bluuebunny/crossref_metadata_2025_split huggingface dataset:
rRNA transcription is integral to liquid-liquid phase separation and maintenance of nucleolar structure
Authors: Dash Soma , Lamb Maureen C. , Lange Jeffrey J. , McKinney Mary C. , Tsuchiya Dai , Guo Fengli , Zhao Xia , Corbin Timothy J. , Kirkman MaryEllen , Delventhal Kym , Moore Emma L. , McKinney Sean , Shiang Rita , Trainor Paul A. 
Published: November 2022

SummaryBeginning with transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus, ribosome biogenesis is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis has been previously shown to affect nucleolar structure, yet the underlying mechanism is unknown. We generated loss-of-function mouse mutants of Pol I subunits,Polr1a, Polr1b, Polr1candPolr1d, thereby genetically inhibiting rRNA transcription and ribosome biogenesis. Pol I mutant embryos are preimplantation lethal and have fewer nucleoli. Using hiPSCs triple labeled for the three nucleolar compartments, we observe two phenotypes upon Pol I inhibition: a single condensed nucleolus, and fragmented nucleoli. We find that when rRNA transcription is inhibited, the viscosity of the granular compartment of the nucleolus is increased disrupting its liquid-liquid phase separation properties, which results in a condensed nucleolus. Taken together, our data suggests that Pol I function and rRNA transcription are required for maintaining nucleolar structure and integrity.
Impact of combinatorial histone modifications on acetyllysine recognition by the ATAD2 and ATAD2B bromodomains
Authors: Phillips Margaret , Malone Kiera L. , Boyle Brian W. , Montgomery Cameron , Kressy Isabelle A. , Joseph Faith M. , Bright Kathleen M. , Boyson Samuel P. , Chang Sunsik , Nix Jay C. , Young Nicolas L. , Jeffers Victoria , Frietze Seth E. , Glass Karen C. 
Published: November 2022

ABSTRACTThe ATPase family AAA+ domain containing 2 (ATAD2) protein, and its paralog ATAD2B, have a C-terminal bromodomain that functions as a ‘reader’ of acetylated lysine residues on histone proteins. Using a structure-function approach, we investigated the ability of the ATAD2 and ATAD2B bromodomains to select acetylated lysine among multiple histone post-translational modifications. Isothermal titration calorimetry experiments revealed that the ATAD2 and ATAD2B bromodomains selectively recognize distinct patterns of acetylated lysine residues on the N-terminal tails of histone proteins. Adjacent methylation or phosphorylation marks were found to either enhance or weaken the recognition of acetylated lysine by the ATAD2/B bromodomains. Complementary structural studies provide mechanistic insights into how residues within the bromodomain binding pocket coordinate the acetyllysine group in the context of adjacent post- translational modifications. Furthermore, we investigated how sequence changes in amino acids of the histone ligands, either as ‘onco’ mutations or as histone variants, impact the recognition of an adjacent acetylated lysine residue. In summary, our study highlights how the interplay between multiple combinations of histone modifications influences the ‘reader’ activity of the ATAD2 and ATAD2B bromodomains, resulting in distinct binding modes of the two bromodomains.KEY POINTSMultiple independent ATAD2 gene duplication events are evident during metazoan evolution, indicating expansion of functionality in the ATAD2 gene family and suggesting distinct functions for ATAD2 and ATAD2B.High-resolution structures of the ATAD2 and ATAD2B bromodomains in complex with their histone ligands demonstrate how multiple post-translational modifications are coordinated.Recognition of different subsets acetylated histone ligands by the ATAD2 and ATAD2B bromodomains is driven by unique features within the binding pockets of these paralogous proteins.Onco-histone mutations and histone variants that change the amino acid sequence of the histone tails modulate the ATAD2 and ATAD2B bromodomain activity.This study demonstrates how the combinatorial activity of multiple post- translational modifications forms a histone code and influences the recognition of acetylated lysine by bromodomain-containing proteins.
ShigellaIpaH9.8 limits GBP1-dependent LPS release from intracytosolic bacteria to suppress caspase-4 activation
Authors: Goers Lisa , Kim Kyungsub , Canning Patrick J. , Stedman Teagan C. , Mou Xiangyu , Ernst Nadja Heinz , Coers Jörn , Lesser Cammie F. 
Published: November 2022

AbstractPyroptosis is an inflammatory form of cell death induced upon the recognition of invading microbes. During an infection, pyroptosis is enhanced in interferon-gamma (IFNγ) exposed cells due to the actions of members of the guanylate binding protein (GBP) family. GBPs promote activation of caspase-4 (CASP4) by enhancing its interactions with lipopolysaccharide (LPS), a component of the outer envelope of Gram-negative bacteria. Once activated, CASP4 promotes the formation of non-canonical inflammasomes, signaling platforms that mediate pyroptosis. To establish an infection, intracellular bacterial pathogens, likeShigellaspecies, inhibit pyroptosis. The pathogenesis ofShigellais dependent on its type III secretion system, which injects ~30 effector proteins into host cells. Upon entry into host cells,Shigellaare encapsulated by GBP1, followed by GBP2, GBP3, GBP4, and in some cases, CASP4. It has been suggested that the recruitment of CASP4 to bacteria leads to its activation. Here, we demonstrate that twoShigellaeffectors, OspC3 and IpaH9.8, cooperate to inhibit CASP4-mediated pyroptosis. We show that in the absence of OspC3, an inhibitor of CASP4, IpaH9.8 inhibits pyroptosis via its known degradation of GBPs. We find that, while some LPS is present within the host cell cytosol of epithelial cells infected with wild typeShigella, in the absence of IpaH9.8, increased amounts are shed in a GBP1-dependent manner. Furthermore, that additional IpaH9.8 targets, likely GBPs, promote CASP4 activation, even in the absence of GBP1. These observations suggest that by promoting LPS release, GBP1 provides CASP4 access to LPS, thus promoting host cell death via pyroptosis.Significance StatementNon-canonical inflammasomes mediate the death of intestinal epithelial cells in response to invading Gram-negative bacterial pathogens. CASP4 is activated upon binding to LPS. Recent studies have suggested that GBP1 recruits and enables the activation of CASP4 on the surface of intracytosolic bacteria. This has led to the proposal that non-canonical inflammasomes assemble on the bacterial surface due to GBP1-mediated access of CASP4 to the membrane-embedded lipid A component of LPS. Here, we show that by targeting the degradation of GBPs,ShigellaIpaH9.8 limits the release of LPS from intracellularShigellainto the host cell cytosol in a GBP1-dependent manner. Furthermore, we find evidence to suggest that in the absence of GBP1, other members of the GBP family promote CASP4 activation.
Diversified repertoire of phage resistance inKlebsiella pneumoniaeand bidirectional steering effects impacting antibiotic susceptibility
Authors: Nang Sue C. , Lu Jing , Yu Heidi H. , Wickremasinghe Hasini , Azad Mohammad A. K. , Han Meiling , Zhao Jinxin , Rao Gauri , Bergen Phillip J. , Velkov Tony , Sherry Norelle , McCarthy David T. , Aslam Saima , Schooley Robert T. , Howden Benjamin P. , Barr Jeremy J. , Zhu Yan , Li Jian 
Published: November 2022

AbstractBacteriophage (phage) therapy is rising as a promising anti-infective option to combat antimicrobial resistance; however, its clinical utilization is severely hindered by the potential emergence of phage resistance. Fortunately, certain phage resistance mechanisms can restore bacterial antibiotic susceptibility, making the combination of phages with antibiotics a potential strategic approach. Here, we demonstrated that phage resistance can also lead to increased antibiotic resistance and provided mechanistic insights into bacterial phage defense mechanisms. We discovered a repertoire of phage resistance mechanisms inKlebsiella pneumoniae, including the disruption of phage binding site (fhuA::Tn andtonB::Tn), extension of phage latent period (mnmE::Tn andrpoN::Tn) and increased mutation frequency (mutS::Tn andmutL::Tn). Different from the prevailing view that phage resistance re-sensitizes antibiotic-resistant bacteria, we revealed a bidirectional steering effect on the bacterial antibiotic susceptibility. Specifically, it was uncovered that, whilerpoN::Tn became more susceptible to colistin,mutS::Tn andmutL::Tn caused increased resistance to rifampicin and colistin. Our findings highlight the diversified strategies utilized byK. pneumoniaeto overcome phage infection and the parallel effect on the antibiotic susceptibility. Mechanism-guided phage steering represents a rational strategy that should be incorporated into phage therapy to better inform clinical decisions.
Splicing quality control mediated by DHX15 and its G-patch activator, SUGP1
Authors: Feng Qing , Krick Keegan , Chu Jennifer , Burge Christopher B. 
Published: November 2022

ABSTRACTPre-mRNA splicing is surveilled at different stages by quality control (QC) mechanisms. The leukemia-associated DExH-box family helicasehDHX15/scPrp43, is known to disassemble spliceosomes after splicing. Here, using rapid protein depletion and analysis of nascent and mature RNA to enrich for direct effects, we identified a widespread splicing QC function for DHX15 in human cells, consistent with recentin vitrostudies. We found that suboptimal introns with weak splice sites, multiple branch points, and cryptic introns are repressed by DHX15, suggesting a general role in promoting splicing fidelity. We identified SUGP1 as a G-patch factor that activates DHX15’s splicing QC function. This interaction is dependent on both DHX15’s ATPase activity and on SUGP1’s ULM domain. Together, our results support a model in which DHX15 plays a major role in splicing QC when recruited and activated by SUGP1.
The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity
Authors: Stewart Hazel , Lu Yongxu , O’Keefe Sarah , Valpadashi Anusha , Cruz-Zaragoza Luis Daniel , Michel Hendrik A. , Nguyen Samantha K. , Carnell George W. , Lukhovitskaya Nina , Milligan Rachel , Jungreis Irwin , Lulla Valeria , Davidson Andrew D. , Matthews David A. , High Stephen , Rehling Peter , Emmott Edward , Heeney Jonathan L. , Edgar James R. , Smith Geoffrey L. , Firth Andrew E. 
Published: November 2022

SUMMARYThe SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localises to mitochondria during infection, where it inhibits innate immunity by restricting IFN-β production, but not NF-κB activation or JAK-STAT signalling downstream of type I IFN stimulation. We find that ORF3c acts after stimulation with cytoplasmic RNA helicases RIG-I or MDA5 or adaptor protein MAVS, but not after TRIF, TBK1 or phospho-IRF3 stimulation. ORF3c co-immunoprecipitates with the antiviral proteins MAVS and PGAM5 and induces MAVS cleavage by caspase-3. Together, these data provide insight into an uncharacterised mechanism of innate immune evasion by this important human pathogen.
Single-molecule analysis of receptor-β-arrestin interactions in living cells
Authors: Grimes Jak , Koszegi Zsombor , Lanoiselée Yann , Miljus Tamara , O’Brien Shannon L. , Stepniewski Tomasz M , Medel-Lacruz Brian , Baidya Mithu , Makarova Maria , Owen Dylan M. , Shukla Arun K. , Selent Jana , Hill Stephen J. , Calebiro Davide 
Published: November 2022

SUMMARYβ-arrestin plays a key role in G protein-coupled receptor (GPCR) signaling and desensitization. Despite recent structural advances, the mechanisms that govern receptor–β-arrestin interactions at the plasma membrane of living cells remain elusive. Here, we combine single-molecule microscopy with molecular dynamics simulations to dissect the complex sequence of events involved in β-arrestin interactions with both receptors and the lipid bilayer. In contrast to the currently widely accepted model, we show that β-arrestin spontaneously inserts into the lipid bilayer and transiently interacts with receptors via lateral diffusion on the plasma membrane. Moreover, we show that following receptor interaction, the plasma membrane stabilizes β-arrestin in a membrane-bound, active-like conformation, allowing it to diffuse to clathrin coated pits separately from the activating receptor. These results challenge our current understanding of β-arrestin function at the plasma membrane, revealing a new critical role for β-arrestin pre-association with the lipid bilayer in facilitating its interactions with receptors and subsequent activation.
Linking knowledge acquisition, knowledge dissemination, and manufacturing SMEs’ sustainable performance: the mediating role of knowledge application
Authors: Al Koliby Ibraheem Saleh , Mohd Suki Norazah , Abdullah Haim Hilman 
Published: November 2022

PurposeThis study aims to examine the impact of knowledge acquisition and dissemination on the sustainable performance of small- and medium-sized enterprises (SMEs). Additionally, the mediating role of knowledge application in this relationship is investigated.Design/methodology/approachData collected from 428 manufacturing SMEs in Malaysia were analyzed using the partial least squares structural equation modeling approach.FindingsThe results reveal that knowledge acquisition significantly impacts the sustainable performance of manufacturing SMEs, and knowledge application partially mediates this impact. Cutting-edge knowledge from within or outside the organization enables a deeper understanding of information regarding new products/services, a list of competing suppliers, consumer preferences and so on.Research limitations/implicationsThis study combined the knowledge-based view theory and the triple bottom line framework into a unified conceptual framework and examined the impact of knowledge acquisition and dissemination on manufacturing SMEs’ sustainable performance as well as the mediating role of knowledge application on manufacturing SMEs’ sustainable performance.Practical implicationsManufacturing SMEs should emphasize knowledge application in business operations and encourage employees to develop and enhance their knowledge acquisition and dissemination to leverage knowledge in ways that enhance business operations, produce new products and generate new knowledge assets.Originality/valueThis study is unique in that it highlights the partially mediated effects of knowledge application on the linkages between knowledge acquisition and manufacturing SMEs’ sustainable performance and the fully mediated effects of knowledge application on the association between knowledge dissemination and sustainable performance of manufacturing SMEs.
The truant distributor: retain or replace?
Authors: Kamath Renuka , Agrawal Pankaj , Ahmed Shoaib 
Published: November 2022

Learning outcomes
This case highlights the challenges faced by a young and inexperienced Area Sales Manager (ASM), early in her career. This is an often-encountered situation by fresh graduates. Through the analysis of the case, the students will be able to: ■ understand challenges a young manager faces in taking over a new, unfamiliar and underperforming territory; ■ analyze and learn to manage data and identify performance gaps in the territory, by selecting the right metrics; ■ learn the factors for evaluating the performance of current intermediaries (distributors); and ■ appreciate the importance of managing all stakeholders – internal team and building a strong relationship with the intermediaries – both distributors and retailers.

Case overview/synopsis
Kavita Kaur, the new Area Sales Manager at Broadway India Pvt. Ltd. (BIPL), had just taken over the Chhattisgarh sales territory in January 2020. Fresh out of a B-school, it was her first job, and her allotted territory was severely lagging growth at only 1%, compared to an all-India country growth at 13% in 2019, over the previous year. The territory was operated by established intermediaries (distributors) with long associations with BIPL. Based on her data analyses of distributors’ performance, Kaur started her retail visit with the highest selling distributor’s area (Sharda Agencies) to confirm her understanding of what the data had shown her. Following her retail visit and a meeting with Sharda Agencies, the situation turned for the worse. An email bordering to a threat from him took her aback. Kaur now had to make a choice to ensure growth in her new territory. Her options were between placating the current distributor or appointing a new one – should she retain or replace? Both had their own risks.

Complexity academic level
This case is intended for use at the postgraduate level in courses such as sales management, channel management and strategic marketing courses, as well as in executive management programs. The case is relevant from the context of channel management in India, where channel intermediaries can be very demanding. The case will give students a practical hands-on decision-making situation, where there are complexities of quantitative and qualitative nature. It will also help young graduates prepare for real life situations where the assigned territory is struggling in performance and a lot is expected from the new recruits.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 8: Marketing.
Achieving sustainability in South African commercial properties: the impact of innovative technologies on energy consumption
Authors: Moghayedi Alireza , Hübner Dylan , Michell Kathy 
Published: November 2022

Purpose
This study aims to examine the concept of innovative technologies and identify their impacts on the environmental sustainability of commercial properties in South Africa. This slow adoption is attributed to South Africa’s energy building regulation, SANS 204, which does not promote energy-conscious commercial property development. Furthermore, it was observed that buildings waste significant amounts of energy as electrical appliances are left on when they are not in use, which can be prevented using innovative technologies.

Design/methodology/approach
The researchers attempted to evaluate the impact of innovative technologies through an overarching constructivist mixed-method paradigm. The research was conducted using a multi-case study approach on green buildings which had innovative technologies installed. The data collection took the form of online, semi-structured interviews, where thematic analysis was used to identify emergent themes from the qualitative data, and descriptive statistics was used to evaluate the quantitative data.

Findings
It was found that implementing innovative technologies to reduce the energy consumption of commercial buildings could achieve energy savings of up to 23%. Moreover, a commercial building’s carbon footprint can be reduced to 152CO2/m2 and further decreased to 142CO2/m2 through the adoption of a Photovoltaics plant. The study further found that innovative technologies improved employee productivity and promoted green learning and practices.

Originality/value
This research demonstrated the positive impact innovative technologies have on energy reduction and the sustainability of commercial properties. Hence, facility managers should engage innovative technologies when planning a commercial development or refurbishment.
The impact of servitization on trade credit in manufacturing firms: a signaling theory perspective
Authors: Wang Weijiao , Chen Shanshan , Shao Jinan , Chu Junfei , Yuan Zhe 
Published: November 2022

PurposeThe aim of this study is to empirically test the link between servitization and trade credit in manufacturing firms as well as the boundary conditions of this link.Design/methodology/approachUsing a unique dataset of 4,974 observations covering 838 manufacturing firms publicly listed in the United States during 1990–2020, this study examines the impact of servitization on trade credit and the moderating impacts of financial slack and service relatedness based on fixed-effect regression models.FindingsThe authors find that servitization shows a U-shaped relationship with trade credit. Besides, financial slack negatively moderates this U-shaped relationship whereas service relatedness has no significant impact on this relationship.Originality/valueThis paper is the first to empirically verify the influence of servitization on trade credit in manufacturing firms based on longitudinal secondary data and signaling theory. The research findings can provide several important theoretical and managerial implications for scholars and practitioners in operations management.
Analysis of the financial sustainability of the cooperative savings and credit sector in Peru
Authors: Flores-Chia James , Mougenot Benoit 
Published: November 2022

PurposeThis research analyzes the determinants of the financial sustainability of the cooperative savings and credit sector in Peru.Design/methodology/approachThe econometric analysis uses a balanced data panel with a sample of 34 savings and credit cooperatives in Peru for the period 2010–2017. The estimates were considered using the static fixed-effects model to assess the financial sustainability.FindingsThe results show that the interest rate differential, the number of years of activity, the size of assets and the return on assets are explanatory variables of the financial sustainability of savings and credit cooperatives in Peru.Research limitations/implicationsThis research promotes reflection and discussion for the design of policies that improve the level of competition for the Peruvian savings and credit cooperative model, based on the level of financial sustainability.Originality/valueThis study is one of the first to identify the determinants of the financial sustainability of the savings and credit cooperative sector in Peru.Peer reviewThe peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-01-2022-0064
Explaining variation in the implementation of observational processes by school leaders: evidence from a Tennessee-based researcher–practitioner partnership
Authors: Hunter Seth B. 
Published: November 2022

PurposeRecent teacher evaluation reforms across the globe can improve student outcomes, though doing so depends on implementation by school leaders. This study aims to describe how teacher reports about classroom observation processes (TROPs) vary across within-teacher observations, teachers and schools and depend on contextual, teacher and school characteristics.Design/methodology/approachA researcher–practitioner partnership collected TROPs using surveys administered multiple times during one semester and linked results to Tennessee administrative data. Random effects quantify TROP variation within examined clusters and estimate relationships between TROPs and the examined characteristics.FindingsAlthough observation processes are well implemented on average, TROPs vary considerably across teachers and observations within teachers over a short period. TROPs also depend on several examined characteristics, but not necessarily in ways predisposed toward teacher development.Originality/valueThe study extends the understanding of the degree and extent to which teacher evaluation implementation by school leaders varies. Leadership preparation programs and in-service support providers might use the evidence herein to improve the extent to which evaluation-related observation processes are implemented consistently and in ways supporting teacher development.