bluuebunny/crossref_metadata_2025_split huggingface dataset:
The thermodynamic state of aerobic glycolytic flux plays a critical role in stabilizing aerobic glycolytic flux of cancer cells
Authors: Jin Chengmeng , Hu Wei , Wang Yuqi , Wu Hao , Zeng Siying , Ying Minfeng , Hu Xun 
Published: July 2022

AbstractInhibition of aerobic glycolysis (AG) is a strategy for cancer treatment, but its clinical translation has not been successful, suggesting that the mechanism underlying the inhibition of AG is not completely understood. We introduce thermodynamic state of AG (TSAG) into AG flux control, which refers the actual change of Gibbs free energy (ΔG) of reactions along the pathway. By using PKM2 knockdown and knockout models, we found that TSAG is resistant to PKM2 perturbation and it can effectively counteract the inhibitory effect of PKM2 perturbation on AG flux. Moreover, we deciphered the interrelationship between TSAG, AG rate, intermediate concentrations, and PK activity, revealed that TSAG is a system property of AG independent of cancer cells’ pathophysiological features and it plays important roles in stabilizing AG flux responding to perturbation. We propose that both inhibition of glycolytic enzyme and disruption of TSAG are required for effective AG inhibition.
Rescue of alveolar wall liquid secretion blocks fatal lung injury by influenza-staphylococcal coinfection
Authors: Tang Stephanie , De Jesus Ana Cassandra , Chavez Deebly , Suthakaran Sayahi , Moore Sarah K. L. , Rathnasinghe Raveen , Schotsaert Michael , Bhattacharya Jahar , Hook Jaime L. 
Published: July 2022

ABSTRACTSecondary lung infection by inhaled Staphylococcus aureus (SA) is a common and lethal event in individuals infected with influenza A virus (IAV). It is unclear how IAV disrupts host defense to promote SA infection in lung alveoli, where fatal lung injury occurs. We addressed this issue using the first real-time determinations of alveolar responses to IAV in live, intact, perfused lungs. Our findings show IAV infection blocked defensive alveolar wall liquid (AWL) secretion and induced airspace liquid absorption, thereby reversing normal alveolar liquid dynamics and inhibiting alveolar clearance of inhaled bacteria. Loss of AWL secretion resulted from dephosphorylation, hence inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in alveolar epithelium, and airspace liquid absorption was caused by alveolar epithelial stimulation of the epithelial Na+ channel (ENaC). Loss of AWL secretion promoted alveolar stabilization by SA and alveolar damage by the secreted SA toxin, alpha hemolysin, but rescue of AWL secretion protected against fatal SA-induced lung injury in IAV-infected mice. These findings reveal a central role for AWL secretion in alveolar defense against inhaled bacteria and identify AWL inhibition as a critical mechanism of IAV lung pathogenesis. AWL rescue may represent a new therapeutic approach for IAV-SA coinfection.GRAPHICAL ABSTRACT
Age-associated changes in knee osteoarthritis, pain-related behaviors, and dorsal root ganglia immunophenotyping of male and female mice
Authors: Geraghty Terese , Obeidat Alia M. , Ishihara Shingo , Wood Matthew J. , Li Jun , Lopes Erika Barboza Prado , Scanzello Carla R. , Griffin Timothy M. , Malfait Anne-Marie , Miller Rachel E. 
Published: July 2022

AbstractObjectiveOsteoarthritis (OA) is a leading cause of chronic pain, yet OA pain management remains poor. Age is the strongest predictor of OA development, and mechanisms driving OA pain are unclear. While injury-induced OA models are useful, only a subset of OA is linked to traumatic injury. Here, we aimed to characterize age-associated joint damage, mechanical sensitization, and dorsal root ganglia (DRG) immune phenotypes in mice of both sexes.MethodsMale or female mice aged 6- or 20-months old were evaluated for histopathologic knee OA, pain-related behaviors, and L3-L5 dorsal root ganglia (DRG) immune characterization via flow cytometry. DRG gene expression in aged mice and humans was also examined.ResultsTwenty-month old male mice had worse cartilage degeneration than 6-month old mice. Older female knees showed increased cartilage degeneration, but to a lesser degree than males. Older mice of both sexes had worse mechanical allodynia, knee hyperalgesia, and grip strength compared to younger mice. For both sexes, DRGs from older mice showed decreased CD45+ cells, and a significant increase in F4/80+ macrophages and CD11c+ dendritic cells. Older male DRGs showed increased expression of Ccl2 and Ccl5 and older female DRGs showed increased Cxcr4 and Ccl3 compared to 6-month DRGs, among other differentially expresssed genes. Human DRG analysis from six individuals >80 years old revealed elevated CCL2 in male DRGs compared to females, whereas CCL3 was higher in female DRGs.ConclusionsHere we show that aging in male and female mice is accompanied by mild knee OA, mechanical sensitization, and changes to immune cell populations in the DRG, suggesting novel avenues for development of analgesic therapies.
A 96-WELL VALVED MICROFLUIDIC DEVICE FOR TESTING OF LIVE INTACT TUMOR CUBOIDS
Authors: Lockhart Ethan J. , Horowitz Lisa F. , Lim Cb , Nguyen Tran , Mehrabi Mehdi , Gujral Taranjit S. , Folch Albert 
Published: July 2022

ABSTRACTThere is a pressing need for functional testing platforms that use human, live tumor tissue to better predict traditional and immunotherapy responses. Such platforms should also retain as much of the native tumor microenvironment (TME) as possible, as many cancer drug actions rely on TME-dependent mechanisms. Present high-throughput testing platforms that have some of these features, e.g. based on patient-derived tumor organoids, require a growth step that alters the TME. On the other hand, micro-dissected tumor tissue “spheroids” that retain an intact TME have shown promising responses to immunomodulators acting on native immune cells. Here we demonstrate a microfluidic 96-well platform designed for drug treatment of hundreds of similarly-sized, cuboidal micro-tissues (“cuboids”) produced from a single tumor sample. Four cuboids per well are automatically arrayed into the platform using hydrodynamic trapping. The microfluidic device, entirely fabricated in thermoplastics, features microvalves that fluidically isolate each well after the cuboid loading step. Since the platform effectively makes the most of scarce tumor tissue, we believe it could ultimately be applied to human biopsies for drug discovery and personalized oncology, altogether bypassing animal testing.
RNA polymerase II and PARP1 shape enhancer-promoter contacts
Authors: Barshad Gilad , Lewis James J. , Chivu Alexandra G. , Abuhashem Abderhman , Krietenstein Nils , Rice Edward J. , Rando Oliver J. , Hadjantonakis Anna-Katerina , Danko Charles G. 
Published: July 2022

AbstractHow enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we studied enhancer-promoter contact architecture and communication by integrating data from nucleosome-resolution genomic contact maps, nascent transcription, and perturbations to transcription-associated proteins and thousands of candidate enhancers. Contact frequency between functionally validated enhancer-promoter pairs was most enriched near the +1 and +2 nucleosomes at enhancers and target promoters, indicating that functional enhancer-promoter pairs spend time in close physical proximity. Blocking RNA polymerase II (Pol II) caused major disruptions to enhancer-promoter contacts. Paused Pol II occupancy and the enzymatic activity of poly (ADP-ribose) polymerase 1 (PARP1) stabilized enhancer-promoter contacts. Based on our findings, we propose an updated model that couples transcriptional dynamics and enhancer-promoter communication.
CBP60-DB: An AlphaFold-predicted plant kingdom-wide database of the CALMODULIN-BINDING PROTEIN 60 (CBP60) protein family with a novel structural clustering algorithm
Authors: Amani Keaun , Shivnauth Vanessa , Castroverde Christian Danve M. 
Published: July 2022

AbstractMolecular genetic analyses in the model speciesArabidopsis thalianahave demonstrated the major roles of different CAM-BINDING PROTEIN 60 (CBP60) proteins in growth, stress signaling, and immune responses. Prominently, CBP60g and SARD1 are paralogous CBP60 transcription factors that regulate numerous components of the immune system, such as cell surface and intracellular immune receptors, MAP kinases, WRKY transcription factors, and biosynthetic enzymes for immunity-activating metabolites salicylic acid (SA) andN-hydroxypipecolic acid (NHP). However, their function, regulation and diversification in most species remain unclear. Here we have created CBP60-DB, a structural and bioinformatic database that comprehensively characterized 1052CBP60gene homologs (encoding 2376 unique transcripts and 1996 unique proteins) across 62 phylogenetically diverse genomes in the plant kingdom. We have employed deep learning-predicted structural analyses using AlphaFold2 and then generated dedicated web pages for all plant CBP60 proteins. Importantly, we have generated a novel clustering visualization algorithm to interrogate kingdom-wide structural similarities for more efficient inference of conserved functions across various plant taxa. Because well-characterized CBP60 proteins inArabidopsisare known to be transcription factors with putative calmodulin-binding domains, we have integrated external bioinformatic resources to analyze protein domains and motifs. Collectively, we present a plant kingdom-wide identification of this important protein family in a user-friendly AlphaFold-anchored database, representing a novel and significant resource for the broader plant biology community.
Cortico-cerebellar coordination facilitates neuroprosthetic control
Authors: Abbasi Aamir , Rangwani Rohit , Bowen Daniel W. , Fealy Andrew W. , Danielsen Nathan P. , Gulati Tanuj 
Published: July 2022

AbstractTemporal coordination among neurons and development of functional neuronal assemblies is central to nervous system function and purposeful behavior. Still, there is a paucity of evidence about how functional coordination emerges in task-related neuronal assemblies in cortical and subcortical regions that are related to the control of functional output. We investigated emergent neural dynamics between primary motor cortex (M1) and the contralateral cerebellar cortex as rats learned a neuroprosthetic/ brain machine interface (BMI) task. BMIs offer a powerful tool to causally test how distributed neural networks achieve specific neural activation. During neuroprosthetic learning, actuator movements are causally linked to primary motor cortex (M1) neurons, i.e.,“direct”neurons, that drive the decoder and whose firing is required to successfully perform the task. However, it is unknown how task-relatedM1activity interacts with cerebellar activity. We observed a striking 3–6 Hz coherence that emerged between these regions’ local–field potentials (LFPs) with neuroprosthetic learning which also modulated task-related spiking. We found a robust task-related indirect modulation in the cerebellum, and we found that this activity developed a preferential relationship withM1task-related direct and indirect activity but not with M1 task unrelated activity with learning. We also performed optogenetic inhibition of cerebellar activity (in the cerebellar cortex and its deep nuclei) and found that this led to performance impairments inM1–driven neuroprosthetic control. Together, these results demonstrate that coordinated neural dynamics emerge in cortico-cerebellar regions during neuroprosthetic learning which supports task-relevant activity inM1neuronal populations, and further, that cerebellar influence is necessary forM1–driven neuroprosthetic control.
Carbohydrate-Binding Protein from Stinging Nettle as Fusion Inhibitor for SARS-CoV-2 Variants of Concern
Authors: Vanhulle Emiel , D’huys Thomas , Provinciael Becky , Stroobants Joren , Camps Anita , Noppen Sam , Schols Dominique , Van Damme Els J.M. , Maes Piet , Stevaert Annelies , Vermeire Kurt 
Published: July 2022

AbstractUrtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks entry of pseudotyped SARS-CoV-2 in A549.ACE2+-TMPRSS2 cells, with IC50 values ranging from 0.32 to 1.22 µM. Furthermore, UDA prevents viral replication of the early Wuhan-Hu-1 strain in Vero E6 cells (IC50 = 225 nM), but also the replication of SARS-CoV-2 variants of concern, including Alpha, Beta and Gamma (IC50 ranging from 115 to 171 nM). In addition, UDA exerts antiviral activity against the latest circulating Delta and Omicron variant in U87.ACE2+ cells (IC50 values are 1.6 and 0.9 µM, respectively). Importantly, when tested in Air-Liquid Interface (ALI) primary lung epithelial cell cultures, UDA preserves antiviral activity against SARS-CoV-2 (20A.EU2 variant) in the nanomolar range. Surface plasmon resonance (SPR) studies demonstrated a concentration-dependent binding of UDA to the viral spike protein of SARS-CoV-2, suggesting interference of UDA with cell attachment or subsequent virus entry. Moreover, in additional mechanistic studies with cell-cell fusion assays, UDA inhibited SARS-CoV-2 spike protein-mediated membrane fusion. Finally, pseudotyped SARS-CoV-2 mutants with N-glycosylation deletions in the S2 subunit of the spike protein remained sensitive to the antiviral activity of UDA. In conclusion, our data establish UDA as a potent and broad-spectrum fusion inhibitor for SARS-CoV-2.
A DEA-ANN-based analytical framework to assess and predict the efficiency of Canadian universities in a service supply chain context
Authors: Jauhar Sunil Kumar , Zolfagharinia Hossein , Amin Saman Hassanzadeh 
Published: July 2022

PurposeThis research is about embedding service-based supply chain management (SCM) concepts in the education sector. Due to Canada's competitive education sector, the authors focus on Canadian universities.Design/methodology/approachThe authors develop a framework for evaluating and forecasting university performance using data envelopment analysis (DEA) and artificial neural networks (ANNs) to assist education policymakers. The application of the proposed framework is illustrated based on information from 16 Canadian universities and by investigating their teaching and research performance.FindingsThe major findings are (1) applying the service SCM concept to develop a performance evaluation and prediction framework, (2) demonstrating the application of DEA-ANN for computing and predicting the efficiency of service SCM in Canadian universities, and (3) generating insights to enable universities to improve their research and teaching performances considering critical inputs and outputs.Research limitations/implicationsThis paper presents a new framework for universities' performance assessment and performance prediction. DEA and ANN are integrated to aid decision-makers in evaluating the performances of universities.Practical implicationsThe findings suggest that higher education policymakers should monitor attrition rates at graduate and undergraduate levels and provide financial support to facilitate research and concentrate on Ph.D. programs. Additionally, the sensitivity analysis indicates that selecting inputs and outputs is critical in determining university rankings.Originality/valueThis research proposes a new integrated DEA and ANN framework to assess and forecast future teaching and research efficiencies applying the service supply chain concept. The findings offer policymakers insights such as paying close attention to the attrition rates of undergraduate and postgraduate programs. In addition, prioritizing internal research support and concentrating on Ph.D. programs is recommended.
Local habitus and temporal overtourism in Yogyakarta
Authors: Purwandani Intan , Pakan Sarani Pitor 
Published: July 2022

Purpose
This paper aims to unpack personal narratives of local residents in relation to the effects of overtourism in Yogyakarta, Indonesia. The paper uses Pierre Bourdieu’s concept of habitus to understand how local residents cope with temporal overtourism.

Design/methodology/approach
Findings were gathered from observations and interviews. Interviews were conducted with 12 informants, consisting of local small-to-medium enterprise tourism entrepreneurs, local informal tourism workers and a group of locals uninvolved in tourism.

Findings
The paper has two key findings. First, locals uninvolved in tourism show empathetic behavior toward the locals involved in tourism despite their experiencing negative effects of tourism. The involved locals, for their part, were aware of the importance of resolving issues with the uninvolved locals through regular communication so as to secure the sustained future of tourism. Second, the use of social capital by involved and uninvolved locals reflects the local Javanese culture and value system in which social harmony and integration are paramount.

Research limitations/implications
Local habitus forms and informs locals’ perceptions on temporal overtourism issues. It enables an understanding on how locals manage the effects of overtourism in Yogyakarta. The habitus, which is greatly influenced by Javanese values, creates attitudes and behaviors which are empathetic and tolerant.

Practical implications
To avoid the potential conflict when overtourism explicitly or implicitly frustrates locals, policy should be formulated by taking into account the findings of this paper on the local habitus. The study contributes to the overtourism debate by looking at the inter-relationship of local social structures and cultural context with local responses to temporal overtourism.

Originality/value
Using the concept of habitus, this research deepens existing understanding on the local responses toward overtourism. This research expects to theoretically enrich and complexify debates on tourism–habitus nexus in tourism studies.
Regulatory-focused job crafting, person-job fit and internal employability–examining interrelationship and underlying mechanism
Authors: Sameer Sanjeet Kumar , Priyadarshi Pushpendra 
Published: July 2022

PurposeThis paper examines the relationships between regulatory-focused job crafting, i.e. promotion- and prevention-focused job crafting, person-job fit and internal employability and explores the direct and underlying mediation process using conservation of resources and job demands-resources theories.Design/methodology/approachSurvey data collected from 425 executives of India based public sector enterprises were used to test hypotheses.FindingsPromotion- and prevention-focused job crafting respectively had a contrasting relationship with needs-supplies fit. The relationship with demands-abilities fit was statistically significant only in the case of prevention-focused job crafting. These two job crafting forms respectively had a positive and a negative effect on internal employability, both directly as well as indirectly through person-job fit.Practical implicationsEmployees can pursue promotion-focused job crafting and avoid prevention-focused job crafting to improve their person-job fit as well as internal employability which subsequently may have multiple favourable outcomes at an organizational and individual level.Originality/valueThe study, for the first time, empirically investigates the differential role of individuals' efforts in the form of promotion- and prevention-focused job crafting, in influencing internal employability and explains its underlying mechanism through person-job fit. These interrelationships may have important implications for employees' job demand management process and job choices.
Client and contractor perspectives on attributes affecting construction quality in a war-affected region
Authors: Zaray Abdul Habib , Hasan Abid , Johari Sparsh , Hashmat Parvez Ahmad , Jha Kumar Neeraj 
Published: July 2022

PurposeThe poor quality of construction work in war-affected regions is a significant issue. The large-scale destruction to the existing infrastructure from the war necessitates cost and time-efficient delivery of construction projects during and post-war to bring normalcy to affected lives and places. Consequently, there is always a tendency to finish construction projects in the shortest possible time on a limited budget without following the proper quality management processes. However, the poor quality of construction projects continues to affect the country's development, growth, credibility, reputation, and public safety for several years after the war. To this end, the present study was conducted to evaluate the significant attributes and factors contributing to the poor quality of construction projects in the war-affected Afghan construction sector.Design/methodology/approachA total of 31 attributes influencing construction project quality were ranked based on 110 completed survey responses collected from Afghan construction professionals. Moreover, independent samples t-test, Spearman's rank correlation test, and exploratory factor analysis were conducted.FindingsThe study found a moderate consensus between clients and contractors on attributes' rankings. In addition, the independent samples t-test showed statistically significant differences in means values of responses from clients and contractors for eight attributes. Based on factor analysis, 19 important attributes (median value greater than or equal to four) were classified into 4 latent factors – (1) poor-quality assurance and control, (2) unethical practices, (3) design and drawing errors, and (4) knowledge and skills gap.Originality/valueEvaluating the factors affecting the quality of construction projects will help clients, government departments, and construction practitioners improve the construction quality management practices. The findings will also inform the policies and procedures of international aid providers.