framework. Particularly, it aims to examine the role of adaptive marketing capability in enabling market ambidexterity and incremental as well as radical product innovation. Also it intends to investigate the moderating role of transformational leadership between adaptive marketing capability and market ambidexterity.Design/methodology/approachManufacturing firms in Pakistan, an emerging economy, are taken as the context for this study. A designed survey questionnaire is used for data collection. Partial least square technique is employed to empirically validate and test the hypothesized model with a sample of 192 manufacturing firms. Particularly, the two-stage approach in SmartPLS is used to validate measurement models, and structural equation modeling technique is used to test the proposed hypothesis.FindingsThe findings not only confirm that adaptive marketing capability is instrumental to both incremental and radical product innovations but also reveal that adaptive marketing capability serves an important antecedent to market ambidexterity shedding new lights on its mediating role in the relationship of adaptive marketing capability with incremental and radical product innovations. Moreover, the results find that the effectiveness of adaptive marketing capability to support market ambidexterity may involve a possible trade-off between exploitation and exploration when the leaders exhibit a low or high level of transformational leadership behavior.Originality/valueThis study contributes to outside-in strategic perspective and contextual ambidexterity literature by revealing the role of adaptive marketing capability as an important enabler of market ambidexterity which, in turn, allows the firm to simultaneously introduce incremental and radical product innovations. In this way, this study advances the current understanding of the antecedents and consequences of contextual ambidexterity. Also, this study provides insight into the types of capabilities needed for the firm's contextual and employees' behavioral adaptation to simultaneously manage exploitation and exploration within the same business unit which was lacking in the previous literature. Further, this study also offers a novel understanding of the conditional role of transformational leadership between adaptive marketing capability and market ambidexterity.
Reciprocity or negotiation in the psychological contract: a power perspective
Authors: Ali Haris 
Published: April 2021

PurposeThe psychological contract literature is generally based on the assumption of reciprocity between employee and employer. The emphasis on reciprocity, however, largely downplays the implications of power dynamics in the employment relationship. In order to bridge this gap, the current research investigates psychological contract from the lens of power particularly focusing on reciprocity.Design/methodology/approachIn total, 43 semi-structured interviews are carried out with 37 employees and six managers of three call center companies in Pakistan. The technique of template analysis is used for data analysis.FindingsIn contrast to the assumption of reciprocity, the research findings highlight employees' perceived inability to reciprocate the employer's inducements on parity basis, because of their view of power asymmetry in the employment relationship. The results further suggest the high tendency among employees to attribute employer reciprocity largely to their managers. The findings also point toward divergence in the reciprocity perceptions of employees and managers in relation with the employers.Research limitations/implicationsThe emphasis on call centers bounds the generality of results. Future research is needed to further explore the impact of power asymmetry on reciprocity in organizations of other industries. With significant implications for the employment relations, negotiated contracts consider the exchange between employee and employer as an obligation rather than a voluntary act of kindness, as emphasized in reciprocity.Originality/valueThis research contributes to knowledge by emphasizing the significance of negotiation rather than reciprocation in the psychological contract. The negotiation approach efficiently recognizes the implications of power asymmetry that remain generally under-researched in the psychological contract literature.
Affordable housing policies in a post-COVID aftermath
Authors: Andres Fernandez Mario , Martin Shane L. 
Published: April 2021

Purpose
The purpose of this paper is to assess the outcomes of a suite of affordability policies in Auckland, New Zealand, in the face of a post-COVID aftermath. Improving the access to homeownership while preserving the competitive nature of the housing market will remain a critical goal for New Zealand.

Design/methodology/approach
This paper develops a spatially delineated one-to-one matching model to assess affordable housing policies such as the targeting of houses to target population groups, a shared ownership/equity scheme and the cascading (or release) of the developed affordable houses into the broader market.

Findings
Results show that a targeting programme with an income threshold set between $120,000 and $150,000 maximises house sales, but a threshold set at $96,000 maximises the number of moderate-income households becoming homeowners. Several parameterisations of the model demonstrate the potential contradictions (or overlaps) between policy goals.

Originality/value
The contribution of this paper is a deeper understanding of the market outcomes of affordability policies, and inputs to design strategies that balance market efficiency and fairness. Also, this paper shows that stronger integration across governments (central and local) and actors of the housing market.