bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic analysis revealed that the oomyceticide phosphite exhibits multi-modal action in an oomycete pathosystem
Authors: Andronis Christina E. , Jacques Silke , Lopez-Ruiz Francisco J. , Lipscombe Richard , Tan Kar-Chun 
Published: August 2022

ABSTRACTBACKGROUNDPhytopathogenic oomycetes constitute some of the most devastating plant pathogens that cause significant crop and horticultural loss. Phytophthora cinnamomi is a phytopathogenic oomycete that causes dieback disease in native vegetation and a variety of crops. This pathogen can survive through harsh environmental conditions which gives it an advantage over its susceptible hosts. The only implemented chemical used to control P. cinnamomi is the oomyceticide phosphite. Despite its widespread use, the mode of action of phosphite is not well understood and it is unclear whether it works directly on the pathogen or through the host. Additionally, resistance to phosphite is emerging in P. cinnamomi isolates and other oomycete phytopathogens.RESULTSThe mode of action of phosphite on the pathogen and through a model host was investigated using label-free quantitative proteomics. In vitro treatment of P. cinnamomi with phosphite hinders growth by interfering with metabolism, signalling and gene expression, traits that are not observed in the tolerant isolate. When the model host L. angustifolius was treated with phosphite, enrichment of proteins that are associated with photosynthesis, carbon fixation and lipid metabolism in the host was observed. An increase in the production of a range of defence-related proteins was observed.CONCLUSIONWe hypothesise direct and indirect models of the multi-modal action of phosphite that directly targets the pathogen as well as alters plant metabolism and immune response.
Hierarchical processing underpins competition in tactile perceptual bistability
Authors: Darki Farzaneh , Ferrario Andrea , Rankin James 
Published: August 2022

AbstractAmbiguous sensory information can lead to spontaneous alternations between perceptual states, recently shown to extend to tactile perception. The authors recently proposed a simplified form of tactile rivalry which evokes two competing percepts for a fixed difference in input amplitudes across antiphase, pulsatile stimulation of the left and right fingers. This study addresses the need for a tactile rivalry model that captures the dynamics of perceptual alternations and that incorporates the structure of the somatosensory system. The model features hierarchical processing with two stages; a first stage resolves perceptual competition, leading to perceptual alternations; and a second stage encodes perceptual interpretations. The first stage could be located downstream of brainstem nuclei and the second stage could be located within the primary somatosensory cortex (area 3b). The model captures dynamical features specific to the tactile rivalry percepts and produces general characteristics of perceptual rivalry: input strength dependence of dominance times (Levelt’s proposition II), short-tailed skewness of dominance time distributions and the ratio of distribution moments. The presented modelling work leads to experimentally testable predictions. The same hierarchical model could generalise to account for percept formation, competition and alternations for bistable stimuli that involve pulsatile inputs from the visual and auditory domains.Author summaryPerceptual ambiguity involving the touch sensation has seen increased recent interest. It provides interesting opportunity to explore how our perceptual experience is resolved by dynamic computations in the brain. We recently proposed a simple form of tactile rivalry where stimuli consisted of antiphase sequences of high and low intensity pulses delivered to the right and left index fingers. The stimulus can be perceived as either one simultaneous pattern of vibration on both hands, or as a pattern of vibrations that jumps from one hand to the other, giving a sensation of apparent movement. During long presentation of the stimuli, one’s perception switches every 5–20 seconds between these two interpretations, a phenomenon called tactile perceptual bistability. This study presents the first computational model for tactile bistability and is based on the structure of sensory brain areas. The model captures important characteristics of perceptual interpretations for tactile rivalry. We offer predictions in terms of how left-right tactile intensity differences are encoded and propose a location for the encoding of perceptual interpretations in sensory brain areas. The model provides a generalisable framework that can make useful predictions for future behavioural experiments with tactile and other types of stimuli.
Exploring therapeutic strategies for Infantile Neuronal Axonal Dystrophy (INAD/PARK14)
Authors: Lin Guang , Tepe Burak , McGrane Geoff , Tipon Regine C. , Croft Gist , Panwala Leena , Hope Amanda , Liang Agnes J.H. , Zuo Zongyuan , Wang Lily , Bellen Hugo J. 
Published: August 2022

AbstractInfantile Neuroaxonal Dystrophy (INAD) is caused by recessive variants in PLA2G6 and is a lethal pediatric neurodegenerative disorder. Loss of the Drosophila homolog of PLA2G6, leads to ceramide accumulation, lysosome expansion, and mitochondrial defects. Here, we report that ceramide metabolism, the endolysosomal pathway, and mitochondrial morphology are affected in INAD patient-derived neurons. We show that in INAD mouse models the same features are affected and that glucosylceramides are elevated in dopaminergic neurons and Purkinje cells, arguing that the neuropathological mechanisms are evolutionary conserved and that ceramides can be used as biomarkers. We tested 20 drugs that target these pathways and found that Ambroxol, Desipramine, Azoramide, and Genistein alleviate neurodegenerative phenotypes in INAD flies and INAD patient-derived NPCs. We also develop an AAV-based gene therapy approach that delays neurodegeneration and prolongs lifespan in an INAD mouse model.One Sentence SummaryCeramide accumulation, lysosomal expansion and mitochondrial defects are a root cause of INAD/PARK14.
ENGRAILED-1 transcription factor has a paracrine neurotrophic activity on adult spinal α-motoneurons
Authors: Lebœuf Mélanie , Vargas-Abonce Stephanie E. , Pezé-Hedsieck Eugénie , Dupont Edmond , Jimenez-Alonso Lucia , Moya Kenneth L. , Prochiantz Alain 
Published: August 2022

ABSTRACTSeveral homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, and chromatin organization in recipient cells. ENGRAILED-1 is one such homeoprotein expressed in spinal V1 interneurons synapsing on α-motoneurons. Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in α-motoneurons loss and limb weakness. A similar but stronger phenotype is observed in theEngrailed-1heterozygote mouse, confirming that ENGRAILED-1 exerts a paracrine neurotrophic activity on spinal cord α-motoneurons. Intrathecal injection of ENGRAILED-1 leads to its specific internalization by spinal motoneurons and has long-lasting protective effects against neurodegeneration and weakness. Midbrain dopaminergic neurons expressEngrailed-1and, similarly to spinal cord α-motoneurons, degenerate in the heterozygote. By identifying genes expressed in spinal cord motoneurons also showing modified expression in mouseEngrailed-1heterozygote midbrain neurons, we identified p62/SQTSM1 as an age marker in spinal cord motoneurons with increased expression during aging, in theEngrailed-1heterozygote and upon extracellular ENGRAILED-1 neutralization. We conclude that ENGRAILED-1 is a regulator of motoneuron ageing with non-cell autonomous neurotrophic activity.
Using Machine Learning to identify microRNA biomarkers for predisposition to Huntington’s Disease
Authors: Patel K , Sheridan C , Shanley DP 
Published: August 2022

AbstractBackgroundHuntington’s disease (HD) is an autosomal dominant disease which is triggered by a large expansion of CAG nucleotides in theHTTgene. While the CAG expansion linearly correlates with the age of disease onset in HD, twin-studies and cohorts of Juvenile Onset HD (JOHD) patients have shown other factors influence the progression of HD. Thus, it would be of interest to identify molecular biomarkers which indicate predisposition to the development of HD, and as microRNAs (miRNAs) circulate in bio-fluids they would be particularly useful biomarkers. We explored a large HD miRNA-mRNA expression dataset (GSE65776) to establish appropriate questions that could be addressed using Machine Learning (ML). We sought sets of features (mRNAs or miRNAs) to predict HD or WT samples from aged or young mouse cortex samples, and we asked if a set of features could predict predisposition to HD or WT genotypes by training models on aged samples and testing the models on young samples. Several models were created using ADAboost, ExtraTrees, GaussianNB and Random Forest, and the best performing models were further analysed using AUC curves and PCA plots. Finally, genes used to train our miRNA-based predisposition model were mined from HD patient bio-fluid samples.ResultsOur testing accuracies were between 66-100% and AUC scores were between 31-100%. We generated several excellent models with testing accuracies >80% and AUC scores >90%. We also identified homologues ofmmu-miR-154-5p,mmu-miR-181a-5p,mmu-miR-212-3p, mmu-miR-378b, mmu-miR-382-5pandmmu-miR-770-5pfrom our miRNA-based predisposition model to be circulating in HD patient blood samples at p.values of <0.05.ConclusionsWe generated several age-based models which could differentiate between HD and WT samples, including an aged mRNA-based model with a 100% AUC score, an aged miRNA-based model with a 92% AUC score and an aged miRNA-based model with a 96% AUC score. We also identified several miRNAs used to train our miRNA-based predisposition model which were detectable in HD patient blood samples, which suggests they could be potential candidates for use as non-invasive biomarkers for HD research.
Plasma membrane nanodeformations promote actin polymerisation through CIP4/CDC42 recruitment and regulate type II IFN signaling
Authors: Benjamin Ledoux , Natacha Zanin , Jinsung Yang , Charlotte Coster , Christine Dupont-Gillain , David Alsteens , Pierre Morsomme , Henri-François Renard 
Published: August 2022

AbstractIn their environment, cells have to cope with mechanical stresses constantly. Among those, nanoscale deformations of plasma membrane induced by substrate nanotopography are now largely accepted as a biophysical stimulus influencing cell behaviour and function. However, the mechanotransduction cascades involved and their precise molecular effects on cellular physiology are still poorly understood. Here, using homemade fluorescent nanostructured cell culture surfaces, we explored the role ofBin/Amphiphysin/Rvs (BAR) domain proteins as mechanosensors of plasma membrane geometry. Our data reveal that distinct subsets of BAR proteins bind to plasma membrane deformations in a membrane curvature radius-dependent manner. Furthermore, we show that membrane curvature promotes the formation of dynamic actin structures mediated by the Rho GTPase CDC42, the F-BAR protein CIP4 and the presence of PI(4,5)P2, independently of clathrin. In addition, these actin-enriched nanodomains can serve as platforms to regulate receptor signaling as they appear to contain Interferon γreceptor (IFNγ-R) and to lead to the partial inhibition of IFNγ-induced Janus-activated tyrosinekinase/signal transducer andactivator of transcription (JAK/STAT) signaling.
Evolution of quality assurance practices in enhancing the quality of open and distance education in a developing nation: a case study
Authors: Ferdousi Farhana , Ahmed Amir , Momen Md Abdul 
Published: August 2022

PurposeThe purpose of this study is to look at the challenges and successes that the case institution has had in implementing and maintaining quality assurance (QA) processes. The study also looks into the role of QA techniques in improving an institution's performance in a developing country.Design/methodology/approachThe research is qualitative. Nine significant persons were interviewed, including the institution's top administration, faculty members and related staff. Data were gathered to learn more about the background, incremental changes and numerous internal and external elements that influenced how QA was approached over time.FindingsThe findings revealed the challenges and experiences of the evolution of QA practices in the case institution. The results show the changes in QA practices regarding three aspects, including people, place and program of case institutions under three phases. During phases I and II, the adoption and upgradation of QA practices were very slow; phase III showed significant improvement in all three aspects. In addition, the positive impact of QA practices is evident in improving the performance of students and teaching and nonteaching staff of the case institution.Practical implicationsThe findings of this research could aid open and distance learning (ODL) providers in other developing nations in understanding the challenges of such a system. It may also make it easier for other ODL providers to comprehend the QA-led success in stakeholder confidence, employability and reputation.Originality/valueThe research will give insights into how QA procedures are used and valued in ODL in developing nations.
Community-led guerrilla drug checking in response to deaths from adulterated MDMA in Victoria, Australia
Authors: Barratt Monica J. , Bright Stephen J. , Blackwell Ash R. 
Published: August 2022

Purpose
Following deaths and hospitalisations in Melbourne, Victoria, Australia, related to the unwitting consumption of a combination of 25C-NBOMe and 4-FA, a community-led unauthorised drug checking service was rapidly established at a subsequent music festival. We aim to demonstrate the value of community-led drug checking, even when conducted in less-than-ideal conditions, by describing this service and reporting on its outcomes.

Design/methodology/approach
In all, 131 samples were tested with between 1 and 4 (M = 2.24 and SD = 0.61) reagents (Mandelin, Marquis, Mecke and Simons), and behavioural intentions of service users were reported.

Findings
People whose results indicated that the drug tested was what they expected, or was a drug familiar to them, were more likely to report an intention to take the drug compared to those whose results indicated that the drug was not what they had expected. For example, in 11 cases where the expected substance was not identified and novel substances including 2 C-X (including the NBOMe series), methylone, mephedrone, PMA and MXE were indicated, most reported an intention to discard (8/11).

Practical implications
The guerrilla service appeared to dissuade some people from consuming substances with higher risk profiles. It was also quick to identify substances of concern consistent with the NBOMe/4-FA combination for broader community action. The authors urge governments in Australia and elsewhere to reconsider their opposition to drug checking services, given their utility as vital health services during times of volatile drug market shifts.

Originality/value
While these data are five years old, it has only been in the past year that the Coroners Court of Victoria finalised their report on the deaths associated with this drug outbreak, providing context for the rapid peer response.
BIM implementation: an empirical validation for a four-wheel model
Authors: Olugboyega Oluseye , Windapo Abimbola , Aigbavboa Clinton , Oseghale Godwin Ehis 
Published: August 2022

PurposeBecause BIM adoption is still afflicted by various types of hurdles, a complete BIM implementation model is required to provide the necessary methods for driving BIM adoption. As a result, this study looked into the parts of the BIM implementation model that had the most impact on increasing the percentage of BIM adoption in South Africa.Design/methodology/approachThis study developed a four-wheel model of BIM implementation based on implementation process theory, which includes BIM inspiration, BIM capacity development, BIM use and BIM commitment. To assess BIM capacity development, two sub-constructs (BIM learning process and BIM learning methodologies) were used. Two sub-constructs were used to assess BIM utilisation (efficient BIM application and effective BIM application). The sub-constructs employed to quantify BIM motivation were organisational competitiveness, societal conformity and contractual obligations. Incentives, investments and obligations were used to assess BIM commitment. The model was validated using four assumptions and maximum likelihood estimation – structural equation modelling (MLE-SEM).FindingsThe MLE-SEM results demonstrated unequivocally that all of the constructions are critical components of the BIM deployment paradigm in the South African construction industry. BIM motivation, as characterised by organisational competitiveness and social compliance, has the greatest impact. The findings on BIM motivation also revealed that the desire for technological sophistication, competitiveness and social acceptance by clients are encouraging construction organisations and professionals to embrace BIM adoption.Research limitations/implicationsThis study's findings have contributed to the increasing body of literature on BIM deployment. The study has significant implications for achieving BIM implementation in underdeveloped nations where BIM deployment is either non-existent or in its early stages. The theoretical component of the study serves as the foundation for further analysis of BIM deployment.Practical implicationsThis research is important for identifying BIM goals, developing a BIM implementation framework, allocating resources for BIM implementation and defining key performance indicators for BIM implementation. The BIM implementation aspects outlined in this study will be effective in lowering BIM adoption hurdles.Originality/valueThis study makes a unique contribution to BIM research by providing theoretical and empirical analysis into the elements of the BIM implementation model in a developing country. The study offers an excellent opportunity to further our understanding of BIM application in underdeveloped nations.
Pandemic transitions: impact on business school campus recruitments
Authors: Gupta Anupama , Haldar Arunima , Srivastava Sushmita 
Published: August 2022

Purpose
This study aims to examine the transitions in hiring criteria by recruiting companies in top ten Quacquarelli Symonds ranked business schools in India during the pandemic.

Design/methodology/approach
Using an exploratory lens, an in-depth semistructured interview was conducted with 20 recruiting companies across industries and roles.

Findings
Content analysis suggests the changing preferences in hiring criteria and identifies six themes that have assumed importance during the pandemic period.

Research limitations/implications
This study has implications for business school participants who need to change their preparation strategy during the placement season.

Practical implications
There is an opportunity for business schools to focus on these two soft skills, namely, self-management with self-discipline and oral and written communication across the platform. However, in the depth and diversity of soft skills training, there is often a shallow coverage of multiple skills. The rather focused approach to developing these two skills may go a long way in preparing work-delivery graduates who could hit the proverbial ground running as the first step into their careers.

Originality/value
This study contributes to hiring managers by suggesting the traits that may assume importance in the new normal where remote or hybrid working context is a necessity.
Configuring problems of economics in Islamic perspective: moral nexus, realities and its unification
Authors: Furqani Hafas , Haneef Mohamed Aslam 
Published: August 2022

Purpose
This paper aims to investigate the subject matter of Islamic economics that will be the object of a study as a discipline by classifying and unifying different approaches proposed by Islamic economists.

Design/methodology/approach
The paper is a conceptual paper using discursive analysis analysing the perspective and approaches proposed by Islamic economists in defining economic problems from an Islamic perspective. The perspective and approaches proposed are classified and analysed for their implications in constructing the subject matter of discipline.

Findings
Islamic economics, as a new body of knowledge, needs to clarify the economic problems that will be its subject matter. The paper brings an insight into the subject matter of Islamic economics as conceived by scholars in two approaches, namely, economic problems “as they are” and economic problems “as they should be”. The paper also proposes a unified perspective in defining the subject matter of Islamic economics for further development of the discipline.

Research limitations/implications
This paper only provides philosophical guidance for researchers in mapping the problems and the goals of the policy being studied, although it does not offer any practical use for policymaking as each policy is faced with different and specific cases. This paper may be used to assist future researchers in shaping other unexplored fields in Islamic economics as a body of knowledge.

Practical implications
Islamic economics as a discipline will be strengthened if it has a clear subject matter that will be the object of study. However, the conception of economic problems proposed by Islamic economists is based on life-reality, i.e. of what human beings face in their life (practical-type economic problems as they are) and based on life guidance from the Qur’an on how human beings should live as well as life-objectives, i.e. of what goals he should strive for (ideal-type economic problems as they ought to be) brings implication that there are differences in determining the object of study of Islamic economics.

Originality/value
This paper promotes the unification of two conceptions of economic problems proposed by scholars by defining Islamic economics as “a study of resource appropriation to realize human well-being (maslahah)”. This suggests that economic problems as manifested in life reality will be studied within the grand objective of life in Islam (maqasid al-Shariah), and economic problems as perceived in life goals will be studied in the context of life reality. Islamic economic theory will be formulated not only to solve the apparent problem of “what is” but also formulated in a way that refers to goals (ideals) of “what ought to be” that will provide solutions to current economic problems according to certain vision and to take steps to move in that visionary direction.