bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel green fluorescent polyamines to analyze ATP13A2 and ATP13A3 activity in the mammalian polyamine transport system
Authors: Houdou Marine , Jacobs Nathalie , Coene Jonathan , Azfar Mujahid , Vanhoutte Roeland , Van den Haute Chris , Eggermont Jan , Daniëls Veronique , Verhelst Steven H. L. , Vangheluwe Peter 
Published: December 2022

AbstractCells acquire the polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM)viathe complementary action of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian polyamine uptake. Our biochemical evidence shows that fluorescently labeled polyamines are genuine substrates of ATP13A2. They can be used to measure polyamine uptake in ATP13A2 and ATP13A3-dependent cell models resembling radiolabeled polyamine uptake. We further report that ATP13A3 enables faster and stronger cellular polyamine uptake than ATP13A2. We also compared the uptake of new green-fluorescent PUT, SPD and SPM analogs using different coupling strategies (amide, triazole or isothiocyanate) and fluorophores (symmetrical BODIPY, BODIPY-FL and FITC). ATP13A2 promotes the uptake of various SPD and SPM analogs, whereas ATP13A3 mainly stimulates the uptake of PUT and SPD conjugates. However, the polyamine linker and coupling position on the fluorophore impacts the transport capacity, whereas replacing the fluorophore affects polyamine selectivity. The highest uptake in ATP13A2 or ATP13A3 cells is observed with BODIPY-FL-amide conjugated to SPD, whereas BODIPY-PUT analogs are specifically taken upviaATP13A3. We found that P5B-type ATPase isoforms transport fluorescently labeled polyamine analogs with a distinct structure-activity relationship (SAR) suggesting that isoform-specific polyamine probes can be designed.
Fern cell walls and the evolution of arabinogalactan-proteins in streptophytes
Authors: Mueller Kim-Kristine , Pfeifer Lukas , Schuldt Lina , Szövényi Péter , de Vries Sophie , de Vries Jan , Johnson Kim L. , Classen Birgit 
Published: December 2022

SUMMARYSignificant changes have occurred in plant cell wall composition during evolution and diversification of tracheophytes. As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). Here, we characterize the AGPs from the leptosporangiate fern generaAzolla,SalviniaandCeratopteris. The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. Yet, unlike AGPs of angiosperms, those of ferns contained the unusual sugar 3-O-methylrhamnose. Besides terminal furanosidic Ara (Araf), the main linkage type of Arafin the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Arafis often dominating. Antibodies directed against carbohydrate epitopes of AGPs supported the structural differences between AGPs of ferns and seed plants. Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. Our data reveal important differences across AGP diversity which functional significance is unknown. This diversity sheds light on the evolution of the hallmark feature of tracheophytes: their elaborate cell walls.SIGNIFICANCE STATEMENTFerns are the sister lineage of seed plants and key to understanding plant evolution. To understand ferns’ unique cell walls, we analysed arabinogalactan-proteins from the fern generaAzolla,SalviniaandCeratopteris. Comparison of AGP structures throughout the streptophyte lineage reveals special features in relation to systematic positions and proposes a trend to more hydrophilic AGPs in course of evolution. Through comparative genomic analyses, we pinpoint the potential genetic players for this diversity in cell walls.
Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection
Authors: Guenthoer Jamie , Lilly Michelle , Starr Tyler N. , Dadonaite Bernadeta , Lovendahl Klaus N. , Croft Jacob T. , Stoddard Caitlin I. , Chohan Vrasha , Ding Shilei , Ruiz Felicitas , Kopp Mackenzie S. , Finzi Andrés , Bloom Jesse D. , Chu Helen Y. , Lee Kelly K. , Overbaugh Julie 
Published: December 2022

AbstractThe antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs through BA.4/BA.5 in both pseudovirus-based and authentic virus assays. Three mAbs also retain potency to recently circulating VOCs XBB.1.5 and BQ.1.1 and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are novel in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.Significance StatementSARS-CoV-2 infections can result in diverse clinical outcomes, including severe disease. Monoclonal antibodies (mAbs) have been used therapeutically to treat infection, but the emergence of variants has compromised their efficacy. Thus, identifying mAbs that are more durable in the face of SARS-CoV-2 evolution is a pressing need. Here, we describe four new mAbs isolated from a Delta-breakthrough infection, that can potently neutralize diverse variants, including multiple Omicron variants. In addition, one mAb shows broader activity against coronaviruses. The breadth of these mAbs is due to their focus on highly conserved regions of the viral protein antigen, including regions that are required for the virus to enter the cell. These properties make them promising candidates for therapeutic use.
Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant
Authors: Wang Qiang , Martínez-Bonet Marta , Kim Taehyeung , Sparks Jeffrey A. , Ishigaki Kazuyoshi , Chen Xiaoting , Sudman Marc , Aguiar Vitor , Hernandez Marcos Chiñas , Wactor Alexandra , Wauford Brian , Marion Miranda C. , Gutierrez-Arcelus Maria , Bowes John , Eyre Stephen , Nordal Ellen , Prahalad Sampath , Rygg Marite , Videm Vibeke , Raychaudhuri Soumya , Weirauch Matthew T. , Langefeld Carl D. , Thompson Susan D. , Nigrovic Peter A. 
Published: December 2022

ABSTRACTTRAF1/C5 was among the first loci shown to confer risk for inflammatory arthritis in the absence of an associated coding variant, but its genetic mechanism remains undefined. Using ImmunoChip data from 3,939 juvenile idiopathic arthritis (JIA) patients and 14,412 controls, we identified 132 plausible common non-coding variants, reduced serially by SNP-seq, electrophoretic mobility shift, and luciferase studies to the single variant rs7034653 in the third intron ofTRAF1. Genetically manipulated experimental cells and primary monocytes from genotyped donors establish that the risk G allele reduces binding of Fos-Related Antigen 2 (FRA2), resulting in reduced TRAF1 expression and enhanced TNF production. Conditioning on this variant eliminates attributable risk for rheumatoid arthritis, implicating a mechanism shared across the arthritis spectrum. These findings reveal that rs7034653, FRA2, and TRAF1 mediate a pathway through which a non-coding causal variant drives risk of inflammatory arthritis in children and adults.
Accuracy-speed-stability trade-offs in a targeted stepping task are similar in young and older adults
Authors: Muijres Wouter , Arnalsteen Sylvie , Daenens Cas , Afschrift Maarten , De Groote Friedl 
Published: December 2022

AbstractBackgroundStepping accuracy, speed, and stability are lower in older compared to young adults. Lower stepping performance in older adults may be due to larger accuracy-speed-stability trade-offs because of reduced ability to simultaneously fulfill these task-level goals. Our goal was to evaluate whether trade-offs are larger in older compared to young adults in a targeted stepping task. Since sensorimotor function declines with age, our secondary goal was to evaluate whether poorer sensorimotor function was associated with larger trade-offs.Methods25 young (median 22 years old) and 25 older (median 70 years old) adults stepped into projected targets in conditions with various levels of accuracy, speed, and stability requirements. We determined trade-offs as the change in performance, i.e. foot placement error, step duration, and mediolateral center of pressure path length, between each of these conditions and a control condition. To assess age-related differences in the magnitude of trade-offs, we compared the change in performance between age groups. Associations between trade-offs and measures of sensorimotor function were tested using correlations.ResultsWe found an accuracy-speed and an accuracy-stability trade-off in both young and older adults, but trade-offs were not different between young and older adults. Inter-subject differences in sensorimotor function could not explain inter-subject differences in trade-offs.ConclusionAge-related differences in the ability to combine task-level goals do not explain why older adults stepped less accurate and less stable than young adults. However, lower stability combined with an age-independent accuracy-stability trade-off could explain lower accuracy in older adults.
Structure of Phosphorylated-like ClpXP Adaptor RssB Reveals an Interface Switch for Activation
Authors: Brugger Christiane , Schwartz Jacob , Filipovski Martin , Deaconescu Alexandra M. 
Published: December 2022

SUMMARYIn γ-proteobacteria such asEscherichia coli, the general stress response is mediated by σs, the stationary phase dissociable promoter specificity subunit of RNA polymerase. σsis degraded by ClpXP during active growth in a process dependent on the RssB adaptor, which acts catalytically and is thought to be stimulated by phosphorylation of a conserved aspartate in its N-terminal receiver domain. Here we present the crystal structure of full-length RssB bound to a beryllofluoride phosphomimic. Compared to the inhibited IraD anti-adaptor-bound RssB structure, our study reveals movements and coil-to-helix transitions in the C-terminal region of the RssB receiver domain and in the inter-domain segmented helical linker, accompanied by packing of the C-terminal effector domain onto the α4-β5-α5 (4-5-5) “signaling” face of the RssB receiver domain. This face is often the locus of protein-protein interactions in unphosphorylated receiver domains, but its masking is unusual in their phosphorylated forms. Our structure emphasizes the remarkable plasticity that underpins regulatory strategies within the large family of response regulators.
Molecular profiling in HNSCC patients targets potential responsiveness to ICIs
Authors: Sacconi Andrea , Muti Paola , Pulito Claudio , Pellini Raul , Strano Sabrina , Bossi Paolo , Blandino Giovanni 
Published: December 2022

AbstractImmunotherapy is emerging as a valid therapeutic strategy for various cancers although only a subset of patients responding to the therapy. The response to immunotherapy remains low for many cancer types because of poor ability to appropriately classify responding patients.We analyzed TCGA cohort of HNSCC patients in relation to a 26 immune gene set and cell types to define signaling pathways associated with resistance to immune checkpoint blockade. Results were validated on a cohort of 102 HNSCC patients under treatment with PD-L1 inhibitors and byin vitroexperiments.Using bioinformatic approach, we observed a significant association between the gene set and TP53 gene status and other predictors of ICIs’ response in HNSCC patients. The presence of both TP53 mutation and co-mutations was associated with significantly higher levels of the immune gene expression than in lesions with only the TP53 mutated. We also observed that higher level of a MYC signature was associated with lower level of the immune gene expression.In vitroand cohort validation corroborated the evidence.SIGNIFICANCEImmune gene signature sets represent biomarkers to be implemented for the better classification of those HNSCC patients responsive to immunotherapy. A particular advantage of these biomarkers is the ability to characterize HNSCC patients using tumor tissues easily applicable in clinical setting.
The moderating impact of auditor industry specialisation on the relationship between fair value disclosure and audit fees: empirical evidence from Jordan
Authors: Alharasis Esraa Esam , Prokofieva Maria , Clark Colin 
Published: December 2022

PurposeThis paper investigates the application of the product differentiation and shared efficiency approaches to understand the impact of the auditor industry specialisation (IS) on audit fees in relation to Fair Value Disclosures (FVD).Design/methodology/approachThe study uses 1,470 firm-year observations for the period 2005–2018 and is focused on Jordanian financial firms. Two competing theoretical approaches of IS proxied by audit fee-based measures were employed: firstly, the product differentiation approach measured using Market Share-based (MS) measure and secondly, the shared efficiency approach measured using Portfolio Share-based (PS) measure. The paper employs the Ordinary Least Squares regression to test the association between the proportion of fair-valued assets (using fair value hierarchy inputs) and audit fees.FindingsThe results suggest that the association between the proportion of fair-valued assets and audit fees is strengthened (weakened) when the client hires specialist auditors identified by MS (PS). This association varied across the fair value inputs. Level 1 assets were found to be only moderated by both scenarios positively (negatively) for MS (PS) experts. The results are robust after controlling the endogeneity of auditor self-selection.Practical implicationsThe results provide valuable insights for policymakers into challenges of auditing FVD. These insights present a valuable input for the development of FVD policies and practices as well as providing guidance for updating auditor prices. Additionally, the results provide a foundation for policymakers and regulators to introduce and update fair value auditing practices. The current findings are generalisable to other countries, including the Middle East and North Africa, and are particularly beneficial for those countries which have adopted the fair value model.Originality/valueThis study contributes to the theory by demonstrating the impact of the auditor industry expertise on post-implementation costs of FVD. The novelty of the study lies in introducing principle-based standards requirements of FVD to test the relationship. This approach is based on the IFRS disclosure requirements using data from the Jordanian financial sector to examine this relationship.
Improving automated pallet handling procedures at a Saudi milk factory through overall equipment effectiveness
Authors: Alnounou Reham Tarek , Asiri Rawan Ahmed , Alhindi Sara Ayman , Shams Layan Marwan , Ali Sadia Samar , Özceylan Eren 
Published: December 2022

PurposeSaudi Arabia's 2030 vision targets an increase of 34% in non-oil revenue participation in the GDP, thus the need for automation and digital transformation. The Company ER is a market leader producing high-quality dairy products in the Kingdom and is a pioneer in the production industry. The company has recently increased the capacity of its milk factory to meet its vision. An investment was made to automate the pallet handling procedures at the milk factory to provide increased production for daily consumption. The new automation transition in Company ER's milk factory provides a unique opportunity to utilize lean management tools to improve the current automated processes before commercialization.Design/methodology/approachOEE (overall equipment effectiveness) will monitor losses for different operational losses in the new automated system and indicate system improvements, with 85% as the target. Based on DMADV (design, measure, analyze, design and validate) methodology, this study analyzes the entire automated pallet handling system. It uses lean tools to identify areas for improvement, identify waste elements and propose solutions to achieve Company ER's OEE targets.FindingsIn this paper, the outcomes will be presented as documented solutions that address the losses encountered in the production system, showing a 12.8% increase in the system's OEE.Research limitations/implicationsOwing the time and resource constraint, this study only involved automated pallet handling procedures in a milk production facility. Hence, the generalization of the result is slightly limited. More studies in several different processes and sectors are required.Practical implicationsThis study provided a valuable tool for researchers for gaining deeper understanding regarding the lean manufacturing and its implementation. For practitioners, it is useful to evaluate the degree of lean manufacturing tools in their material handling systems.Originality/valueThis study is the first attempt to develop lean manufacturing constructs for evaluating the automated pallet handling procedures in a milk production facility.
Nonlinear dynamic analysis of wrinkled membrane structure
Authors: Liu Xiang , Cai G.P. 
Published: December 2022

PurposeThis paper studies the nonlinear dynamics of membrane structure considering wrinkling effect. The coupling between wrinkles and vibration is investigated elaborately, and new insight on the dynamics of wrinkled membrane is unveiled.Design/methodology/approachBased on the stability theory of plates and shells, the wrinkling model of the membrane structure is established. Considering the effects of wrinkling and nonlinearity, the dynamic response is calculated with NewMark method.FindingsWrinkling will impact the dynamics of the membrane structure significantly for asymmetrical tension loading cases, dynamic response of the wrinkled membrane structure can be classified into three categories: when the vibration is small, the dynamics of the wrinkled membrane structure will behave linearly, and the wrinkles will only affect the dynamic properties as initial conditions; when the vibration is relatively large, the wrinkles will interact with the vibration during the dynamic process, and the dynamics of the structure shows very complex features; when the vibration is large enough, the dynamics will be dominated by the geometric nonlinearity of large-amplitude vibration.Originality/valueIn the previous works on dynamics of wrinkled membrane structure, only the vibration modes have been studied, which means all those investigations are confined with linear vibration; little research has been conducted on the nonlinear dynamics of wrinkled membrane structure. In view of this, this paper presents an investigation of dynamic properties of membrane structure considering the wrinkling and geometric nonlinear effects. This research work presents some novel discoveries on the nonlinear dynamics of wrinkled membrane.
Past for Future – museums as a digitalized “interaction platform” for value co-creation in tourism destinations
Authors: Massari Francesco Saverio , Del Vecchio Pasquale , Degl'innocenti Eva 
Published: December 2022

PurposeThis paper aims to explore how digital technologies can transform the museum into an “interaction platform” able to play a key role in the value co-creation processes of the tourism destination.Design/methodology/approachThe paper applies the “co-creation through interactions” perspective by Ramaswamy and Ozcan. Empirically, the paper is based on the methodology of single case study identified in MArTA, the well-known National Archeological Museum of Taranto (South Italy). Data collection has been implemented through interviews with key informants and secondary data related to online interviews, press release and reports.FindingsFindings provide empirical evidence about the contribution that a digitalization strategy can create a “museum as a platform” in which the interactions between the museum, its stakeholders and other co-creation elements (interfaces, artifacts and processes) bring benefits in terms of tourism experiences and sustainable development of the destination.Practical implicationsThis research highlights the cultural changes and the actions that museum management has to implement to properly benefit from digitalization and to transform the museum into a reference point for reflection and innovation.Originality/valueElements of originality can be found in (1) the exploration of the wide spectrum of benefits and innovations that digital technologies can offer to the museum-mediated interactions and (2) the contribution to the understanding of the museum as a digitalized “interaction platform” capable of supporting the processes of co-creation of value in the complex network of actors and objects of a tourism destination.
The pandemic did not interrupt LA’s violence interrupters
Authors: Ren Jiaoying , Santoso Karina , Hyde David , Bertozzi Andrea L. , Brantingham P. Jeffrey 
Published: December 2022

PurposeThe impact of the COVID-19 pandemic on crime has been highly variable. One possible source of variation runs indirectly through the impact that the pandemic had on groups tasked with preventing and responding to crime. Here, this paper aims to examine the impact of the pandemic on the activities undertaken by front-line workers in the City of Los Angeles Mayor’s Office of Gang Reduction and Youth Development (GRYD).Design/methodology/approachThe authors use both autoregressive integrated moving average modeling and a regression-based event study design to identify changes in GRYD Community Intervention Worker proactive peacemaking and violence interruption activities induced by the onset of the City of Los Angeles “safter-at-home” lockdown.FindingsAnalyses show that the proactive peacemaking and violence interruption activities either remained stable or increased with the onset of the lockdown.Originality/valueWhile the City of Los Angeles exempted GRYD’s Community Intervention Workers from lockdown restrictions, there was no guarantee that proactive peacemaking and violence interruption activities would continue unchanged. The authors conclude that these vital functions were indeed resilient in the face of major disruptions to daily life presented by the pandemic. However, the causal connection between stability in Community Intervention Worker activities and gang-related crime remains to be evaluated.