bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-canonical DNA in human and other ape telomere-to-telomere genomes
Authors: Smeds Linnéa , Kamali Kaivan , Kejnovská Iva , Kejnovský Eduard , Chiaromonte Francesca , Makova Kateryna D. 
Published: September 2024

AbstractNon-canonical (non-B) DNA structures—e.g., bent DNA, hairpins, G-quadruplexes, Z-DNA, etc.—which form at certain sequence motifs (e.g., A-phased repeats, inverted repeats, etc.), have emerged as important regulators of cellular processes and drivers of genome evolution. Yet, they have been understudied due to their repetitive nature and potentially inaccurate sequences generated with short-read technologies. Here we comprehensively characterize such motifs in the long-read telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. Non-B DNA motifs are enriched at the genomic regions added to T2T assemblies, and occupy 9-15%, 9-11%, and 12-38% of autosomes, and chromosomes X and Y, respectively. Functional regions (e.g., promoters and enhancers) and repetitive sequences are enriched in non-B DNA motifs. Non-B DNA motifs concentrate at short arms of acrocentric chromosomes in a pattern reflecting their satellite repeat content and might contribute to satellite dynamics in these regions. Most centromeres and/or their flanking regions are enriched in at least one non-B DNA motif type, consistent with a potential role of non-B structures in determining centromeres. Our results highlight the uneven distribution of predicted non-B DNA structures across ape genomes and suggest their novel functions in previously inaccessible genomic regions.Graphical Abstract
Elucidating the Selection Mechanisms in Context-Dependent Computation through Low-Rank Neural Network Modeling
Authors: Zhang Yiteng , Feng Jianfeng , Min Bin 
Published: September 2024

AbstractHumans and animals exhibit a remarkable ability to selectively filter out irrelevant information based on context. However, the neural mechanisms underlying this context-dependent selection process remain elusive. Recently, the issue of discriminating between two prevalent selection mechanisms— input modulation versus selection vector modulation—with neural activity data has been highlighted as one of the major challenges in the study of individual variability underlying context-dependent decision-making (CDM). Here, we investigated these selection mechanisms through low-rank neural network modeling of the CDM task. We first showed that only input modulation was allowed in rank-one neural networks and additional dimensions of network connectivity were required to endow neural networks with selection vector modulation. Through rigorous information flow analysis, we gained a mechanistic understanding of why additional dimensions are required for selection vector modulation and how additional dimensions specifically contribute to selection vector modulation. This new understanding then led to the identification of novel neural dynamical signatures for selection vector modulation at both single neuron and population levels readily testable in experiments. Together, our results provide a rigorous theoretical framework linking network connectivity, neural dynamics and selection mechanisms, paving the way towards elucidating the circuit mechanisms when studying individual variability in context-dependent computation.
β-barrel proteins dictate the effect of core oligosaccharide composition on outer membrane mechanics
Authors: Fitzmaurice Dylan , Amador Anthony , Starr Tahj , Hocky Glen M. , Rojas Enrique R. 
Published: September 2024

AbstractThe outer membrane is the defining structure of Gram-negative bacteria. We previously demonstrated that it is critical for the mechanical integrity of the cell envelope and therefore to the robustness of the bacterial cell as a whole. Here, to determine the key molecules and moieties within the outer membrane that underlie its contribution to cell envelope mechanics, we measured cell-envelope stiffness across several sets of mutants with altered outer-membrane sugar content, protein content, and electric charge. To decouple outer membrane stiffness from total cell envelope stiffness, we developed a novel microfluidics-based “osmotic force extension” assay. In tandem, we developed a simple method to increase throughput of microfluidics experiments by performing them on color-coded pools of mutants. UsingEscherichia colias a model Gram-negative bacterium, we found that truncating the core oligosaccharide, deleting the β-barrel protein OmpA, or deleting lipoprotein outer membrane-cell wall linkers all had the same modest, convergent effect on total cell-envelope stiffness but had large, varying effects on the ability of the cell wall to transfer tension to the outer membrane during large hyperosmotic shocks. Surprisingly, altering lipid A charge had little effect on the mechanical properties of the envelope. Importantly, the presence or absence of OmpA determined whether truncating the core oligosaccharide decreased or increased envelope stiffness (respectively), revealing sign epistasis between these components. Based on these data we propose a specific structural model in which the chemical interactions between lipopolysaccharides, β-barrel proteins, and phospholipids coordinately determine cell envelope stiffness, and the ability of the outer membrane to functionally share mechanical loads with the cell wall.Statement of SignificanceThe outer membrane is the defining cellular structure of Gram-negative bacteria, a group that contains many important pathogens likeEscherichia coli,Vibrio cholerae, andPseudomonas aeruginosa. One role of the outer membrane is to block the uptake of small molecules like antibiotics. However, it is becoming increasingly clear that it also functions as a structural exoskeleton that is critical for the cell’s ability to cope with internal and external mechanical forces. Here, we carefully dissect the molecular basis for the load-bearing capacity of the outer membrane by screening a set of mutants with a new cell biophysics assay.
ApoE4 disrupts intracellular trafficking and iron homeostasis in an improved iPSC-based model of human brain endothelial cells
Authors: Bell Luisa , Stokar-Regenscheit Nadine , Simonneau Claire , Augustin Angélique , Höllbacher Barbara , D’Abate Lia , Ficek-Pascual Joanna , Schneider Kim , Von Tell Desiree , Zanini Chiara , Zundel Christelle , Golling Sabrina , Becker Christine , Odermatt Alex , Foo Lynette , Pigoni Martina , Villaseñor Roberto 
Published: September 2024

SummaryTransferrin receptor in brain endothelial cells can deliver therapeutic antibodies to the brain via transcytosis across the blood-brain barrier. Whether receptor transport remains intact in Alzheimer’s disease is still a major open question. Here, we investigated whether apolipoprotein E4 (ApoE4), the major genetic risk factor for Alzheimer’s disease, altered intracellular transport in human brain endothelial cells. To achieve this, we first developed an optimized protocol for induced pluripotent stem cells based on a definedchemical cocktail andextracellular-matrix support to differentiatebrainendothelialcells (iCE-BECs). Multi-omic profiling and functional transport assays showed that iCE-BECs have a brain endothelial gene signature and recapitulate receptor-mediated transcytosis of a clinically validated BrainshuttleTMantibody against transferrin receptor. Engineered iCE-BECs homozygous for ApoE4 had altered spatiotemporal organization of early endosomes, increased transferrin receptor expression and reduced cytoplasmic iron. Our data revealed that ApoE4 can impact intracellular transport and iron homeostasis at the BBB in a cell-autonomous manner. This finding could be relevant for the brain delivery of therapeutic antibodies for Alzheimer’s disease.
LL-37 modulates IL-17A/F-mediated airway inflammation by selectively suppressing Lipocalin-2
Authors: Altieri Anthony , Lloyd Dylan , Ramotar Padmanie , van der Does Anne M , Hemshekhar Mahadevappa , Mookherjee Neeloffer 
Published: September 2024

ABSTRACTBackgroundLevels of the human cationic host defence peptide (CHDP) LL-37 is enhanced in the lungs during neutrophilic airway inflammation. LL-37 drives Th17 differentiation, and Th17 cells produce IL-17A and IL-17F which forms the biologically active heterodimer IL-17A/F. While IL-17 is a critical mediator of neutrophilic airway inflammation, LL-37 exhibits contradictory functions; LL-37 can both promote and mitigate neutrophil recruitment depending on the inflammatory milieu. The impact of LL-37 on IL-17-induced responses in the context of airway inflammation remains largely unknown. Therefore, we examined signaling intermediates and downstream responses mediated by the interplay of IL-17A/F and LL-37, in human bronchial epithelial cells (HBEC). As LL-37 can get citrullinated during airway inflammation, we also examined LL-37-mediated downstream response compared to that with citrullinated LL-37 (citLL- 37), in HBEC.ResultsUsing an aptamer-based proteomics approach, we identified proteins that are altered in response to IL-17A/F in HBEC. Proteins enhanced in response to IL-17A/F were primarily neutrophil chemoattractants, including chemokines and proteins associated with neutrophil migration such as lipocalin-2 (LCN-2) and Elafin. We showed that selective depletion of LCN-2 mitigated neutrophil migration, thus functionally demonstrating LCN-2 as a critical neutrophil chemoattractant. We further demonstrated that LL-37 and citLL-37 selectively suppresses IL- 17A/F-induced LCN-2 production, in bronchial epithelial cells. Mechanistic studies revealed that LL-37 and citLL-37 suppressed IL-17A/F-mediated C/EBPβ, a transcription factor required for LCN-2 production. In contrast, LL-37 and citLL-37 enhanced the ribonuclease Regnase-1, which is a negative regulator of IL-17 and LCN-2. In an animal model of neutrophilic airway inflammation with elevated IL-17A/F in the lungs, we demonstrated that CRAMP (mouse ortholog of LL-37) negatively correlates with LCN-2.ConclusionsOverall, our findings showed that LL-37 and citLL-37 can selectively suppress the abundance of IL-17A/F-mediated LCN-2, a protein that is critical for neutrophil migration, in bronchial epithelial cells. These results suggest that LL-37, and its modified citrullinated form, has the potential to negatively regulate IL-17-mediated neutrophil migration to control airway inflammation. To our knowledge, this is the first study to report that the immunomodulatory function of LL-37 engages an RNA binding protein, Regnase-1, indicating post-transcriptional regulation of airway inflammation by the peptide.
Inference in wolves and dogs: The “cups task”, revisited
Authors: Rivas-Blanco Dániel , Krause Sophia D. , Marshall-Pescini Sarah , Range Friederike 
Published: September 2024

AbstractInferential reasoning —the process of arriving at a conclusion from a series of premises— has been studied in a multitude of animal species through the use of the “cups task” paradigm. In one of the versions of this set-up, two opaque cups —one baited, one empty— are shaken in front of the animal. As only the baited cup makes a noise when shaken, the animals can locate the reward by inferring that only a baited cup would make noise, that an empty cup would make no noise, or both. In a previous iteration of this paradigm in wolves (Canis lupus) and dogs (Canis familiaris), wolves seemed to outperform dogs. However, due to the lack of control conditions, it was not possible to assess each species’ inference capabilities, nor how they related to each other. The current study adds several conditions in which the baited cup, the empty cup, or no cups are shaken, in order to tackle this issue. Our results seem to indicate that wolves and dogs made their choices not based on inference but on the saliency and order of the stimuli presented, something that seems in line with the previous study. We discuss the potential causes behind the animals’ performance, as well as proposing alternative paradigms that may be more apt to measure inference abilities in wolves and dogs.
USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination
Authors: Bolhuis Derek L. , Fleifel Dalia , Bonacci Thomas , Wang Xianxi , Mouery Brandon L. , Cook Jeanette Gowen , Brown Nicholas G. , Emanuele Michael J. 
Published: September 2024

ABSTRACTThe CMG helicase (CDC45-MCM2-7-GINS) unwinds DNA as a component of eukaryotic replisomes. Replisome (dis)assembly is tightly coordinated with cell cycle progression to ensure genome stability. However, factors that prevent premature CMG unloading and replisome disassembly are poorly described. Since disassembly is catalyzed by ubiquitination, deubiquitinases (DUBs) represent attractive candidates for safeguarding against untimely and deleterious CMG unloading. We combined a targeted loss-of-function screen with quantitative, single-cell analysis to identify human USP37 as a key DUB preventing replisome disassembly. We demonstrate that USP37 maintains active replisomes on S-phase chromatin and promotes normal cell cycle progression. Proteomics and enzyme assays revealed USP37 interacts with the CMG complex to deubiquitinate MCM7, thus antagonizing replisome disassembly. Significantly, USP37 protects normal epithelial cells from oncoprotein-induced replication stress. Our findings reveal USP37 to be critical to the maintenance of replisomes in S-phase and suggest USP37-targeting as a potential strategy for treating malignancies with defective DNA replication control.
Investigating generalized minimal supergravity in the MSSM through the long-lived bino NLSP at the HL-LHC
Authors: Zhang Wenxing , Ahmed Waqas , Khan Imtiaz , Li Tianjun , Raza Shabbar 
Published: September 2024

The axino, the supersymmetric partner of the axion, is a well-motivated warm/hot dark/cold matter candidate and provides a natural solution to the relic density problem for the binolike neutralino if it is the lightest supersymmetric particle (LSP). With the generalized minimal supergravity, we study such kind of the viable parameter space where the binolike neutralino is the next-to-LSP (NLSP) and the axino is the LSP. In addition, we consider a scenario where the bino is a long-lived NLSP with the lifetime varying from 10−6 to 10−4  s and then propose a new signal searching scheme involving one displaced photon together with the large missing transverse momentum at the HL-LHC. The binolike lightest neutralino lies under or around 100 GeV and is produced as a decay product of the right-handed sleptons. The relevant axion coupling fa can be probed up to O(109)  GeV at 2σ level for the right-handed slepton mass under 800 GeV.

Published by the American Physical Society
2024
To lead or not to lead? A cultural examination of leadership in independent hotels
Authors: Nazarian Alireza , Zaeri Ehsan , Foroudi Pantea , Afrouzi Amirreza , Atkinson Peter 
Published: September 2024

PurposeThis study explores the impact of ethical and authentic leadership on employees' workplace perceptions, focusing on organisational citizenship behaviour (OCB), trust in leader, commitment, employee voice and empowerment in independent hotels across two contrasting Global Leadership and Organizational Behaviour Effectiveness (GLOBE) clusters: Germanic and Middle-Eastern clusters. It examines how national culture influences these relationships in the hospitality industry.Design/methodology/approachData were collected from 1,678 employees in independent hotels in the Germanic European cluster (Germany and the Netherlands) and the Middle-Eastern cluster (Qatar and Turkey) using selective and snowball sampling techniques. Hypotheses were tested using two-stage structural equation modelling.FindingsEthical leadership significantly affects employee voice in Germany and the Netherlands but not in Qatar and Turkey. Authentic leadership positively influences employee voice in Qatar, Turkey and Germany but does not significantly impact trust in leader in any of the four countries. The study underscores the role of cultural dimensions, particularly power distance, in shaping these relationships.Originality/valueThis research contributes to the literature by investigating the effects of ethical and authentic leadership on key organisational variables in culturally diverse contexts within the hospitality industry. The findings highlight the necessity of considering national culture in leadership practices and suggest practical implications for independent hotels to adapt their leadership approaches to enhance employee outcomes. Future research should explore cultural dimensions as moderators in organisational relationships.
Young adults’ perceptions of personal loan commercials
Authors: Fan Fei , Chan Kara 
Published: September 2024

Purpose
Personal debt is a common problem among Hong Kong people. Personal loan marketers promote their products and services aggressively, especially to young consumers. The purpose of this paper is to examine how young consumers respond to personal loan advertisements.

Design/methodology/approach
Face-to-face interviews were conducted with 38 interviewees in the age group of 18-25 years. They were asked to report their perceptions of three selected personal loan TV commercials and their attitudes toward personal loan advertisements in general.

Findings
Four themes were identified from the data analysis: a personal loan is a modern way of solving a debt problem; personal loan advertisements encourage materialism and overspending; personal loan advertisements are misleading; and personal loan advertisements do not affect me. The overall perception of these commercials is that borrowing money is easy and quick. Some report that they would try the product if they need to borrow money in the future.

Research limitations/implications
Given the small sample size, the findings cannot be generalized to the population. Future studies can use survey methodology to compare perceptions of personal loan advertisements by demographics.

Practical implications
Despite their effectiveness in communicating product features and benefits, personal loan advertisers suffer from negative brand image among young adults. The study has implications for socially responsible marketing for lenders.

Social implications
Credit counselors, policy makers, universities and employers should look into the need for raising the financial literacy of young adults.

Originality/value
To the best of the authors’ knowledge, this is the first study on consumers’ response to personal loan advertisements among young adults.
The New Keynesian Phillips Curve and r* ${r}^{* }$
Authors: Abbas Syed Kanwar 
Published: September 2024

AbstractIn this article, I argue that shifts in the natural rate of interest provide important insights for the New Keynesian Phillips Curve (NKPC). The deviation of the real interest rate from the natural interest rate (interest rate gap) captures the monetary policy stance, which is important for the dynamics of inflation and the output gap in the wake of persistent and permanent variation in the natural rate of interest. I present the evolution of the estimates of the Taylor‐rule consistent‐ natural interest rate, and thus the associated path of the expectations of future inflation via the Fisherian relationship. The path of these two variables has implications for estimation of the NKPC.
Insights into decision‐maker's perceptions of good versus bad decisions in emergency services—A modified Delphi study
Authors: Penney Greg , Thompson Matthew B. , Codreanu Tudor , Launder David 
Published: September 2024

AbstractDecision‐making in emergency situations, such as those faced by fire, police, and health service personnel, presents unique challenges due to the high‐stakes and time‐pressured environment. Here we aim to better understand what emergency responders regard as constituting ‘good’ and ‘bad’ decisions in emergency situations. We administered a modified Delphi study, eliciting opinions from decision‐makers across all these sectors towards consensus around the key elements of good and bad decision‐making. Participants were first asked to define what makes a ‘good’ and a ‘bad’ decision, and subsequently to identify the top five most important elements of each. While consensus was not found, important insights were identified that can assist improve the standard of decision making at all levels of emergency response and management. We observed (i) a lack of a common understanding between participants of what a decision is, and how a decision differs from pre‐decision and postdecision components; (ii) responses varied according to whether a free text description or the identification of separate elements was requested; (iii) respondents valued ‘goodness’ across different and at times unrelated components a scaled measure of decision quality as opposed to a binary evaluation of ‘rightness’; and (iv) pre‐ and postdecision elements are considered more important than the decision itself when determining the quality of a decision. To address the issues highlighted by the study we recommend improvements in training, and improvements to organization doctrine related to decision making, risk tolerance, assessment of decision quality and development of intent‐based or principle‐based operational guidance. Ultimately, incident controllers from all services must remain cognizant that they will face considerable scrutiny if they cannot explain how they arrived at the decision they made.
Tracking implementation strategies in real‐world settings: VA Office of Rural Health enterprise‐wide initiative portfolio
Authors: Reisinger Heather Schacht , Barron Sheila , Balkenende Erin , Steffen Melissa , Steffensmeier Kenda , Richards Chris , Ball Dan , Chasco Emily E. , Van Tiem Jennifer , Johnson Nicole L. , Jones DeShauna , Friberg Julia E. , Kenney Rachael , Moeckli Jane , Arora Kanika , Rabin Borsika 
Published: September 2024

AbstractObjectiveTo use a practical approach to examining the use of Expert Recommendations for Implementing Change (ERIC) strategies by Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE‐AIM) dimensions for rural health innovations using annual reports on a diverse array of initiatives.Data Sources and Study SettingThe Veterans Affairs (VA) Office of Rural Health (ORH) funds initiatives designed to support the implementation and spread of innovations and evidence‐based programs and practices to improve the health of rural Veterans. This study draws on the annual evaluation reports submitted for fiscal years 2020–2022 from 30 of these enterprise‐wide initiatives (EWIs).Study DesignContent analysis was guided by the RE‐AIM framework conducted by the Center for the Evaluation of Enterprise‐Wide Initiatives (CEEWI), a Quality Enhancement Research Initiative (QUERI)‐ORH partnered evaluation initiative.Data Collection and Extraction MethodsCEEWI analysts conducted a content analysis of EWI annual evaluation reports submitted to ORH. Analysis included cataloguing reported implementation strategies by Reach, Adoption, Implementation, and Maintenance (RE‐AIM) dimensions (i.e., identifying strategies that were used to support each dimension) and labeling strategies using ERIC taxonomy. Descriptive statistics were conducted to summarize data.Principal FindingsA total of 875 implementation strategies were catalogued in 73 reports. Across these strategies, 66 unique ERIC strategies were reported. EWIs applied an average of 12 implementation strategies (range 3–22). The top three ERIC clusters across all 3 years were Develop stakeholder relationships (21%), Use evaluative/iterative strategies (20%), and Train/educate stakeholders (19%). Most strategies were reported within the Implementation dimension. Strategy use among EWIs meeting the rurality benchmark were also compared.ConclusionsCombining the dimensions from the RE‐AIM framework and the ERIC strategies allows for understanding the use of implementation strategies across each RE‐AIM dimension. This analysis will support ORH efforts to spread and sustain rural health innovations and evidence‐based programs and practices through targeted implementation strategies.