bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of BACH1 by hemin improves cardiac function in a mouse model of myocardial infarction
Authors: Alvino Valeria , Katare Rajesh , Fricker Annabell , Avolio Elisa , Caputo Massimo , Madeddu Paolo , Slater Sadie 
Published: October 2023

AbstractAimsThe BTB and CNC homology 1 (BACH1) transcription factor is a repressor of heme oxygenase-1 (HMOX1), a pivotal enzyme involved in antioxidant response and iron recycling. Here we investigated whether pharmacological modulation of the BACH1 by hemin impacts on antioxidant responses and reparative angiogenesis in a mouse model of myocardial infarction (MI).Methods and resultsIn vitrostudies on vascular cells showed hemin treatment downregulates BACH1 gene and protein expression and upregulates HMOX1. This axis was confirmed to be modulated in the murine infarcted heart, with BACH1 being upregulated, and HMOX1 downregulated compared to sham. Treatment with hemin every 3 days for 28 days post-MI significantly decreased BACH1 and increased HMOX1 protein expression, though no decrease in oxidative stress markers was detected. Hemin treated mice showed increases in both capillary and arteriole density, and reduced iron accumulation compared with controls. Furthermore, echocardiology measurements showed hemin treatment induced significant improvements in left ventricular wall thickness, and cardiac function as indicated by increased ejection fraction, fractional shortening, and stroke volume measurements.ConclusionHemin has therapeutic potential to improve revascularisation and cardiac function in the heart post-MI.
NMR structure of the Orf63 pro-lytic protein from lambda bacteriophage
Authors: Khan Naushaba , Graham Tavawn , Franciszkiewicz Katarzyna , Bloch Sylwia , Nejman-Faleńczyk Bożena , Wegrzyn Alicja , Donaldson Logan W 
Published: October 2023

AbstractTheorf63gene resides in a region of the lambda bacteriophage genome between theexoandxisgenes and is among the earliest genes transcribed during infection. In lambda phage and Shiga toxin (Stx) producing phages found in enterohemorrhagicE. coli(EHEC) associated with food poisoning, Orf63 expression reduces the host survival and hastens the period between infection and lysis thereby giving it pro-lysogenic qualities. The NMR structure of dimeric Orf63 reveals a fold consisting of two helices and one strand that all make extensive intermolecular contacts. Structure-based data mining failed to identify any Orf63 homolog beyond the family of temperate bacteriophages. A machine learning approach was used to design an amphipathic helical ligand that bound a hydrophobic cleft on Orf63. This approach may open a new path towards designing therapeutics that antagonize the contributions of Stx phages in EHEC outbreaks.
Structure-guided mutagenesis of OSCAs reveals differential activation to mechanical stimuli
Authors: Jojoa-Cruz Sebastian , Dubin Adrienne E. , Lee Wen-Hsin , Ward Andrew 
Published: October 2023

AbstractThe dimeric two-pore OSCA/TMEM63 family has recently been identified as mechanically activated ion channels. Previously, based on the unique features of the structure of OSCA1.2, we postulated the potential involvement of several structural elements in sensing membrane tension1. Interestingly, while OSCA1, 2, and 3 clades are activated by membrane stretch in cell-attached patches (i.e., they are stretch-activated channels), they differ in their ability to transduce membrane deformation induced by a blunt probe (poking). In an effort to understand the domains contributing to mechanical signal transduction, we used cryo-electron microscopy to solve the structure ofArabidopsis thaliana(At) OSCA3.1, which, unlike AtOSCA1.2, only produced stretch- but not poke-activated currents in our initial characterization2. Mutagenesis and electrophysiological assessment of conserved and divergent putative mechanosensitive features of OSCA1.2 reveal a selective disruption of the macroscopic currents elicited by poking without considerable effects on stretch-activated currents (SAC). Our results support the involvement of the amphipathic helix and lipid-interacting residues in the membrane fenestration in the response to poking. Our findings position these two structural elements as potential sources of functional diversity within the family.
Separation of sticker-spacer energetics governs the coalescence of metastable condensates
Authors: Chattaraj Aniruddha , Shakhnovich Eugene I. 
Published: October 2023

AbstractBiological condensates often emerge as a multi-droplet state and never coalesce into one large droplet within the experimental timespan. Previous work revealed that the sticker-spacer architecture of biopolymers may dynamically stabilize the multi-droplet state. Here, we simulate the condensate coalescence using metadynamics approach and reveal two distinct physical mechanisms underlying the fusion of droplets. Condensates made of sticker-spacer polymers readily undergo a kinetic arrest when stickers exhibit slow exchange while fast exchanging stickers at similar levels of saturation allow merger to equilibrium states. On the other hand, condensates composed of homopolymers fuse readily until they reach a threshold density. Increase in entropy upon inter-condensate mixing of chains drives the fusion of sticker-spacer chains. We map the range of mechanisms of kinetic arrest from slow sticker exchange dynamics to density mediated in terms of energetic separation of stickers and spacers. Our predictions appear to be in qualitative agreement with recent experiments probing dynamic nature of protein-RNA condensates.Statement of significanceA key conundrum of biological condensates is the coexistence of multiple droplets, in direct variance with classical predictions of mean-field theories of polymer solutions. Our current study uncovers that the merging of sticker-spacer condensate is an entropy driven process, as opposed to the surface energy driven fusion that are observed for canonical liquid droplets. This entropy, stemming from the inter-condensate polymer exchange, makes the droplet merging process dependent on inter-sticker dissociation kinetics. Stronger inter-sticker interaction triggers a kinetic arrest, preventing the condensate merger even at a low density. Our prediction starkly correlates with recent experimental findings on protein-RNA condensates in vitro and in vivo, highlighting the biological relevance of the interplay of kinetics and thermodynamics.
Optimizing Phosphopeptide Structures That Target 14-3-3ε in Cutaneous Squamous Cell Carcinoma
Authors: Kamayirese Seraphine , Maity Sibaprasad , Dieckman Lynne M. , Hansen Laura A. , Lovas Sándor 
Published: October 2023

ABSTRACT14-3-3ε is involved in various types of malignancies by increasing cell proliferation, promoting cell invasion or inhibiting apoptosis. In cutaneous squamous cell carcinoma (cSCC), 14-3-3ε is over expressed and mislocalized from the nucleus to the cytoplasm where it interacts with the cell division cycle 25 A (CDC25A) and suppresses apoptosis. Hence inhibition of the 14-3-3ε - CDC25A interaction is an attractive target for promoting apoptosis in cSCC. In this work, we optimized the structure of our previously designed inhibitor of 14-3-3ε – CDC25A interaction, pT, a phosphopeptide fragment corresponding to one of the two binding regions of CDC25A to 14-3-3ε. Starting from pT, we developed peptide analogs that bind 14-3-3ε with nanomolar affinities. Peptide analogs were designed by shortening the pT peptide, and introducing modifications at position 510 of the pT(502-510) analog. Both molecular dynamics (MD) simulations and biophysical methods were used to determine peptides binding to 14-3-3ε. Shortening the pT peptide from 14 to 9 amino acid residues resulted in a peptide (pT(502-510)) that binds 14-3-3ε with a KDvalue of 45.2 nM. Gly to Phe substitution in position 510 of pT(502-510) led to further improvement in affinity (KD: 22.0 nM) of the peptide for 14-3-3ε. Our results suggest that the designed peptide analogs are potential candidates for inhibiting 14-3-3ε -CDC25A interactions in cSCC cells; thus, inducing their apoptosis.
ClonoScreen3D: a novel three-dimensional clonogenic screening platform for identification of radiosensitizers for glioblastoma
Authors: Jackson Mark R , Richards Amanda R , Oladipupo Abdul-Basit Ayoola , Chahal Sandeep K , Caragher Seamus , Chalmers Anthony J , Gomez-Roman Natividad 
Published: October 2023

AbstractPurposeGlioblastoma (GBM) is a lethal brain tumour. Standard of care treatment comprising surgery, radiation and chemotherapy results in median survival rates of 12-15 months. Molecular targeted agents identified using conventional two-dimensional (2D)in vitromodels of GBM have failed to improve outcome in patients, rendering such models inadequate for therapeutic target identification. We developed a 3D GBMin vitromodel that recapitulates key GBM clinical features and responses to molecular therapies and investigated its utility for screening novel radiation-drug combinations using gold-standard clonogenic survival as readout.ResultsPatient-derived GBM cell lines were optimized for inclusion in a 96-well plate 3D clonogenic screening platform, ClonoScreen3D. Radiation responses of GBM cells in this system were highly reproducible and comparable to those observed in low-throughout 3D assays. The screen methodology provided quantification of candidate drug single agent activity (EC50) and the interaction between drug and radiation (radiation interaction ratio, RIR). The PARP inhibitors talazoparib, rucaparib and olaparib, each showed a significant interaction with radiation by ClonoScreen3D and were subsequently confirmed as true radiosensitizers by full clonogenic assay. Screening a panel of DNA damage response inhibitors revealed the expected propensity of these compounds to interact significantly with radiation (13/15 compounds). A second screen assessed a panel of compounds targeting pathways identified by transcriptomic analysis and demonstrated single agent activity and a previously unreported interaction with radiation of dinaciclib and cytarabine (RIR 1.28 and 1.90, respectively). These compounds were validated as radiosensitizers in full clonogenic assays (sensitizer enhancement ratio 1.47 and 1.35, respectively).ConclusionsThe ClonoScreen3D platform was demonstrated to be a robust method to screen for single agent and radiation-drug combination activity. Using gold-standard clonogenicity, this assay is a tool for identification of novel radiosensitizers. We anticipate this technology will accelerate identification of novel radiation-drug combinations with genuine translational value.
Decolonising the NDIS: a third space to account for First Nations' values
Authors: Nikidehaghani Mona , Pupovac Sanja 
Published: October 2023

PurposeThis paper aims to investigate how embedding accounting techniques of cost and budgeting within the Australian National Disability Insurance Scheme (NDIS) potentially perpetuates colonial practices for Australian First Nations people living in remote areas. Further, the paper aims to explore how accounting might help to integrate the unique modes of accountability First Nations people have over disability care into the NDIS funding system. Ultimately, the aim is to discern whether accounting practices can be mobilised as a means to decolonising the NDIS framework.Design/methodology/approach This study uses a qualitative methodology to analyse public hearings from the Australian Disability Royal Commission. Drawing on Bhabha's (1994) concept of the “third space”, this study investigates how accounting techniques can be used to potentially decolonise the NDIS. This study also borrows Bhabha's (1994) concept of the third space to explore the potential for decolonising the NDIS through accounting techniques.FindingsFindings show that the accounting techniques pertaining to funding and costs embedded within the NDIS contribute to displacing and disconnecting First Nations people from their cultural practices and ways of life. Further, the analysis reveals that the NDIS funding system could help to decolonise the NDIS space if it were modified to incorporate First Nations' perspectives on accountability for disability care.Originality/valueThe case of the NDIS exposes glimpses of colonisation in contemporary Australia, where Western institutional and economic systems dominate over the structure and authority of the practice. In this paper, this study demonstrates that the accounting system used by the NDIS plays a role in marginalising First Nations people. However, accounting, as a technology of negotiation, could also be mobilised to enhance accountability for disability care outcomes and pave the way for decolonising public policies.
Navigating management control change: pathways to the future of work
Authors: Carr Michelle , Jooss Stefan 
Published: October 2023

PurposeCOVID-19 has forced Big 4 firms to challenge existing management control arrangements and adapt their ways of working. Yet, we know little about how management control might be enacted in the future of the sustainable workplace. The objective of the study is to examine the patterns of management control change in the Big 4 accounting firms during the COVID-19 pandemic.Design/methodology/approachAdopting an exploratory qualitative research design, the authors draw on 42 interviews with directors and associates in the Big 4 professional services firms.FindingsThe findings reveal two pathways of management control change including alignment and displacement. The authors found that relatively minor adaptions to action and result controls were relied upon to respond to substantial cultural and personnel control changes.Originality/valueThe contributions are threefold: the authors take a temporal perspective to (1) unpack the changes to management control arrangements; (2) theorise the findings by developing a three-dimensional taxonomy of change pathways encompassing pace, scope and longevity of management control change and (3) contextualise management control arrangements in a hybrid work setting.Highlights COVID-19 has forced Big 4 firms to challenge existing management control arrangements.Literature has focused on traditional, onsite work settings and largely ignored change pathways.The authors take a temporal perspective to unpack changes to management control arrangements.Big 4 firms adapted to hybrid work with substantial changes to personnel and cultural controls.The authors theorise the findings by developing a three-dimensional taxonomy of change pathways.
A comprehensive analysis for classification and regression of surface points based on geodesics and machine learning algorithms
Authors: Bulut Vahide 
Published: October 2023

PurposeFeature extraction from 3D datasets is a current problem. Machine learning is an important tool for classification of complex 3D datasets. Machine learning classification techniques are widely used in various fields, such as text classification, pattern recognition, medical disease analysis, etc. The aim of this study is to apply the most popular classification and regression methods to determine the best classification and regression method based on the geodesics.Design/methodology/approachThe feature vector is determined by the unit normal vector and the unit principal vector at each point of the 3D surface along with the point coordinates themselves. Moreover, different examples are compared according to the classification methods in terms of accuracy and the regression algorithms in terms of R-squared value.FindingsSeveral surface examples are analyzed for the feature vector using classification (31 methods) and regression (23 methods) machine learning algorithms. In addition, two ensemble methods XGBoost and LightGBM are used for classification and regression. Also, the scores for each surface example are compared.Originality/valueTo the best of the author’s knowledge, this is the first study to analyze datasets based on geodesics using machine learning algorithms for classification and regression.
Collaborative governance for aviation approved training organisation: an adapted model for multi-stakeholder collaboration
Authors: Hendra Oke , Kurnianto Benny , Endrawijaya Ika 
Published: October 2023

PurposeThis study aimed to develop an adapted collaborative governance model for aviation human resource development in Indonesia's approved training organisations (ATO), considering the expected changes in the industry due to advanced technologies. The model, based on Ansell and Gash's approach, emphasizes multi-stakeholder collaboration to ensure workforce development aligns with industry and regulatory standards and accommodates technological advancements.Design/methodology/approachQualitative methods, such as in-depth interviews and focus group discussions, were employed to collect and analyse data.FindingsThe results indicated that collaborative governance is a valuable tool for cultivating competent human resources and facilitating industry improvement in the face of rapid technological change.Originality/valueThe proposed model contributes significantly to the field by promoting inclusive and effective human resource development through the Centre for Aviation Human Resource Development (CAHRD), thereby preparing the Indonesian aviation industry for the impact of advanced technologies. Furthermore, this study contributes to the enhancement of Ansell and Gash's collaborative governance theoretical framework by effectively addressing its empirical gaps concerning vocational education and training challenges within Indonesia's air transportation sector.
A review on active heating for high performance cold-proof clothing
Authors: Ma Liang , Li Jun 
Published: October 2023

PurposeThe present study provides a comprehensive review of the advancements in five active heating modes for cold-proof clothing as of 2021. It aims to evaluate the current state of research for each heating mode and identify their limitations. Further, the study provides insights into the optimization of intelligent temperature control algorithms and design considerations for intelligent cold-proof clothing.Design/methodology/approachThis article presents a classification of active heating systems based on five different heating principles: electric heating system, solar heating system, phase-change material (PCM) heating system, chemical heating system and fluid/air heating system. The systems are analyzed and evaluated in terms of heating principle, research advancement, scientific challenges and application potential in the field of cold-proof clothing.FindingsThe rational utilization of active heating modes enhances the thermal efficiency of cold-proof clothing, resulting in enhanced cold-resistance and reduced volume and weight. Despite progress in the development of the five prevalent heating modes, particularly with regard to the improvement and advancement of heating materials, the current integration of heating systems with cold-proof clothing is limited to the torso and limbs, lacking consideration of the thermal physiological requirements of the human body. Additionally, the heating modes of each system tend to be uniform and lack differentiation to meet the varying cold protection needs of various body parts.Research limitations/implicationsThe effective application of multiple heating modes helps the human body to maintain a constant body temperature and thermal equilibrium in a cold environment. The research of heating mode is the basis for realizing the temperature control of cold-proof clothing and provides an effective guarantee for the future development of the intelligent algorithms for temperature control of non-uniform heating of body segments.Practical implicationsThe integration of multiple heating modes ensures the maintenance of a constant body temperature and thermal balance for the wearer in cold environments. The research of heating modes forms the foundation for the temperature regulation of cold-proof clothing and lays the groundwork for the development of intelligent algorithms for non-uniform heating control of different body segments.Originality/valueThe present article systematically reviews five active heating modes suitable for use in cold-proof clothing and offers guidance for the selection of heating systems in future smart cold-proof clothing. Furthermore, the findings of this research provide a basis for future research on non-uniform heating modes that are aligned with the thermal physiological needs of the human body, thus contributing to the development of cold-proof clothing that is better suited to meet the thermal needs of the human body.
Self-recovery after self-service technology failures: do motivations and self-efficacy matter?
Authors: Chiu Yen-Ting Helena , Nguyen Dung Minh , Hofer Katharina Maria 
Published: October 2023

PurposeThe growth of self-service technologies (SST) in the retail sector has led to an increased prevalence of SST failures, and spurred academic debate on customer self-recovery of the failed services. This study sets out to explore why customers prefer or decline to engage in self-recovery. A framework integrating elements from self-determination theory and theory of planned behavior is developed to explore the impact of motivational factors, attitudes and self-efficacy on self-recovery intention.Design/methodology/approachStructural equation modeling (SEM) was used to analyze the sample consisting of 297 users of retail kiosks in convenience stores.FindingsThe results revealed that intrinsic motivation and identified regulation directly affect customers' attitude and intention to engage in self-recovery. Despite an insignificant direct relationship, external regulation impacted self-recovery intention through attitude. Further, the association between intrinsic motivation and self-recovery intention is moderated by self-efficacy.Originality/valueMuch of the extant SST recovery literature has focused on company-rendered service recovery, providing little guidance to firms on how to promote self-recovery among customers. The integrated motivational-cognitive theoretical base in this study allows for a more differentiated inquiry into the factors shaping self-recovery intention, resulting in a deeper understanding of this topic. The novel insights will help retailers develop effective strategies for promoting self-recovery among users of retail kiosks.