bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation
Authors: Walters Hannah E. , Troyanovskiy Konstantin , Yun Maximina H. 
Published: September 2022

AbstractSalamanders are able to regenerate their entire limbs throughout lifespan, through a process that involves significant modulation of cellular plasticity. Limb regeneration is accompanied by the induction of cellular senescence, a state of irreversible cell cycle arrest associated with profound non-cell-autonomous consequences. While traditionally associated with detrimental physiological effects, here we show that senescent cells enhance newt limb regeneration. Through a lineage tracing approach, we demonstrate that senescent cells promote dedifferentiation of mature muscle tissue to generate regenerative progenitors. In a paradigm of newt myotube dedifferentiation, we uncover that senescent cells promote myotube cell cycle re-entry and reversal of muscle identity via secreted factors. Transcriptomic profiling and loss of function approaches identify the FGF-ERK signalling axis as a critical mediator of senescence-induced muscle plasticity. While chronic senescence constrains muscle regeneration in physiological mammalian contexts, we thus highlight a beneficial role for cellular senescence as an important modulator of dedifferentiation, a key mechanism for regeneration of complex structures.
Cancer-Associated Mutations Enhance The Sensitivity Of The Trupath GαQ/11 System
Authors: Safitri Dewi , Harris Matthew , Pearce Abigail , Huang Xianglin , Rosa Matthew , Barkan Kerry , Wills Edward , Marti-Solano Maria , Falk Matthew D. , Ladds Graham 
Published: September 2022

ABSTRACTG protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and are a common drug target. They can be stabilised in different conformational states by ligands to activate multiple transducers and effectors leading to a variety of cellular responses. The potential of agonists to activate select pathways has important implications for drug discovery. Thus, there is a clear need to profile the initial GPCR signal transduction event, activation of G proteins, to enhance understanding of receptor coupling and guide drug design. The BRET-based biosensor suite, TRUPATH, was recently developed to enable quantification of the activation profiles of all non-visual G proteins (excluding Golf and G14) and has since been utilised in numerous studies. However, it fails to detect Gq/11 activation for a number of GPCRs previously reported to display promiscuous secondary coupling to Gq/11. Here we report modifications to the Gαq and Gα11 biosensors in the switch I region that prevent intrinsic GTPase activity (R183C/Q). Except for the PAC1R, substitution with cancer-associated mutations, Cys or Gln, significantly increased sensitivity to allow detection of robust, reliable, and representative Gq/11 responses to Class B1 GPCRs. We also demonstrate the utility of these modified biosensors for promiscuously coupled class A GPCR that have primary Gs-coupling. Thus, we propose that modification to Gαq/11 may also be necessary in other biosensor systems to enable detection of Gq/11 activation.
Small molecule G-quadruplex ligands are antibacterial candidates for Gram-negative bacteria
Authors: Takebayashi Yuiko , Ramos-Soriano Javier , Jiang Y. Jennifer , Samphire Jennifer , Belmonte-Reche Efres , O’Hagan Michael P. , Gurr Catherine , Heesom Kate J. , Lewis Philip A. , Samernate Thanadon , Nonejuie Poochit , Spencer James , Galan M. Carmen 
Published: September 2022

ABSTRACTThere is great need for novel strategies to tackle antimicrobial resistance, in particular in Gram-negative species such asEscherichia colithat cause opportunistic infections of already compromised patients. Here we demonstrate, following a screen of G-quadruplex (G4) ligand candidates, that a novel pyridinium-functionalized azobenzeneL9shows promising antibacterial activity (MIC values ≤ 4 μg/mL) against multi-drug resistantE. coli. Tandem Mass Tag (TMT) proteomics ofE. colitreated with sub-lethal concentrations ofL9, identified that, consistent with its superior antibacterial activity,L9treatment influences expression levels of more G4-associated proteins than the analogous ligandsL5(stiff-stilbene) or pyridostatin (PDS), and upregulates multiple essential proteins involved in translation. Biophysical analysis showedL9binds potential target G4-containing sequences, identified from proteomic experiments and by bioinformatics, with variable affinity, in contrast to the two comparator G4 ligands (L5, PDS) that better stabilize G4 structures but have lower antimicrobial activity. Fluorescence microscopy-based Bacterial Cytological Profiling (BCP) suggests that theL9mechanism of action is distinct from other antibiotic classes. These findings support strategies discovering potential G4 ligands as antibacterial candidates for priority targets such as multi-drug resistantE. coli, warranting their further exploration as potential novel therapeutic leads with G4-mediated modes of action.Abstract Figure
Global characterization of gene expression in the brain of starved immature R. prolixus
Authors: Nevoa Jessica Coraiola , Latorre-Estivalis Jose Manuel , Pais Fabiano Sviatopolk-Mirsky , Marliére Newmar Pinto , Fernandes Gabriel da Rocha , Lorenzo Marcelo Gustavo , Guarneri Alessandra Aparecida 
Published: September 2022

AbstractBackground: Rhodnius prolixus is a vector of Chagas disease and has become a model organism to study physiology, behavior, and pathogen interaction. The publication of its genome allowed initiating a process of comparative characterization of the gene expression profiles of diverse organs exposed to varying conditions. Brain processes control the expression of behavior and, as such, mediate immediate adjustment to a changing environment, allowing organisms to maximize their chances to survive and reproduce. The expression of fundamental behavioral processes like feeding requires a fine control in triatomines because they obtain their blood meals from potential predators. Therefore, the characterization of gene expression profiles of key components modulating behavior in brain processes, like those of neuropeptide precursors and their receptors, seems fundamental. Here we study global gene expression profiles in the brain of starved R. prolixus fifth instar nymphs by means of RNASeq sequencing. Results: The expression of neuromodulatory genes such as those of precursors of neuropeptides, neurohormones, and their receptors; as well as the enzymes involved in the biosynthesis and processing of neuropeptides and biogenic amines were fully characterized. Other important gene targets such as neurotransmitter receptors, nuclear receptors, clock genes, sensory receptors, and takeouts were identified and their gene expression analyzed. Conclusion: We propose that the set of neuromodulation-related genes highly expressed in the brain of starved R. prolixus nymphs deserves functional characterization to allow the subsequent development of tools targeting them for bug control. As the brain is a complex structure that presents functionally-specialized areas, future studies should focus on characterizing gene expression profiles in target areas, e.g. mushroom bodies, to complement our current knowledge.
Photosystem II monomeric antenna CP26 has a key role in Non-Photochemical Quenching inChlamydomonas reinhardtii
Authors: Cazzaniga Stefano , Kim Minjae , Pivato Matteo , Perozeni Federico , Sardar Samim , D’Andrea Cosimo , Jin EonSeon , Ballottari Matteo 
Published: September 2022

SUMMARYThermal dissipation of the excitation energy harvested in excess, named non-photochemical quenching (NPQ), is one of the main photoprotective mechanisms evolved in oxygenic photosynthetic organisms. Here, the specific function in photoprotection and light harvesting of the monomeric Photosystem II antenna CP26, was investigated inChlamydomonas, model organism for green algaeCRISPR/Cas9 genome editing and complementation strategies were applied to generate newcp26knock-out mutants (namedk6#) that differently from previous findings, did not negatively affected CP29 accumulation, allowing to compare mutants specifically deprived of CP26, CP29 or bothThe absence of CP26 partially affected Photosystem II activity causing a reduced growth at low or medium light but not at high irradiances. However, the main phenotype observed in k6# mutants was a more than 70% reduction of NPQ compared to wild-type. This NPQ phenotype could be fully rescued by genetic complementation demonstrating that ∼50% of CP26 content compared to wild-type was sufficient to restore the NPQ capacity.Our findings demonstrate a pivotal role for CP26 in NPQ induction while CP29 has a crucial function for Photosystem II activity. The genetic engineering of these two proteins could be a promising strategy to regulate photosynthetic efficiency of microalgae under different light regimes.
Natural recombination among Type I restriction-modification systems creates diverse genomic methylation patterns among Xylella fastidiosa strains
Authors: O’Leary Michael L. , Burbank Lindsey P. 
Published: September 2022

AbstractXylella fastidiosa is an important bacterial pathogen of plants causing high consequence diseases in agricultural crops around the world. Although as a species X. fastidiosa can infect an extremely broad range of host plants, significant variability exists between strains and subspecies groups in virulence on specific host plant species, and other traits such as growth habits. Natural competence and horizontal gene transfer are believed to occur frequently in X. fastidiosa, and likely influences the evolution of this pathogen. However, some X. fastidiosa strains are extremely difficult or impossible to manipulate genetically using standard transformation techniques. Several restriction-modification systems are encoded in the X. fastidiosa genome, including multiple Type I R-M systems that may influence horizontal gene transfer and recombination. In this study, several conserved Type I R-M systems were compared across 129 X. fastidiosa genome assemblies representing all known subspecies and 32 sequence types. Considerable allelic variation among strains was identified among the single specificity subunit (hsdS) of each Type I R-M system, with a unique hsdS allele profile generally conserved within a monophyletic cluster of strains. Inactivating mutations were identified in Type I R-M systems of specific strains, showing heterogeneity in the complement of functional Type I R-M systems across X. fastidiosa. Genomic DNA methylation patterns were characterized in 20 X. fastidiosa strains and associated with Type I R-M system allele profiles. Overall, this study describes epigenetic modifications in X. fastidiosa associated with functional Type I R-M systems and characterizes the diversity in these systems across X. fastidiosa lineages.ImportanceEconomic impacts on agricultural production due to X. fastidiosa have been severe in the Americas, Europe, and parts of Asia. Despite a long history of research on this pathogen, certain fundamental questions regarding the biology, pathogenicity, and evolution of X. fastidiosa have still not been answered. Wide scale whole genome sequencing has begun to provide a more insight into X. fastidiosa genetic diversity and horizontal gene transfer but the mechanics of genomic recombination in natural settings and extent to which this directly influences bacterial phenotypes such as plant host range are not well understood. Genome methylation is an important factor in horizontal gene transfer and bacterial recombination that has not been comprehensively studied in X. fastidiosa. This study characterizes methylation associated with Type I restriction-modification systems across a wide range of X. fastidiosa strains and lays the groundwork for a better understanding of X. fastidiosa biology and evolution through epigenetics.
Malaria prevention knowledge, attitudes, and practices (KAP) among adolescents living in an area of persistent transmission in Senegal: Results from a cross-sectional study
Authors: Tairou Fassiatou , Nawaz Saira , Tahita Marc Christian , Herrera Samantha , Faye Babacar , Tine Roger C K 
Published: September 2022

AbstractIntroductionWhile malaria morbidity has sharply declined in several areas in Senegal, it remains an important problem in the southern part of the country, particularly among adolescents. Understanding adolescents’ knowledge, attitudes, prevention and care-seeking practices is important to inform more targeted interventions aimed at optimizing adolescents’ uptake of malaria prevention and control measures. This study assessed malaria-related knowledge, attitudes, and practices (KAP) among adolescents living in a highly persistent transmission area in Senegal.MethodsA community-based cross-sectional survey was conducted among 391 adolescents living in the Saraya health district. A multistage random sampling technique was used to select households. An electronic questionnaire developed on Open Data Kit (ODK), was used to collect data on socio-demographic characteristics, household assets, adolescents’ knowledge of malaria, as well as their attitudes with regards to malaria prevention, and care-seeking behaviors. Bivariate and multivariate analyses were performed to assess factors associated with adolescents’ KAP towards malaria.ResultsNearly, one-third of the participants had good knowledge of malaria (34.4%) and good practice in regards to malaria preventive measures (32.8%) while approximately three-quarters had a positive attitude (75.1%) and good care-seeking behavior (73.8%) regarding malaria. Multivariate analysis revealed that a primary (aOR=5.43, p=0.002) or secondary level of education (aOR=10.41, p=0.000) was associated with good knowledge of malaria transmission, signs, and prevention measures. Male individuals had lower knowledge compared to female ones (aOR=0.40, p=0.001). Individuals belonging to households from the fourth (aOR=0.29, p=0.015), second (OR=0.13, p=0.000), and lowest (aOR=0.18, p=0.001) wealth quintiles were less likely to have a positive attitude towards malaria compared to those from households in the highest wealth quintile. A positive attitude was two times more likely to be (aOR=2.32, p=0.011) associated with good practice of prevention measures compared to adolescents who demonstrated negative attitudes. Individuals from households in the fourth (aOR=0.40, p=0.018), middle (aOR=0.32, P=0.03), and second (aOR=0.44, p=0.035) wealth quintiles were less likely to use malaria prevention measures compared to those from households in the highest wealth quintile.ConclusionThe study revealed that adolescents, generally have poor levels of malaria knowledge and low uptake of malaria prevention and control interventions. Targeted interventions for high-risk adolescents are needed, that focus on improving their knowledge of the disease and effective preventive measures, and on increasing their access to health care services and LLINs.
Effects of CFTR Modulators on Serum Biomarkers of Liver Fibrosis in Children with Cystic Fibrosis
Authors: Levitte Steven , Fuchs Yonathan , Wise Russell , Sellers Zachary M. 
Published: September 2022

ABSTRACTThe cystic fibrosis transmembrane conductance regulator (CFTR) corrector/potentiator combinations lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor improve sweat chloride, pulmonary function, and nutrition. Yet it is unclear whether they may also impact the progression of liver fibrosis, which is a substantial source of morbidity and mortality for patients with cystic fibrosis (CF). We conducted a retrospective, single-center analysis of children and adolescents with CF treated with lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor therapy, focusing on alterations in liver function tests and fibrosis indices using previously-established thresholds that corresponded with increased liver elastography. In pairwise comparisons of before and during treatment timepoints, we found that those with CF-associated liver involvement experienced significant decreases in gamma-glutamyl transferase (GGT), AST-to-Platelet Index (APRI), and GGT-to-Platelet Ratio (GPR) while on lumacaftor/ivacaftor. These differences were not observed in patients treated with elexacaftor/tezacaftor/ivacaftor, nor were they observed in patients without underlying CF-associated liver disease. These results provide the first evidence that lumacaftor/ivacaftor may improve liver fibrosis in children and adolescents with CF and suggest it may be beneficial in the treatment of CF-associated liver disease.
Novel monoclonal antibodies showing broad neutralizing activity for SARS-CoV-2 variants including Omicrons BA.5 and BA.2.75
Authors: Ishimaru Hanako , Nishimura Mitsuhiro , Tjan Lidya Handayani , Sutandhio Silvia , Marini Maria Istiqomah , Effendi Gema Barlian , Shigematsu Hideki , Kato Koji , Hasegawa Natsumi , Aoki Kaito , Kurahashi Yukiya , Furukawa Koichi , Shinohara Mai , Nakamura Tomoka , Arii Jun , Nagano Tatsuya , Nakamura Sachiko , Sano Shigeru , Iwata Sachiyo , Mori Yasuko 
Published: September 2022

SummaryWe identified novel neutralizing monoclonal antibodies against SARS-CoV-2 variants (including Omicron) from individuals received two doses of mRNA vaccination after they had been infected with wildtype. We named them MO1, MO2 and MO3. MO1 shows high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, and BA.2.75 and BA.5. Our findings confirm that the wildtype-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants (including BA.5 and BA.2.75). The monoclonal antibodies obtained herein could serve as novel prophylaxis and therapeutics against not only current SARS-CoV-2 viruses but also future variants that may arise.
The HyDAPI framework: a versatile tool integrating Lean Six Sigma and digitalisation for improved quality management in Industry 4.0
Authors: Clancy Rose , Bruton Ken , O’Sullivan Dominic T.J. , Cloonan Aidan J. 
Published: September 2022

Purpose
Quality management practitioners have yet to cease the potential of digitalisation. Furthermore, there is a lack of tools such as frameworks guiding practitioners in the digital transformation of their organisations. The purpose of this study is to provide a framework to guide quality practitioners with the implementation of digitalisation in their existing practices.

Design/methodology/approach
A review of literature assessed how quality management and digitalisation have been integrated. Findings from the literature review highlighted the success of the integration of Lean manufacturing with digitalisation. A comprehensive list of Lean Six Sigma tools were then reviewed in terms of their effectiveness and relevance for the hybrid digitisation approach to process improvement (HyDAPI) framework.

Findings
The implementation of the proposed HyDAPI framework in an industrial case study led to increased efficiency, reduction of waste, standardised work, mistake proofing and the ability to root cause non-conformance products.

Research limitations/implications
The activities and tools in the HyDAPI framework are not inclusive of all techniques from Lean Six Sigma.

Practical implications
The HyDAPI framework is a flexible guide for quality practitioners to digitalise key information from manufacturing processes. The framework allows organisations to select the appropriate tools as needed. This is required because of the varying and complex nature of organisation processes and the challenge of adapting to the continually evolving Industry 4.0.

Originality/value
This research proposes the HyDAPI framework as a flexible and adaptable approach for quality management practitioners to implement digitalisation. This was developed because of the gap in research regarding the lack of procedures guiding organisations in their digital transition to Industry 4.0.
Green leadership and pro-environmental behaviour: a moderated mediation model with rewards, self-efficacy and training
Authors: Ahuja Jaya , Yadav Mohit , Sergio Rommel P. 
Published: September 2022

PurposeThe purpose of this study is to identify the association between environmental leadership (EL) and pro-environmental behaviour among the middle-level employees in iron and steel manufacturing companies. The study further emphasizes on mediation of the relationship by green rewards and green self-efficacy in EL and pro-environmental behaviour relationship, moderated by green training.Design/methodology/approachTo find the reliability and validity of the model, confirmatory factor analysis was used. Pearson correlation was used to explore the relationship between variables. PROCESS macro of Hayes (2013) Model 14 was used to test mediation and moderated mediation.FindingsEL influenced pro-environmental behaviour in middle-level employees. Green rewards and green self-efficacy mediated the relationship. Green training moderated the mediated relationship of green rewards and green self-efficacy between EL and pro-environmental behaviour.Originality/valueThis is a fresh contribution around EL and pro-environmental behaviour in iron and steel companies; however, there are studies available on this relationship, but the unique contribution of the study is studying EL in iron and steel companies and mediated moderated relationship by green rewards, self-efficacy and training. It is necessary for the organizations to develop environmental leaders to promote pro-environmental behaviour in employees across sectors.
How augmented reality can enhance fashion retail: a UX design perspective
Authors: Xue Liangchao , Parker Christopher J. , Hart Cathryn A. 
Published: September 2022

PurposeTo develop compelling augmented reality (AR) experiences, this paper aims to examine AR value to physical fashion retail, defines the most effective form (e.g. app vs magic mirror) and assesses AR’s impact on consumer behaviour.Design/methodology/approachThis study comprises two phases. Phase one conducted three co-design workshops with 15 participants (aged 18–34) to evaluate current shopping modes and discover design opportunities. Phase two designed two AR prototypes (AR Branded App and Magic Mirror) and evaluated the prototypes through experience prototype experiments with 42 participants.FindingsParticipants have a positive attitude towards AR shopping adoption, improving consumer satisfaction and boosting purchase intention. AR technology can be the value in enjoyment to make the shopping experience more fun. However, no participants thought entertainment would trigger their intention to use AR. Therefore, designing useful AR apps that provide substantial functional benefits with enjoyment-oriented elements will encourage consumers to engage in high-street physical retail. In this way, consumers can interact with products and receive more information. AR can help luxury brands tell a story from a hedonic perspective, enabling consumers to engage with the story while maintaining human interaction to ensure an elevated level of service quality.Originality/valueThis study devises six design requirements to guide innovators and retailers in creating AR retail environments that satisfy their customer’s desires.