bluuebunny/crossref_metadata_2025_split huggingface dataset:
A western representative of an eastern clade: phylogeographic history of the gypsophilous plant Nepeta hispanica
Authors: Ramos-Gutiérrez Ignacio , Moreno-Saiz Juan Carlos , Fernández-Mazuecos Mario 
Published: January 2022

AbstractThe preference of certain plant species for gypsum soils leads to disjunct population structures that are thought to generate island-like dynamics potentially influencing biogeographic patterns at multiple evolutionary scales. Here, we study the evolutionary and biogeographic history of Nepeta hispanica, a western Mediterranean plant associated with gypsum soils and displaying a patchy distribution with populations very distant from each other. Three approaches were used: (a) interspecific phylogenetic analyses based on nuclear DNA sequences of the ITS region to unveil the relationships and times of divergence between N. hispanica and its closest relatives; ((b)phylogeographic analyses using plastid DNA regions trnS-trnG and psbJ-petA to evaluate the degree of genetic isolation between populations of N. hispanica, their relationships and their genetic diversity; and (c) ecological niche modelling to evaluate historical distributional changes. Results reveal that N. hispanica belongs to an eastern Mediterranean and Asian clade diversified in arid environments since the Miocene-Pliocene. This species represents the only extant lineage of this clade that colonized the western Mediterranean, probably through the northern Mediterranean coast (southern Europe). Present Iberian populations display a high plastid genetic diversity and, even if geographically distant from each other, they are highly connected according to the distribution of plastid haplotypes and lineages. This can be explained by a scenario involving a complex history of back-and-forth colonisation events, facilitated by a relative stability of suitable conditions for the species across the Iberian Peninsula throughout the Quaternary.
The role of collegiality in academic review, promotion, and tenure
Authors: Dawson Diane , Morales Esteban , McKiernan Erin C. , Schimanski Lesley A. , Niles Meredith T. , Alperin Juan Pablo 
Published: January 2022

AbstractReview, promotion, and tenure (RPT) processes at universities typically assess candidates along three dimensions: research, teaching, and service. In recent years, some have argued for the inclusion of a controversial fourth criterion: collegiality. While collegiality plays a role in the morale and effectiveness of academic departments, it is amorphic and difficult to assess, and could be misused to stifle dissent or enforce homogeneity. Despite this, some institutions have opted to include this additional element in their RPT documents and processes, but it is unknown the extent of this practice and how it varies across institution type and disciplinary units. This study is based on two sets of data: survey data collected as part of a project that explored the publishing decisions of faculty and how these related to perceived importance in RPT processes, and 864 RPT documents collected from 129 universities from the United States and Canada. We analysed these RPT documents to determine the degree to which collegiality and related terms are mentioned, if they are defined, and if and how they may be assessed during the RPT process. Results show that when collegiality and related terms appear in these documents they are most often just briefly mentioned. It is less common for collegiality and related terms to be defined or assessed in RPT documents. Although the terms are mentioned across all types of institutions, there is a statistically significant difference in how prevalent they are at each. Collegiality is more commonly mentioned in the documents of doctoral research-focused universities (60%), than of master’s universities and colleges (31%) or baccalaureate colleges (15%). Results from the accompanying survey of faculty also support this finding: individuals from R-Types were more likely to perceive collegiality to be a factor in their RPT processes. We conclude that collegiality likely plays an important role in RPT processes, whether it is explicitly acknowledged in policies and guidelines or not, and point to several strategies in how it might be best incorporated in the assessment of academic careers.
Integrin signaling is critical for myeloid-mediated support of T-cell acute lymphoblastic leukemia
Authors: Lyu Aram , Nam Seo Hee , Humphrey Ryan S. , Durham Tyler A. , Hu Zicheng , Arasappan Dhivya , Horton Terzah M. , Ehrlich Lauren I. R. 
Published: January 2022

AbstractWe previously found that T-cell acute lymphoblastic leukemia (T-ALL) requires support from tumor-associated myeloid cells, which activate IGF1R signaling in the leukemic blasts. However, IGF1 is not sufficient to sustain T-ALL survival in vitro, implicating additional myeloid-mediated signals in T-ALL progression. Here, we find that T-ALL cells require close contact with myeloid cells to survive. Transcriptional profiling and in vitro assays demonstrate that integrin-mediated cell adhesion and activation of the downstream FAK/PYK2 kinases are required for myeloid-mediated support of T-ALL cells and promote IGF1R activation. Consistent with these findings, inhibition of integrins or FAK/PYK2 signaling diminishes leukemia burden in multiple organs and confers a survival advantage in a mouse model of T-ALL. Inhibiting integrin-mediated cell adhesion or FAK/PYK2 also diminishes survival of primary patient T-ALL cells co-cultured with myeloid cells. Furthermore, elevated integrin pathway gene signatures correlate significantly with myeloid enrichment and an inferior prognosis in pediatric T-ALL patients.Statement of significanceAlthough tumor-associated myeloid cells provide critical support for T-ALL, our understanding of the underlying mechanisms remains limited. This study reveals that integrin-mediated adhesion and signaling are key mechanisms by which myeloid cells promote survival and progression of T-ALL blasts in the leukemic microenvironment.
Molecular Mechanism of Hyperactivation Conferred by a Truncated TRPA1 Disease Mutant Suggests New Gating Insights
Authors: Bali Avnika , Schaefer Samantha P. , Trier Isabelle , Zhang Alice L. , Kabeche Lilian , Paulsen Candice E. 
Published: January 2022

ABSTRACTThe wasabi receptor, TRPA1, is a non-selective homotetrameric cation channel expressed in primary sensory neurons of the pain pathway, where it is activated by diverse chemical irritants. A direct role for TRPA1 in human health has been highlighted by the discovery of genetic variants associated with severe pain disorders. One such TRPA1 mutant was identified in a father-son pair with cramp fasciculation syndrome (CFS) and neuronal hyperexcitability-hypersensitivity symptoms that may be caused by aberrant channel activity, though the mechanism of action for this mutant is unknown. Here, we show the CFS-associated R919* TRPA1 mutant is functionally inactive when expressed alone in heterologous cells, which is not surprising since it lacks the 201 C-terminal amino acids that house critical channel gating machinery including the pore-lining transmembrane helix. Interestingly, the R919* mutant confers enhanced agonist sensitivity when co-expressed with wild type (WT) TRPA1. This channel hyperactivation mechanism is conserved in distant TRPA1 species orthologues and can be recapitulated in the capsaicin receptor, TRPV1. Using a combination of ratiometric calcium imaging, immunostaining, surface biotinylation, pulldown assays, fluorescence size exclusion chromatography, and proximity biotinylation assays, we show that the R919* mutant co-assembles with WT subunits into heteromeric channels. Within these heteromers, we postulate that R919* TRPA1 subunits contribute to hyperactivation by lowering energetic barriers to channel activation contributed by the missing regions. Additionally, we show heteromer activation can originate from the R919* TRPA1 subunits, which suggests an unexpected role for the ankyrin repeat and coiled coil domains in concerted channel gating. Our results demonstrate the R919* TRPA1 mutant confers gain-of-function thereby expanding the physiological impact of nonsense mutations, reveals a novel and genetically tractable mechanism for selective channel sensitization that may be broadly applicable to other receptors, and uncovers new gating insights that may explain the molecular mechanism of temperature sensing by some TRPA1 orthologues.
Machine learning guided batched design of a bacterial Ribosome Binding Site
Authors: Zhang Mengyan , Holowko Maciej Bartosz , Zumpe Huw Hayman , Ong Cheng Soon 
Published: January 2022

AbstractOptimisation of gene expression levels is an essential part of the organism design process. Fine control of this process can be achieved through engineering transcription and translation control elements, including the ribosome binding site (RBS). Unfortunately, design of specific genetic parts can still be challenging due to lack of reliable design methods. To address this problem, we have created a machine learning guided Design-Build-Test-Learn (DBTL) cycle for the experimental design of bacterial RBSs to show how small genetic parts can be reliably designed using relatively small, high-quality data sets. We used Gaussian Process Regression for the Learn phase of cycle and the Upper Confidence Bound multi-armed bandit algorithm for the Design of genetic variants to be tested in vivo. We have integrated these machine learning algorithms with laboratory automation and high-throughput processes for reliable data generation. Notably, by Testing a total of 450 RBS variants in four DBTL cycles, we experimentally validated RBSs with high translation initiation rates equalling or exceeding our benchmark RBS by up to 34%. Overall, our results show that machine learning is a powerful tool for designing RBSs, and they pave the way towards more complicated genetic devices.
CRISPR-LRS for mapping transgenes in the mouse genome
Authors: Bryant W. Bart , Yang Allison , Griffin Susan , Zhang Wei , Long Xiaochun , Miano Joseph M. 
Published: January 2022

AbstractMicroinjected transgenes, including bacterial artificial chromosomes (BACs), insert randomly in the mouse genome. Traditional methods of mapping a transgene are challenging, thus complicating breeding strategies and the accurate interpretation of phenotypes, particularly when a transgene disrupts critical coding or noncoding sequences. Here, we introduce CRISPR-Cas9 long-read sequencing (CRISPR-LRS) to ascertain transgene integration locus and estimated copy number. This method revealed integration loci for both a BAC and Cre-driver line, and estimated the copy numbers for two other BAC mouse lines. CRISPR-LRS offers an easy approach to establish robust breeding practices and accurate phenotyping of most any transgenic mouse line.
Unravelling microalgal-bacterial interactions in aquatic ecosystems through 16S rRNA gene-based co-occurrence networks
Authors: Pushpakumara B.L.D. Uthpala , Tandon Kshitij , Willis Anusuya , Verbruggen Heroen 
Published: January 2022

AbstractInteractions between microalgae and bacteria can directly influence the global biogeochemical cycles but the majority of such interactions remain unknown. 16S rRNA gene-based co-occurrence networks have potential to help identify microalgal-bacterial interactions. Here, we used data from 10 Earth microbiome projects to identify potential microalgal-bacterial associations in aquatic ecosystems. A high degree of clustering was observed in microalgal-bacterial modules, indicating densely connected neighbourhoods.ProteobacteriaandBacteroidetespredominantly co-occurred with microalgae and represented hubs of most modules. Our results also indicated that species-specificity may be a global characteristic of microalgal associated microbiomes. Several previously known associations were recovered from our network modules, validating that biologically meaningful results can be inferred using this approach. A range of previously unknown associations were recognised such as co-occurrences ofBacillariophytawith unculturedPlanctomycetes OM190andDeltaproteobacteriaorderNB1-j. PlanctomycetesandVerrucomicrobiawere identified as key associates of microalgae due to their frequent co-occurrences with several microalgal taxa. Despite no clear taxonomic pattern, bacterial associates appeared functionally similar across different environments. To summarise, we demonstrated the potential of 16S rRNA gene-based co-occurrence networks as a hypothesis-generating framework to guide more focused research on microalgal-bacterial associations.
Function and constraint in enhancers with multiple evolutionary origins
Authors: Fong Sarah L. , Capra John A. 
Published: January 2022

AbstractMotivationThousands of human gene regulatory enhancers are composed of sequences with multiple evolutionary origins. These evolutionarily “complex” enhancers consist of older “core” sequences and younger “derived” sequences. However, the functional relationship between the sequences of different evolutionary origins within complex enhancers is poorly understood.ResultsWe evaluated the function, selective pressures, and sequence variation across core and derived components of human complex enhancers. We find that both components are older than expected from the genomic background, and cores are enriched for derived sequences of similar evolutionary ages. Both components show strong evidence of biochemical activity in massively parallel report assays (MPRAs). However, core and derived sequences have distinct transcription factor (TF) binding preferences that are largely stable across evolutionary origins. Given these signatures of function, both core and derived sequences have substantial evidence of purifying selection. Nonetheless, derived sequences exhibit weaker purifying selection than adjacent cores. Derived sequences also tolerate more common genetic variation and are enriched compared to cores for eQTL associated with gene expression variability in human populations.ConclusionsBoth core and derived sequences have strong evidence of gene regulatory function, but derived sequences have distinct constraint profiles, TF binding preferences, and tolerance to variation compared with cores. We propose that the step-wise integration of younger derived and older core sequences has generated regulatory substrates with robust activity and the potential for functional variation. Our analyses demonstrate that synthesizing study of enhancer evolution and function can aid interpretation of regulatory sequence activity and functional variation across human populations.Significance StatementThousands of human gene regulatory enhancers are mosaics of sequences from multiple evolutionary origins, yet how these different segments contribute to enhancer function is poorly understood. By dissecting their regulatory functions, transcription factor binding, constraint, and human genetic variation, we show that both older “core” and younger “derived” sequences in complex enhancers have strong evidence of gene regulatory function, but derived sequences are more likely to harbor genetic variants that influence function. Together, our results support a model in which the integration of sequences of different origins generates regulatory substrates with robust activity and the potential for functional variation.
An integrated lab-on-a-chip device for RNA extraction, amplification and CRISPR-Cas12a-assisted detection for COVID-19 screening in resource-limited settings
Authors: Ngamsom Bongkot , Iles Alexander , Kamita Moses , Kimani Racheal , Rodriguez-Mateos Pablo , Mungai Mary , Dyer Charlotte E. , Walter Cheryl , Gitaka Jesse , Pamme Nicole 
Published: January 2022

AbstractIn response to the ongoing COVID-19 pandemic and disparities of vaccination coverage in low- and middle-income countries, it is vital to adopt a widespread testing and screening programme, combined with contact tracing, to monitor and effectively control the infection dispersion in areas where medical resources are limited. This work presents a lab-on-a-chip platform, namely “IFAST-CRISPR”, as an affordable, rapid and high-precision molecular diagnostic means for SARS-CoV-2 detection. The herein proposed “sample-to-answer” platform integrates RNA extraction, amplification and CRISPR-Cas-based detection with lateral flow readout in one device. The microscale dimensions of the device containing immiscible liquids, coupled with the use of silica paramagnetic beads and GuHCl, streamline sample preparation, including RNA concentration, extraction and purification, in 15 min with minimal hands-on steps. By combining RT-LAMP with CRISPR-Cas12 assays targeting the nucleoprotein (N) gene, visual identification of ≥ 470 copies mL-1 genomic SARS-CoV-2 samples was achieved in 45 min, with no cross-reactivity towards HCoV-OC43 nor H1N1. On-chip assays showed the ability to isolate and detect SARS-CoV-2 from 1,000 genome copies mL-1 of replication-deficient viral particles in 1 h. This simple, affordable and integrated platform demonstrated a visual, faster, and yet specificity and sensitivity-comparable alternative to the costly gold-standard RT-PCR assay, requiring only a simple heating source. Further investigations on multiplexing and direct interfacing of the accessible Swan-brand cigarette filter for saliva sample collection could provide a complete work flow for COVID-19 diagnostics from saliva samples suitable for low-resource settings.
Consumers’ lodging intentions during a pandemic: empirical insights for crisis management practices based on protection motivation theory and expectancy theory
Authors: Fan Alei , Kline Sheryl F. , Liu Yiran , Byrd Karen 
Published: January 2022

Purpose
Drawing on protection motivation theory (PMT) and expectancy theory, this study aims to investigate consumers’ lodging consumption intentions during a pandemic crisis.

Design/methodology/approach
The research survey was conducted during the ongoing COVID-19 pandemic (August, 2020) in the USA to investigate consumers’ lodging intentions amidst the pandemic crisis. PLS-SEM and multiple regression were conducted to explore answers to proposed research questions.

Findings
The research finds that, during the pandemic crisis, consumers’ lodging consumption intentions are subject to both their internal protection motivation evaluations and the external prevention practices implemented by the lodging facilities regardless of property types and travel purposes. Notably, the research finds that consumers are willing to make efforts and pay extra for a safe stay at lodging facilities.

Research limitations/implications
This research contributes to the literature regarding the applications of PMT and expectancy theory from a crisis management perspective, and it provides implications and guidelines to the crisis management practices in the lodging industry.

Originality/value
The current research examines the specific protection motivation appraisal factors and prevention practices significantly impacting consumers’ decisions in terms of willingness to stay at various lodging facilities (hotels and non-hotel homestay/short-term rental properties) for different purposes (business and leisure) and to pay premiums for a safe stay.
The effect of investor sentiment and the structure of shareholder ownership on corporate investment
Authors: Li Hui , Grundy Bruce 
Published: January 2022

Purpose This paper aims to investigate the relations amongst investor sentiment, the structure of shareholder ownership and corporate investment.Design/methodology/approach This paper develops a theoretical model, proposes hypotheses based on the predictions of the model and conducts empirical tests. The primary method is panel regression with fixed effects. The sample covers the US data for the period between 1980 and 2018.Findings This paper finds that firms with a higher proportion of retail investors invest more than otherwise similar firms. In the low-sentiment periods, the financially constrained firms invest less than the non-financially constraint firms. The positive effect of residual retail ownership on the investment level is higher for firms with a higher idiosyncratic risk.Practical implications The results suggest that larger share ownership of the relatively informed institutional investors may serve as a mechanism that could reduce the degree of overinvestment caused by higher investor sentiment and the over-optimistic of the relatively uninformed investors.Originality/value This paper provides an incremental theoretical and empirical contribution to the relations amongst investor sentiment, corporate investment and the structure of shareholder ownership.
Changes in knowledge coupling and innovation performance: the moderation effect of network cohesion
Authors: Jin Na , Yang Naiding , Fawad Sharif Sayed Muhammad , Li Ruimeng 
Published: January 2022

Purpose
Collaborative research and development have remained a pertinent mechanism for conducting technological innovations. With the lens of knowledge-based view (KBV), this study aims to examine the role of changes in knowledge couplings and network cohesion to elevate innovation performance.

Design/methodology/approach
Data analysis has been performed on 53,459 patents through regression analysis with random effects. These independent and joint patents are extracted from Derwent Innovation Database.

Findings
Findings explicate that change in external existing or existing and new knowledge couplings have inverted U-shaped effects on a firm’s innovation performance. Changes in internal existing or existing and new knowledge couplings have direct positive effects on firm’s innovation performance. The moderation effect of network cohesion flattens the inverted U-shaped effect of external new and existing knowledge coupling, whereas it has no significant effect on external existing knowledge coupling. Network cohesion further elevates the effects of internal knowledge couplings – existing or existing and new.

Research limitations/implications
This study theoretically contributes to KBV and innovation management literature by highlighting the scope of changes in internal and external knowledge couplings and subsequent output. Network cohesion flattens the curviness of changes in external new and existing knowledge couplings, which is a contribution to strategic management literature.

Practical implications
Organizations need to carefully manage changes in knowledge couplings and ensure their benefits (obtain new knowledge domain or new combination) outweigh liabilities (damages to organizational routines or increase in collaboration costs). Managers must consider four kinds of knowledge coupling changes along with developing network cohesion as an R&D strategy.

Originality/value
This study is one of its types to flatten the curve through network cohesion. This study divided the changes in knowledge coupling into four types and two dimensions; external existing and new and existing knowledge couplings and internal existing and new and existing knowledge couplings.