bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOXO1 repressesSprouty2andSprouty4expression in endothelial cells to promote arterial specification and vascular remodeling in the mouse yolk sac
Authors: Li-Villarreal Nanbing , Wong Rebecca Lee Yean , Garcia Monica D. , Udan Ryan S. , Poché Ross A. , Rasmussen Tara L. , Rhyner Alexander M. , Wythe Joshua D. , Dickinson Mary E. 
Published: September 2021

ABSTRACTThe establishment of a functional circulatory system is required for post-implantation development during murine embryogenesis. Previous studies in loss of function mouse models have shown that FOXO1, a Forkhead family transcription factor, is required for yolk sac vascular remodeling and survival beyond embryonic day (E) 11. Here, we demonstrate that loss ofFoxO1in E8.25 endothelial cells results in increasedSprouty2andSprouty4transcripts, reduced expression of arterial genes, and decreasedFlk1/Vegfr2mRNA levels without affecting overall endothelial cell identity, survival, or proliferation. Using aDll4-BAC-nlacZreporter line, we found that one of the earliest expressed arterial genes,Delta like 4(Dll4), is significantly reduced in the yolk sac ofFoxO1mutants without being substantially affected in the embryo proper. We show that in the yolk sac, FOXO1 not only binds directly to a subset of previously identifiedSprouty2gene regulatory elements (GREs), as well as newly identified, evolutionarily conservedSprouty4GREs, but can also repress their expression. Additionally, over expression ofSprouty4in transient transgenic embryos largely recapitulates reduced expression of arterial genes seen in endothelialFoxO1mutant mouse embryos. Together, these data reveal a novel role for FOXO1 as a key early transcriptional repressor controlling both pre-flow arterial specification and subsequent vessel remodeling within the murine yolk sac.
Distinct stress-dependent signatures of cellular and extracellular tRNA-derived small RNAs (tDRs)
Authors: Li Guoping , Manning Aidan , Bagi Alex , Yang Xinyu , Howard Jonathan , Chan Patricia P. , Sweeney Thadryan , Li Haobo , Laurent Brice D. , Kontaridis Maria I. , Laurent Louise C. , Van Keuren-Jensen Kendall , Aranki Sary F. , Muehlschlegel Jochen , Kitchen Robert , Lowe Todd M. , Das Saumya 
Published: September 2021

SUMMARYThe cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may yield novel biomarkers for different diseases, and potentially identify key signaling pathways important for disease progression. tRNAs and tRNA-derived small RNAs (tDRs) comprise one of the most abundant RNA species in cells and have been associated with cellular stress responses. The presence of RNA modifications on tDRs has been an obstacle for accurately identifying tDRs with conventional small RNA sequencing. Here, we use AlkB-facilitated methylation sequencing (ARM-seq) to uncover a comprehensive landscape of cellular and extracellular tDR expression in a variety of human and rat cells during common stress responses, including nutritional deprivation, hypoxia, and oxidative stress. We found that extracellular tDRs have a distinct fragmentation signature with a predominant length of 31-33 nts and a highly specific termination position when compared with intracellular tDRs. Importantly, we found these signatures are better discriminators of different cellular stress responses compared to extracellular miRNAs. Distinct extracellular tDR signatures for each profiled stressor are elucidated in four different types of cells. This distinct extracellular tDR fragmentation pattern is also noted in plasma extracellular RNAs from patients on cardiopulmonary bypass. The observed overlap of these patient tDR signatures with the signatures of nutritional deprivation and oxidative stress in our cellular models provides preliminary in vivo corroboration of our findings and demonstrates the potential to establish novel extracellular tDR biomarkers in human disease models.
The human disease geneCLEC16Aencodes an intrinsically disordered protein region required for mitochondrial quality control
Authors: Gingerich Morgan A. , Liu Xueying , Chai Biaoxin , Pearson Gemma L. , Vincent Michael P. , Stromer Tracy , Zhu Jie , Sidarala Vaibhav , Renberg Aaron , Sahu Debashish , Klionsky Daniel J. , Schnell Santiago , Soleimanpour Scott A. 
Published: September 2021

ABSTRACTCLEC16A regulates mitochondrial health through mitophagy and is associated with over 20 human diseases. While CLEC16A has ubiquitin ligase activity, the key structural and functional regions of CLEC16A, and their relevance for human disease, remain unknown. Here, we report that a disease-associated CLEC16A variant lacks a C-terminal intrinsically disordered protein region (IDPR) that is critical for mitochondrial quality control. Using carbon detect NMR, we find that the CLEC16A C terminus lacks secondary structure, validating the presence of an IDPR. Loss of the CLEC16A C-terminal IDPRin vivoimpairs pancreatic β-cell mitophagy, mitochondrial function, and glucose-stimulated insulin secretion, ultimately causing glucose intolerance. Deletion of the CLEC16A C-terminal IDPR increases its self-ubiquitination and destabilizes CLEC16A, thus impairing formation of a critical CLEC16A-dependent mitophagy complex. Importantly, CLEC16A stability is dependent on proline bias within the C-terminal IDPR, but not amino acid sequence order or charge. Together, we clarify how an IDPR in CLEC16A prevents diabetes, thus implicating the disruption of IDPRs as novel pathological contributors to diabetes and other CLEC16A-associated diseases.
Transposon Screen of Surface Accessibility inS. aureus
Authors: Ferraro Noel J. , Pires Marcos M. 
Published: September 2021

AbstractBacterial cell walls represent one of the most prominent targets of antibacterial agents. These agents include natural products (e.g., vancomycin) and proteins stemming from the innate immune system (e.g., peptidoglycan-recognition proteins and lysostaphin). Among bacterial pathogens that infect humans,Staphylococcus aureus(S. aureus) continues to impose a tremendous healthcare burden across the globe.S. aureushas evolved countermeasures that can directly restrict the accessibility of innate immune proteins, effectively protecting itself from threats that target key cell well components. We recently described a novel assay that directly reports on the accessibility of molecules to the peptidoglycan layer within the bacterial cell wall ofS. aureus. The assay relies on site-specific chemical remodeling of the peptidoglycan with a biorthogonal handle. Here, we disclose the application of our assay to a screen of a nonredundant transposon mutant library for susceptibility of the peptidoglycan layer with the goal of identifying genes that contribute to the control of cell surface accessibility. We discovered several genes that resulted in higher accessibility levels to the peptidoglycan layer and showed that these genes modulate sensitivity to lysostaphin. These results indicate that this assay platform can be leveraged to gain further insight into the biology of bacterial cell surfaces.Table of Contents Figure
Adaptation and phenotypic diversification ofBacillus thuringiensis407 biofilm are accompanied by a fuzzy spreader morphotype
Authors: Lin Yicen , Maróti Gergely , Strube Mikael Lenz , Kovács Ákos T. 
Published: September 2021

AbstractBacillus cereusgroup (Bacillus cereus sensu lato) has a diverse ecology, including various species that produce biofilms on abiotic and biotic surfaces. While genetic and morphological diversification enable the adaptation of multicellular communities, this area remains largely unknown in theBacillus cereusgroup. In this work, we dissected the experimental evolution ofBacillus thuringiensis407 Cry-during continuous recolonization of plastic beads. We observed the evolution of a distinct colony morphotype that we named fuzzy spreader (FS) variant. Most multicellular traits of the FS variant displayed higher competitive ability versus the ancestral strain, suggesting an important role for diversification in the adaptation ofB. thuringiensisto the biofilm lifestyle. Further genetic characterization of FS variant revealed the disruption of a guanylyltransferase gene by an insertion sequence (IS) element, which could be similarly observed in the genome of a natural isolate. The evolved FS and the deletion mutant in the guanylyltransferase gene (Bt407ΔrfbM) displayed similarly altered aggregation and hydrophobicity compared to the ancestor strain, suggesting that adaptation process highly depends on the physical adhesive forces.
Assessing the effectiveness of honey bee pollinators for cultivated blueberries in South Africa
Authors: Martin Keanu , Anderson Bruce , Minnaar Corneile , de Jager Marinus L 
Published: September 2021

AbstractGlobally, agricultural crops are often dependent on insect pollination. Blueberries are an example of such a crop and owing to their proposed health benefits they are grown around the world, including locations where their native bumble bee pollinators do not occur. In the absence of bumble bees, blueberry pollination in South Africa and many other parts of the non-native, commercial range is performed primarily by honey bees. Despite this, the effectiveness of honey bee pollination on blueberries remains understudied. This study determined the effect of honey bee pollination on components of fruit yield (fruit set and mass) of five blueberry varieties that are extensively planted in South Africa. For each variety, two metrics were calculated: 1) the benefit of bees — a comparison of fruit yields after exposure to honey bees and fruit yields after honey bee exclusion, 2) the pollination deficit — the difference in yield between hand pollination (maximum yield potential) and yields after exposure to honey bee pollinators. Honey bee pollination consistently resulted in improved yields, although the magnitude of this improvement (i.e., the benefit of bees) was dependent on the variety considered. Similarly, the pollination deficit also varied considerably across varieties and while some varieties appeared to perform close to maximum potential (small pollination deficit), others yielded well below their maximum potential under honey bee pollination. This study demonstrates that honey bees are functional pollinators of blueberries in areas where native blueberry pollinators are absent. However, in such areas, it is important that special focus be given to selecting blueberry varieties that perform well with honey bees as their sole pollinator. Further research is necessary to determine how the pollination deficit of blueberry varieties can be decreased as well as how to increase the effectiveness of honey bee pollination.
A cytoplasmic protein kinase in Chlamydomonas couples engagement of ciliary receptors to rapid cellular responses
Authors: Awasthi Mayanka , Ranjan Peeyush , Kelterborn Simon , Hegemann Peter , Snell William J. 
Published: September 2021

AbstractThe principal function of the primary cilium is to convert cues from the extracellular milieu into changes in cyclic nucleotide concentration and cytoplasmic responses, but fundamental questions remain about the mechanisms of transmission of cilium-to-cytoplasm signals. During fertilization in Chlamydomonas reinhardtii, ciliary adhesion between plus and minus gametes triggers an immediate ∼10-fold increase in cellular cAMP and activation for cell fusion. Here, we identify Gamete-Specific Protein Kinase (GSPK) as an essential link between cilary receptor engagement and gamete activation. The ciiary adhesion-induced increase in cAMP and cell fusion are severely impaired in gspk mutants but fusion is rescued by a cell-permeable form of cAMP, indicating that GSPK functions upstream of the cAMP increase. GSPK is cytoplasmic, and, remarkably, the entire cellular complement is phosphorylated in less than 60 seconds after ciliary contact. Thus, a cytoplasmic protein kinase rapidly converts a ciliary membrane cue into a global cellular response.
The m6A reader YTHDC2 is essential for escape from KSHV SOX-induced RNA decay
Authors: Macveigh-Fierro Daniel , Cicerchia Angelina , Cadorette Ashley , Sharma Vasudha , Muller Mandy 
Published: September 2021

AbstractThe role m6A modifications have increasingly been associated with diverse set of roles in modulating viruses and influencing the outcomes of viral infection. Here we report that the landscape of m6A deposition is drastically shifted during KSHV (Kaposi Sarcoma Associated herpesvirus) lytic infection for both viral and host transcripts. In line with previous reports, we also saw an overall decrease in host methylation in favor of viral mRNA along with 5’ hypomethylation and 3’ hypermethylation. During KSHV lytic infection, a major shift in overall mRNA abundance is driven by the viral endoribonuclease SOX, which induces the decay of greater than 70% of transcripts. Here, we reveal that Interlukin-6 (IL-6) mRNA, a well-characterized SOX-resistant transcript, is m6A modified during lytic infection. Furthermore, we show that this modification falls within the IL-6 SOX Resistance Element (SRE), an RNA element in IL-6 3’ UTR that was previously shown to be sufficient for protection from SOX cleavage. We show that the presence of this m6A modification is essential to confer SOX resistance to the IL-6 mRNA. We next show that this modification recruits the m6A reader YTHDC2 and found that YTHDC2 is necessary for the escape of the IL-6 transcript. These results shed light on how the host cell has evolved to use RNA modifications to circumvent viral manipulation of RNA fate during KSHV infection.
MAR1 links membrane adhesion to membrane merger during cell-cell fusion in Chlamydomonas
Authors: Pinello Jennifer F. , Liu Yanjie , Snell William J. 
Published: September 2021

SummaryUnion of two gametes to form a zygote is a defining event in the life of sexual eukaryotes, yet the mechanisms that underlie cell-cell fusion during fertilization remain poorly characterized. Here, in studies of fertilization in the green alga, Chlamydomonas, we report identification of a membrane protein on minus gametes, Minus Adhesion Receptor 1 (MAR1), that is essential for the membrane attachment with plus gametes that immediately precedes lipid bilayer merger. We show that MAR1 forms a receptor pair with previously identified receptor FUS1 on plus gametes, whose ectodomain architecture we find is identical to a sperm adhesion protein conserved throughout plant lineages. Strikingly, before fusion, MAR1 is biochemically and functionally associated with the ancient, evolutionarily conserved eukaryotic class II fusion protein HAP2 on minus gametes. Thus, the integral membrane protein MAR1 provides a molecular link between membrane adhesion and bilayer merger during fertilization in Chlamydomonas.
Genomic evidence for divergent co-infections of SARS-CoV-2 lineages
Authors: Zhou Hang-Yu , Cheng Ye-Xiao , Xu Lin , Li Jia-Ying , Tao Chen-Yue , Ji Cheng-Yang , Han Na , Yang Rong , Li Yaling , Wu Aiping 
Published: September 2021

AbstractRecently, patients co-infected by two SARS-CoV-2 lineages have been sporadically reported. Concerns are raised because previous studies have demonstrated co-infection may contribute to the recombination of RNA viruses and cause severe clinic symptoms. In this study, we have estimated the compositional lineage(s), tendentiousness, and frequency of co-infection events in population from a large-scale genomic analysis for SARS-CoV-2 patients. SARS-CoV-2 lineage(s) infected in each sample have been recognized from the assignment of within-host site variations into lineage-defined feature variations by introducing a hypergeometric distribution method. Of all the 29,993 samples, 53 (~0.18%) co-infection events have been identified. Apart from 52 co-infections with two SARS-CoV-2 lineages, one sample with co-infections of three SARS-CoV-2 lineages was firstly identified. As expected, the co-infection events mainly happened in the regions where have co-existed more than two dominant SARS-CoV-2 lineages. However, co-infection of two sub-lineages in Delta lineage were detected as well. Our results provide a useful reference framework for the high throughput detecting of SARS-CoV-2 co-infection events in the Next Generation Sequencing (NGS) data. Although low in average rate, the co-infection events showed an increasing tendency with the increased diversity of SARS-CoV-2. And considering the large base of SARS-CoV-2 infections globally, co-infected patients would be a nonnegligible population. Thus, more clinical research is urgently needed on these patients.
Why won’t people speak up? Unpacking silence at work
Authors: Workman-Stark Angela 
Published: September 2021

Purpose
This paper examines employee silence, namely, the causes of silence and how it might be overcome.

Design/methodology/approach
Drawing from academic research and work with organizations, the author explains that workplace diversity is insufficient to guarantee the contributions of diverse voices. The author then provides an overview of why individuals choose to remain silent and explores aspects of organizational culture and climate that contribute to silencing behaviors. Finally, the author offers suggestions on how organizational leaders can overcome silence.

Findings
The findings suggest that employee voice can be activated through a psychologically safe working environment in which leaders adopt a learning mindset, practice humility, create opportunities for all team members to contribute, treat people with fairness and respect, and hold others accountable to do the same. The findings also indicate that leaders can support safe and inclusive working environments by challenging basic assumptions and accepting vulnerability.

Originality/value
This paper makes an important contribution to the field of organization development and change by providing suggestions for how organizations can address workplace concerns and enhance performance by removing the inhibitors of “employee voice”.
Sociotechnical factors and Industry 4.0: an integrative perspective for the adoption of smart manufacturing technologies
Authors: Marcon Érico , Soliman Marlon , Gerstlberger Wolfgang , Frank Alejandro G. 
Published: September 2021

PurposeAs the level of implementation of Industry 4.0 increases, misalignments between adopted technologies and organizational factors may result in benefits below expected. This paper aims to analyze how organizational factors can contribute to a higher level of adoption of Industry 4.0 technologies. The paper uses a sociotechnical perspective lens to achieve this aim.Design/methodology/approachUsing a sample of 231 manufacturing companies in Denmark, a leading country in Industry 4.0 readiness, the paper analyzes through cluster analysis and logistic regression whether the development of four sociotechnical dimensions – that is, Social, Technical, Work Organization and Environmental factors – in these companies can benefit the achievement of higher levels of Industry 4.0 technology adoption.FindingsThe results show that companies focused on the development of sociotechnical aspects generally present higher Industry 4.0 adoption levels. However, some sociotechnical factors are less supportive than others.Originality/valueBased on these results, practitioners can plan the adoption of advanced technologies, using a systemic organizational view. This study provides evidence on a growing field with few empirical studies available. The paper contributes by providing an analysis of a leading country in Industry 4.0 implementation, presenting a systemic view on technology adoption in the Industry 4.0 context.
The impact of Covid-19 on customer journeys: implications for interactive marketing
Authors: Kannan P.K. , Kulkarni Gauri 
Published: September 2021

PurposeThe Covid-19 pandemic and the related closures and lockdowns have changed how consumers shop for products and how they consume them. In this paper, the authors focus on how customers' journeys from the awareness stage down to purchase and loyalty stages have been impacted by the pandemic across different product categories and markets and how they affect the same post-pandemic. The authors propose directions for future research based on our analysis.Design/methodology/approachAnalyzing the components of customer utility, the authors provide the basis for the rapid shift towards online and digital touchpoints and the nature of emerging interactions between firms and consumers. The authors highlight those areas where changes could be permanent.FindingsThe authors show why some of the changes due to the Covid-19 pandemic could be permanent and irrevocable and what this implies for firms' strategies to acquire, retain, and grow their business with their customers.Originality/valueThe authors highlight why omnichannel strategies are the way for firms to thrive in the post-pandemic marketplace, and outline areas for future research that will allow researchers to examine how customer journeys will evolve post-pandemic.
Profiting from innovation in the aftermath of an economic crisis
Authors: Lichtenthaler Ulrich 
Published: September 2021

Purpose
The aim of this paper is to present systematically a variety of benefits from innovating in response to an economic crisis.

Design/methodology/approach
This is a conceptual paper that draws on prior conceptual and empirical studies, especially the innovation-based view of firm performance.

Findings
Many firms have cut their innovation expenditures in response to the COVID-19 crisis. However, the financial crisis in 2008/2009 has shown that these short-term cost savings may have severely negative consequences on competitiveness. Several innovation examples from the crisis due to the COVID-19 pandemic further indicate that companies may benefit from a variety of first-order innovations, which go considerably beyond product development. Consequently, researchers and executives need to consider the variety of innovation types beyond product development, and they further need to emphasize second-order innovations, which describe the dynamic transformation of innovation management.

Originality/value
Academics and practitioners need to put specific attention to the transformation of innovation processes at the beginning of a crisis because firms may have to redesign their innovation processes. This dynamic reconfiguration and realignment of innovation processes further is essential again if a crisis continues for a longer period, such as the crisis due to the coronavirus pandemic. For example, if a company currently does not respond to relevant trends, its competitive position will deteriorate because other companies will enter the market. If firms can afford to continue or strengthen the innovation activities, they may profit substantially after the crisis.