bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic and phenotypic trait variation of the opportunistic human pathogen Aspergillus flavus and its non-pathogenic close relatives
Authors: Hatmaker E. Anne , Rangel-Grimaldo Manuel , Raja Huzefa A. , Pourhadi Hadi , Knowles Sonja L. , Fuller Kevin , Adams Emily M. , Lightfoot Jorge D. , Bastos Rafael W. , Goldman Gustavo H. , Oberlies Nicholas H. , Rokas Antonis 
Published: July 2022

ABSTRACTFungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus is a causative agent of both aspergillosis and fungal keratitis infections, but species closely related to A. flavus are not considered clinically relevant. To study the evolution of A. flavus pathogenicity, we examined genomic and phenotypic traits of two strains of A. flavus and three closely related non- pathogenic species: Aspergillus arachidicola (two strains), Aspergillus parasiticus (two strains), and Aspergillus nomiae (one strain). We identified over 3,000 orthologous proteins unique to A. flavus, including seven biosynthetic gene clusters present in A. flavus strains and absent in the three non-pathogenic species. We chose to characterize secondary metabolite production for all seven strains under two clinically relevant conditions, temperature and salt concentration. Temperature impacted metabolite production in all species. Conversely, we found a lack of impact of salinity on secondary metabolite production. Strains of the same species produced different metabolites. Growth under stress conditions revealed additional heterogeneity within species. Using the invertebrate model of fungal disease Galleria mellonella, we found virulence of strains of the same species varied widely, and A. flavus strains were not more virulent than strains of the non-pathogenic species. In a murine model of fungal keratitis, we observed significantly lower disease severity and corneal thickness for A. arachidicola compared to other species at 48 hrs, but not at 72 hrs. Our work identifies key phenotypic, chemical, and genomic similarities and differences between the opportunistic human pathogen A. flavus and its non-pathogenic relatives.
Conserved Link between Catalytic Site Interactions and Global Conformation in P-loop Enzymes
Authors: Hajredini Fatlum , Ghose Ranajeet 
Published: July 2022

AbstractP-loop enzymes, ubiquitous in all of life’s domains and viruses, comprise a monophyletic group with pre-LUCA origins that have differentiated into several three-layered α/β/α− sandwich domain families utilizing a basic β− loop−α−β structural module housing conserved nucleotide-binding Walker-A and Walker-B sequences. We have analyzed a large dataset of P-loop enzyme structures representing both their KG and ASCE branches as proxies for their sampled conformational landscapes. We developed a novel framework to correlate global conformations and local catalytic site geometry, specifically involving the Walker motifs, to identify conserved signatures despite substantial structural and functional diversity. Our results suggest that P-loop enzymes populate global states broadly classifiable as open or closed. In the closed states, that share similar overall geometries irrespective of family, key catalytic site residues are aligned to optimally engage the critical Mg2+ ion suggesting compatibility with the chemical step. These catalytic site interactions are disrupted in the open states resulting in the loss of the Mg2+- coordinating ability yielding conformations incapable of chemistry. In contrast to the closed states, open states are highly diverse, and this variability is facilitated by differential coupling of specific residues that are part of, or spatially proximal to, the Walker motifs with the clade-specific tertiary fold. We suggest that an essential feature in the activation and nucleotide exchange processes for all P-loop enzymes is the universal coupling between global closure and local reorganization of the catalytic site for efficient coordination of Mg2+ that carries a tightly associated cargo, the substrate NTP.
Maximizing CRISPRi efficacy and accessibility with dual-sgRNA libraries and optimal effectors
Authors: Replogle Joseph M. , Bonnar Jessica L. , Pogson Angela N. , Liem Christina R. , Maier Nolan K. , Ding Yufang , Russell Baylee J. , Wang Xingren , Leng Kun , Guna Alina , Norman Thomas M. , Pak Ryan A. , Ramos Daniel M. , Ward Michael E. , Gilbert Luke A. , Kampmann Martin , Weissman Jonathan S. , Jost Marco 
Published: July 2022

AbstractCRISPR interference (CRISPRi) enables programmable, reversible, and titratable repression of gene expression (knockdown) in mammalian cells. Initial CRISPRi-mediated genetic screens have showcased the potential to address basic questions in cell biology, genetics, and biotechnology, but wider deployment of CRISPRi screening has been constrained by the large size of single guide RNA (sgRNA) libraries and challenges in generating cell models with consistent CRISPRi-mediated knockdown. Here, we present next-generation CRISPRi sgRNA libraries and effector expression constructs that enable strong and consistent knockdown across mammalian cell models. First, we combine empirical sgRNA selection with a dual-sgRNA library design to generate an ultra-compact (1-3 elements per gene), highly active CRISPRi sgRNA library. Next, we rigorously compare CRISPRi effectors to show that the recently published Zim3-dCas9 provides the best balance between strong on-target knockdown and minimal nonspecific effects on cell growth or the transcriptome. Finally, we engineer a suite of cell lines with stable expression of Zim3-dCas9 and robust on-target knockdown. Our results and publicly available reagents establish best practices for CRISPRi genetic screening.
Mutational spectra analysis reveals bacterial niche and transmission routes
Authors: Ruis Christopher , Weimann Aaron , Tonkin-Hill Gerry , Pandurangan Arun Prasad , Matuszewska Marta , Murray Gemma G. R. , Lévesque Roger C. , Blundell Tom L. , Floto R. Andres , Parkhill Julian 
Published: July 2022

AbstractAs observed in cancers, individual mutagens and defects in DNA repair create distinctive mutational signatures that combine to form context-specific spectra within cells. We reasoned that similar processes must occur in bacterial lineages, potentially allowing decomposition analysis to identify disrupted DNA repair processes and niche-specific mutagen exposure. Here we reconstructed mutational spectra for 84 clades from 31 diverse bacterial species, assigned signatures to specific DNA repair pathways using hypermutator lineages, and, by comparing mutational spectra of clades from different environmental and biological locations, extracted reproducible niche-associated mutational signatures. We show that mutational spectra can predict general and specific bacterial niches and therefore reveal the site of infection and types of transmission routes for established and emergent human bacterial pathogens.One sentence summaryVariable mutagen exposure and DNA repair drive differential mutational spectra between bacteria and enable niche inference
Differences in single-motor and multi-motor motility properties across the kinesin-6 family
Authors: Poulos Andrew , Budaitis Breane G. , Verhey Kristen J. 
Published: July 2022

AbstractKinesin motor proteins are responsible for orchestrating a variety of microtubule-based processes including intracellular transport, cell division, cytoskeletal organization, and cilium function. During cell division, members of the kinesin-6 family play critical roles in anaphase and cytokinesis, however little is known about their motility properties. We find that truncated versions of MKLP1 (HsKIF23), MKLP2 (HsKIF20A), andHsKIF20B predominately display non-processive behavior as single molecules although slow, processive motility was occasionally observed, most prominently for MKLP2. Despite their non-processive nature, all kinesin-6 proteins were able to work in teams to drive microtubule gliding. MKLP1 and KIF20B were also able to work in teams to drive robust transport of both peroxisomes, a low-load cargo, and Golgi, a high-load cargo, in cells. In contrast, MKLP2 showed minimal transport of peroxisomes and was unable to drive Golgi dispersion. These results indicate that while all three mammalian kinesin-6 motor proteins are generally non-processive as single motors, they differ in their ability to work in teams and generate forces needed to drive cargo transport in cells.
Molecular Neurobiology of Loss
Authors: Smail Marissa A. , Smith Brittany L. , Shukla Rammohan , Alganem Khaled , Eby Hunter M. , Bollinger Justin L. , Parikh Ria K. , Chambers James B. , Reigle James K. , Moloney Rachel D. , Nawreen Nawshaba , Wohleb Eric S. , Pantazopoulos Harry , McCullumsmith Robert E. , Herman James P. 
Published: July 2022

ABSTRACTPsychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an enrichment removal (ER) paradigm in rats. A comprehensive multi-omics investigation of the basolateral amygdala (BLA) revealed alterations in microglia and extracellular matrix (ECM). Follow-up studies indicated that ER decreased microglia size, complexity, and phagocytosis, suggesting reduced immune surveillance. Loss also substantially increased ECM coverage, specifically targeting perineuronal nets surrounding parvalbumin interneurons, suggesting decreased plasticity and increased inhibition in the BLA following loss. Behavioral analyses suggest that these molecular effects are linked to impaired BLA salience evaluation, reflecting emotional blunting observed in human loss. These loss-like behaviors could be rescued by depleting BLA ECM during removal, helping us understand the mechanisms underlying loss and revealing novel molecular targets to ameliorate its impact.
Cortical patterns shift from sequence feature separation during planning to integration during motor execution
Authors: Yewbrey Rhys , Mantziara Myrto , Kornysheva Katja 
Published: July 2022

AbstractPerforming sequences of movements from memory and adapting them to changing task demands is a hallmark of skilled human behaviour, from handwriting to playing a musical instrument. Prior studies showed a fine-grained tuning of cortical primary motor, premotor, and parietal regions to motor sequences – from the low-level specification of individual movements to high-level sequence features like sequence order and timing. However, it is not known how tuning in these regions unfolds dynamically across planning and execution. To address this, we trained 24 healthy right-handed participants to produce four five-element finger press sequences with a particular finger order and timing structure in a delayed sequence production paradigm entirely from memory. Local cortical fMRI patterns during preparation and production phases were extracted from separate ‘No-Go’ and ‘Go’ trials, respectively, to tease out activity related to these peri-movement phases. During sequence planning, premotor and parietal areas increased tuning to movement order and timing, irrespective of their combinations. In contrast, patterns reflecting the unique integration of sequence features emerged in these regions during execution only, alongside timing-specific tuning in the ventral premotor, supplementary motor, and superior parietal areas. This was in line with the participants’ behavioural transfer of trained timing, but not of order to new sequence feature combinations. Our findings suggest a general neural state shift from high-level feature separation to low-level feature integration within cortical regions for movement execution. Recompiling sequence features trial-by-trial during planning may enable flexible last-minute adjustment before movement initiation.
Within-species differences in vocal production learning in a songbird are associated with differences in flexible rhythm pattern perception
Authors: Rouse Andrew A. , Patel Aniruddh D. , Wainapel Samantha , Kao Mimi H. 
Published: July 2022

AbstractHumans readily recognize a familiar rhythmic pattern, such as isochrony (equal timing between events) across a wide range of rates. This ability reflects a facility with perceiving the relative timing of events, not just absolute interval durations. Several lines of evidence suggest that this ability is supported by precise temporal predictions that arise from forebrain auditory-motor interactions. We have shown previously that male zebra finches, which possess specialized auditory-motor networks and communicate with rhythmically patterned sequences, share our ability to recognize isochrony independent of rate. To test the hypothesis that flexible rhythm pattern perception is linked to vocal learning, we ask whether female zebra finches, which do not learn to sing, can also recognize global temporal patterns. We find that non-singing females can flexibly recognize isochrony but perform slightly worse than males on average. These findings are consistent with recent work showing that while females have reduced forebrain song regions, the overall network connectivity of vocal premotor regions is similar to that in males and supports predictions of upcoming events. Comparative studies of male and female songbirds thus offer an opportunity to study how individual differences in auditory-motor connectivity influence perception of relative timing, a hallmark of human music perception.
A synthesized retail brand personality framework: a cross-cultural study of Taiwan and the United States
Authors: Kuo Ya-Hui , Wu Pei-Chiang , Ahn Sun Young 
Published: July 2022

PurposeThe purpose of this study was to develop a synthesized retail brand personality scale (RBPS) framework across retail formats. This research also addresses cultural differences by applying an emic-etic approach to scale development with United States (US) and Taiwanese samples.Design/methodology/approachAfter two focus group interviews and a pretest were conducted in both Taiwan and the US, a main test was conducted on consumer samples in Taiwan (N = 412) and in the US (N = 411). Confirmatory factor analysis was used to develop a valid, reliable RBPS.FindingsThe results revealed that sincerity and sophistication are comparable dimensions to those in the brand personality scale (BPS), and unpleasantness, traditionalism, enthusiasm, antagonism and innovativeness were found to be unique dimensions for retail brands. The findings also indicated that sincerity, unpleasantness and traditionalism are common dimensions across cultures, whereas innovativeness, sophistication and antagonism are culture-specific dimensions in the US, whereas enthusiasm is a specific dimension in Taiwan.Originality/valueTo the best of authors’ knowledge, this study is the first to develop a synthesized scale of retail brand personality that compares the identified dimensions to Aaker's (1997) BPS and includes an emic-etic approach. This research contributes to the branding literature and international marketing field, and has implications for retail practitioners.
The impact of COVID-19 lockdown on audit fees and audit delay: international evidence
Authors: Harjoto Maretno A. , Laksmana Indrarini 
Published: July 2022

Purpose
The purpose of this study is to examine the impact of the 2020 COVID-19 lockdown on the audit fees and audit delay of audit client firms located in 52 countries and audit firm offices located in 40 countries.

Design/methodology/approach
Using archival audit data from Audit Analytics in the fiscal year 2020, this study examines the impact of the length of COVID-19 lockdown and other public health restrictions, measured by the stringency index (Hale et al., 2021), on audit fees and audit delay using a multivariate regression analysis.

Findings
Based on a sample of 2,726 US firms and 718 non-US firms from 51 different countries outside the USA and audit firm offices in 40 countries during the fiscal year 2020, the authors find that the COVID-19 lockdown and public health restrictions increase audit fees and audit delay. However, non-US firms experience longer audit delay because of the lockdown than their US counterparts. In addition, longer lockdown and greater restrictions increase the audit fees and audit delay of non-US firms with high audit risk at a greater rate than those of US firms with high audit risk.

Practical implications
The results of this study suggest that auditors increase audit fees and have longer audit delay when facing more COVID-19 restrictions. Increased audit fees and audit delay are likely to result from higher perceived audit risk and, consequently, additional audit effort to design new procedures, train staff to use the new procedures and implement them amid the pandemic restrictions. The impact of COVID lockdown and restrictions on audit fees and audit delay are more pronounced for non-US firms with greater audit risk. The results of this study suggest that audit firms should quickly adapt to the evolving audit, risk and financial landscape created by the pandemic.

Originality/value
Using archival audit data and large sample size, this study provides the first empirical evidence of the impact of lockdown and public health restrictions during the first wave of COVID-19 outbreak on audit processes as measured with audit fees and audit delay.
Public debt-investment nexus: the significance of investment-generation policy in West Africa
Authors: Fagbemi Fisayo , Adeosun Opeoluwa Adeniyi 
Published: July 2022

PurposeThe main goal of the study is to explore the long run relationship between public debt and domestic investment in West Africa. Essentially, a study of this nature is to proffer major inroads into addressing low investment levels plaguing the region and securing critical fiscal policy measures.Design/methodology/approachThe study examines the long-run relationship between public debt and domestic investment in 13 West African countries between 1986 and 2018 with the use of Panel Dynamic Least Squares (DOLS) and Panel Fully Modified Least Squares (FMOLS), and causality test based on Toda and Yamamoto.FindingsPublic debt (% of GDP) and external debt stocks have an insignificant effect on domestic investment in the long run, suggesting the negligible effect of public debt on the level of investments in the region. Further evidence shows that domestic investment Granger causes public debt indicators, implying that there is unidirectional causality. This suggests that any investment-generation policy could engender a rise in public borrowing, although such public loans might not be effective when there is pervasive mismanagement of public funds, as public debts need to be well managed for ensuring improved investment.Research limitations/implicationsThe study suggests that maintaining a strong and effective debt-investment nexus requires fiscal consolidation efforts across countries, as such could lead to enhanced institutional capacity and sustainable investment-generation policy.Originality/valueSince panel regression techniques used by the previous studies (Fixed and Random effects) could be susceptible to possible statistical errors due to endogeneity issue and might not be well suited for explaining long-run effect or capturing the part of investment sustainability, their conclusions could be misleading and remain untenable in West Africa' s context. Hence, the study adopts techniques (DOLS and FMOLS) which could account for endogeneity issue and provide better elucidations for long-term effects.
Service brand avoidance in business-to-business relationships
Authors: Otoo Dorothea Sekyiwa , Odoom Raphael , Braimah Stephen Mahama 
Published: July 2022

Purpose
This paper aims to examine the drivers of service brand avoidance in business-to-business relationships within an emerging economy setting.

Design/methodology/approach
This study used an explanatory research design with a quantitative approach. Data was obtained through self-administered questionnaires and a uniform resource locator via Google Forms. The hypothesised relationships were analysed using the partial least squares structural equation modelling technique.

Findings
This research reveals that unmet expectations, symbolic incongruence and failed communications directly influence brand avoidance, while ideological incompatibility significantly impacts symbolic incongruence. In contrast, unacceptable trade-offs and ideological incompatibility do not directly influence brand avoidance in B2B relationships.

Research limitations/implications
Future studies may consider examining brand avoidance by business clients within other specific industries and its impact on co-branding agreements.

Originality/value
This study provides empirical evidence of drivers of service brand avoidance within business markets from an emerging economy perspective.
CCP committees, worker benefits and firm performance: empirical evidence from Chinese private firms
Authors: Long Cheryl , Yang Jin 
Published: July 2022

PurposeWith an increasing number of Chinese private firms establishing primary level CPC Party committees, it is important to study the role of Party organizations in these firms. Using a nationwide survey of private firms in 2006, we empirically study the firm-level CCP committee's effect on workers' benefits and firm performance.Design/methodology/approachTo overcome the potential endogeneity, we employ the regression discontinuity approach by utilizing the following rule from the Constitution of the CCP: Primary party committees should be established in any basic work unit with more than 3 full party members.FindingsOur empirical results show that party committees in private firms have positive and statistically significant effects on many types of workers' benefits, including pension, unemployment insurance and workplace safety.Originality/valueThis paper highlights CCP committees as an important alternative mechanism in coordinating labor relationships in China when formal labor protecting institutions are weak.
Vertically versus horizontally differentiated information disclosure in travel live streams – the role of sensory imagery
Authors: Sun Jin , Yang Jingshu , Wang Yonggui 
Published: July 2022

PurposeThis paper aims to investigate the differential effects of vertical attributes and horizontal attributes on visit intention under proximal and distal sensory imagery in travel live streams.Design/methodology/approachThis research used a multimethod approach with four studies. Three designed experiments were first employed to prove casual relations of the hypothesized relations. Then, a structural model provided a new sample of the framework.FindingsThe results suggest that visit intention is higher when vertical (vs horizontal) attributes are associated with proximal (vs distal) sensory imagery. Physical presence mediates the interaction effects between attribute type and sensory imagery on visit intention.Practical implicationsThe finding offers suggestions for multilateral information providers' capability of real-time advertising, seller-focused technology development and proactive relationship management with potential consumers.Originality/valuePrevious study is less sufficient to describe consumers' traveling interactivities in live-streaming media, where streamers are capable of modifying attribute-based messages and sensory modalities. Rather than focusing on imagery as a comprehensive modality or visual-dominated imagery, this study examines the interaction effects between attribute type and sensory imagery on visit intention. Drawing on reason-based choice and distance-on-distance theories, the finding enriches the evaluation of the effectiveness of live-streaming marketing across varying sensory interactions.