bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modular evolution of secretion systems and virulence plasmids in a bacterial species complex
Authors: Chou Lin , Lin Yu-Chen , Haryono Mindia , Santos Mary Nia M. , Cho Shu-Ting , Weisberg Alexandra J. , Wu Chih-Feng , Chang Jeff H. , Lai Erh-Min , Kuo Chih-Horng 
Published: May 2021

AbstractBackgroundMany bacterial taxa are species complexes and uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilizedAgrobacterium tumefaciens, a taxon known for its phytopathogenicity and applications in transformation, as a study system and devised strategies for investigating genome diversity and evolution of species complexes.ResultsWe utilized 35 genome assemblies to achieve a comprehensive and balanced sampling ofA. tumefaciens. Our confident inference of gene content and core-genome phylogeny supported a quantitative guideline for delineating 12 species and allowed for robust investigations of genes critical in fitness and ecology. For the type VI secretion system (T6SS) involved in interbacterial competition and thought to be conserved, we detected multiple losses and one horizontal gene transfer. For the tumor-inducing plasmids (pTi) and pTi-encoded type IV secretion system (T4SS) that are essential for agrobacterial phytopathogenicity, we uncovered novel diversity and hypothesized their involvement in shaping this species complex. Intriguingly, for both T6SS and T4SS, genes encoding structural components are highly conserved, whereas extensive diversity exists for genes encoding effectors and other proteins.ConclusionsWe demonstrated that the combination of a phylogeny-guided sampling scheme and an emphasis on high-quality assemblies provides a cost-effective approach for robust analysis in evolutionary genomics. Our strategies for multi-level investigations at scales that range from whole-genomes to intragenic domains and phylogenetic depths of between- and within-species are applicable to other bacteria. Finally, modularity observed in the molecular evolution of genes and domains is useful for inferring functional constraints and informing experimental works.
A memristor-based neuromodulation device for real-time monitoring and adaptive control ofin vitroneuronal populations
Authors: Dias Catarina , Castro Domingos , Aroso Miguel , Ventura João , Aguiar Paulo 
Published: May 2021

AbstractNeurons are specialized cells in information transmission and information processing. Following this, many neurologic disorders are directly linked not to cellular viability/homeostasis issues but rather to specific anomalies in electrical activity dynamics. Acknowledging this fact, therapeutic strategies based on direct modulation of neuronal electrical activity have been producing remarkable results, with successful examples ranging from cochlear implants to deep brain stimulation. Development on these implantable devices are hindered, however, by important challenges: power requirements, size factor, signal transduction, and adaptability/computational capabilities. Memristors, nanoscale electronic components able to emulate natural synapses, provide unique properties to address these constraints and their use in neuroprosthetic devices is being actively explored. Here we demonstrate for the first time the use of memristive devices in a clinically relevant setting where communication between two neuronal populations is conditioned to specific activity patterns in the source population. In our approach, the memristor device performs a simple pattern detection computation and acts as a synapstor capable of reversible short-term plasticity. Usingin vitrohippocampal neuronal cultures, we show real-time adaptive control with a high degree of reproducibility using our monitor-compute-actuate paradigm. We envision very similar systems being used for automatic detection and suppression of seizures in epileptic patients.
The adenosine 2a receptor and TIM3 directly inhibit killing of tumor cells by cytotoxic T lymphocytes through interference with cytoskeletal polarization
Authors: Edmunds Grace L. , Wong Carissa C.W. , Ambler Rachel , Milodowski Emily , Alamir Hanin , Cross Stephen J. , Galea Gabriella , Wülfing Christoph , Morgan David J. 
Published: May 2021

AbstractTumors generate an immune-suppressive environment that prevents effective killing of tumor cells by CD8+ cytotoxic T cells (CTL). It remains largely unclear upon which cell type and at which stage of the anti-tumor response mediators of suppression act. We have combined an in vivo tumor model with a matching in vitro reconstruction of the tumor microenvironment based on tumor spheroids to identify suppressors of anti-tumor immunity that directly act on interaction between CTL and tumor cells and to determine mechanisms of action. An adenosine 2a receptor antagonist, as enhanced by blockade of TIM3, slowed tumor growth in vivo. Engagement of the adenosine 2a receptor and TIM3 reduced tumor cell killing in spheroids, impaired CTL cytoskeletal polarization ex vivo and in vitro and inhibited CTL infiltration into tumors and spheroids. With this focus on CTL killing, blocking A2aR and TIM3 complements therapies that enhance T cell priming, e.g. anti-PD1 and anti-CTLA-4.
Altered hippocampal transcriptome dynamics following sleep deprivation
Authors: Gaine Marie E. , Bahl Ethan , Chatterjee Snehajyoti , Michaelson Jacob. J. , Abel Ted , Lyons Lisa C. 
Published: May 2021

AbstractWidespread sleep deprivation is a continuing public health problem in the United States and worldwide affecting adolescents and adults. Acute sleep deprivation results in decrements in spatial memory and cognitive impairments. The hippocampus is vulnerable to acute sleep deprivation with changes in gene expression, cell signaling, and protein synthesis. Sleep deprivation also has long lasting effects on memory and performance that persist after recovery sleep, as seen in behavioral studies from invertebrates to humans. Although previous research has shown that acute sleep deprivation impacts gene expression, the extent to which sleep deprivation affects gene regulation remains unknown. Using an unbiased deep RNA sequencing approach, we investigated the effects of acute sleep deprivation on gene expression in the hippocampus. We identified 1,146 genes that were significantly dysregulated following sleep deprivation with 507 genes upregulated and 639 genes downregulated, including protein coding genes and long non-coding RNAs not previously identified as impacted by sleep deprivation. Notably, genes significantly upregulated after sleep deprivation were associated with RNA splicing and the nucleus. In contrast, downregulated genes were associated with cell adhesion, dendritic localization, the synapse, and postsynaptic membrane. These results clearly demonstrate that sleep deprivation differentially regulates gene expression on multiple transcriptomic levels to impact hippocampal function.Graphical Abstract
A novel gene-by-environment quantitative trait locus on mouse chromosome 15 underlies susceptibility to acute ozone-induced lung injury
Authors: Tovar Adelaide , Smith Gregory J. , Thomas Joseph M. , McFadden Kathryn M. , Kelada Samir N. P. 
Published: May 2021

AbstractRespiratory toxicity caused by the common urban air pollutant ozone (O3) varies considerably within the human population and across inbred mouse strains, suggestive of gene-environment interactions (GxE). Though previous studies genetic mapping studies using classical inbred strains have identified several and quantitative trait locus (QTL) and candidate genes underlying responses to O3 exposure, precise mechanisms of susceptibility remain incompletely described. We sought to expand our understanding of the genetic architecture of O3 responsiveness using the Collaborative Cross (CC) recombinant inbred mouse panel, which contains more genetic diversity than previous inbred strain panels. We evaluated hallmark O3-induced respiratory phenotypes in 56 CC strains after exposure to filtered air or 2 ppm O3, and performed focused genetic analysis of variation in lung injury as measured by the total bronchoalveolar lavage protein concentration. Because animals were exposed in sex- and batch-matched pairs, we defined a protein response phenotype as the difference in lavage protein between the O3- and FA-exposed animal within a pair. The protein response phenotype was heritable, and QTL mapping revealed two novel loci on Chromosomes 10 (peak: 26.2 Mb; 80% CI: 24.6-43.6 Mb) and 15 (peak: 47.1 Mb; 80% CI: 40.2-54.9 Mb), the latter surpassing the 95% significance threshold. At the Chr. 15 locus, C57BL/6J and CAST/EiJ founder haplotypes were associated with higher protein responses compared to all other CC founder strain haplotypes. Using additional statistical analysis and high-density SNP data, we delimited the Chr. 15 QTL to a ∼2 Mb region containing 21 genes (10 protein coding). Using a weight of evidence approach that incorporated candidate variant analysis, functional annotations, and publicly available lung gene expression data, we nominated three candidate genes (Oxr1, Rspo2, and Angpt1). In summary, we have shown that O3-induced lung injury is modulated by genetic variation and demonstrated the value of the CC for uncovering and dissecting gene-environment interactions.
Maladaptive avoidance learning in the orbitofrontal cortex in adolescents with major depression
Authors: Willinger David , Karipidis Iliana I. , Neuer Selina , Emery Sophie , Rauch Carolina , Häberling Isabelle , Berger Gregor , Walitza Susanne , Brem Silvia 
Published: May 2021

AbstractBackgroundUnderstanding the mechanisms in the brain’s incentive network that give rise to symptoms of major depressive disorder (MDD) during adolescence provides new perspectives to address MDD in early stages of development. This functional magnetic resonance imaging study determines whether instrumental vigor and brain responses to appetitive and aversive monetary incentives are altered in adolescent MDD and associated with symptom severity.MethodsAdolescents with moderate to severe MDD (n=30, age=16.1 [1.4]), and healthy controls (n=33, age=16.2 [1.9]) matched for age, sex, and IQ performed a monetary incentive delay task. During outcome presentation, prediction error signals were used to study the response and coupling of the incentive network during learning of cue-outcome associations. A computational reinforcement model was used to assess adaptation of response vigor. Brain responses and effective connectivity to model-derived prediction errors were assessed and related to depression severity and anhedonia levels.ResultsParticipants with MDD behaved according to a more simplistic learning model and exhibited slower learning. Effective connectivity analysis of fMRI data revealed that impaired loss error processing in the orbitofrontal cortex was associated with aberrant gain-control. Anhedonia scores correlated with loss-related error signals in the posterior insula and habenula.ConclusionsAdolescent MDD is selectively related to impaired processing of error signals during loss, but not reward, in the orbitofrontal cortex. Aberrant evaluation of loss outcomes might reflect an early mechanism of how negative bias and helplessness manifest in the brain. This approach sheds light on pathomechanisms in MDD and may improve early diagnosis and treatment selection.
Melanin Concentrating Hormone- and sleep-dependent synaptic downscaling is impaired in Alzheimer’s Disease
Authors: Calafate Sara , Özturan Gökhan , Thrupp Nicky , Vanderlinden Jeroen , Chen Wei-Ting , Fiers Mark , Lu Ashley , Creemers Eline , Craessaerts Katleen , Vandenbempt Joris , van Boekholdt Luuk , Poovathingal Suresh , Davie Kristofer , Thal Dietmar Rudolf , Wierda Keimpe , De Strooper Bart , de Wit Joris 
Published: May 2021

AbstractIn Alzheimer’s disease (AD), pathophysiological changes in the hippocampus cause deficits in episodic memory formation, leading to cognitive impairment 1,2. Neuronal hyperactivity is observed early in AD 3,4. Here, we find that homeostatic mechanisms transiently counteract increased neuronal activity in the hippocampal CA1 region of the AppNL-G-F humanized knock-in mouse model for AD 5, but ultimately fail to maintain neuronal activity at set-point. Spatial transcriptomic analysis in CA1 during the homeostatic response identifies the Melanin-Concentrating Hormone (MCH)-encoding gene. MCH is expressed in sleep-active lateral hypothalamic neurons that project to CA1 and modulate memory 6. We show that MCH regulates synaptic plasticity genes and synaptic downscaling in hippocampal neurons. Furthermore, MCH-neuron activity is impaired in AppNL-G-F mice, disrupting sleep-dependent homeostatic plasticity and stability of neuronal activity in CA1. Finally, we find perturbed MCH-axon morphology in CA1 early in AppNL-G-F mice and in AD patients. Our work identifies dysregulation of the MCH-system as a key player in aberrant neuronal activity in the early stages of AD.
Significance of Oct-4 transcription factor as a pivotal therapeutic target for CD44+/24- mammary tumour initiating cells; aiming at the root of the recurrence
Authors: Sen Utsav , Shanavas Shanooja , Gowda Apoorva , Nihad Muhammad , Rachamalla Hari Krishnareddy , Banerjee Rajkumar , Shenoy P Sudheer , Bose Bipasha 
Published: May 2021

AbstractBreast cancer (BC) remains one of the deadliest and frequently diagnosed metastatic cancers worldwide. Cancer stem cells (CSCs) are the cell population within the tumour niche, having an epithelial to mesenchymal (EMT) transition phenotype, high self-renewal, vigorous metastatic capacity, drug resistance, and tumour relapse. Identification of targets for induction of apoptosis is essential to provide novel therapeutic approaches in BC. Our earlier studies showed that Vitamin C induces apoptotic cell death by losing redox balance in TNBC CSCs. In this study, we have attempted to identify previously unrecognized CSC survival factors that can be used as druggable targets for bCSCs apoptosis regulators isolated from the TNBC line, MDA MB 468. After a thorough literature review, Oct-4 was identified as the most promising marker for its unique abundance in cancer and absence in normal cells and the contribution of Oct-4 to the sustenance of cancer cells. We then validated a very high expression of Oct-4 in the MDA MB 468 bCSCs population using flow-cytometry. The loss of Oct-4 was carried out using siRNA-mediated knockdown in the bCSCs, followed by assessing for cellular apoptosis. Our results indicated that Oct-4 knockdown induced cell death, changes in cellular morphology, inhibited mammosphere formation, and positive for Annexin-V expression, thereby indicating the role of Oct-4 in bCSC survival. Moreover, our findings also suggest the direct interaction between Oct-4 and Vitamin C using in silico docking. This data, hence, contributes towards novel information about Oct-4 highlighting this molecule as a novel survival factor in bCSCs.
The disruption of blockchain in auditing – a systematic literature review and an agenda for future research
Authors: Lombardi Rosa , de Villiers Charl , Moscariello Nicola , Pizzo Michele 
Published: May 2021

PurposeThis paper presents a systematic literature review, including content and bibliometric analyses, of the impact of blockchain technology (BT) in auditing, to identify trends, research areas and construct an agenda for future research.Design/methodology/approachThe authors include studies from 2010 to 2020 in their structured literature review (SLR), using accounting journals on the Scopus database, which yielded 40 articles with blockchain and auditing at its core.FindingsOne of the contributions of the authors’ analyses is to group the prior research, and therefore also the agenda for future research, into three main research areas: (1) Blockchain as a tool for auditing professionals to improve business information systems to save time and prevent fraud; (2) Smart contracts enabling Audit 4.0 efficiency, reporting, disclosure and transparency; (3) Cryptocurrency and initial coin offerings (ICOs) as a springboard for corporate governance and new venture financing. The authors’ findings have several important implications for practice and theory.Practical implicationsThe results of this study emphasise that (1) the disruption of blockchain in auditing is in a nascent phase and there is a need for compelling empirical studies and potential for the involvement of practitioners; (2) there may be a need to reconsider audit procedures especially suited for digitalisation and BT adoption; (3) standards, guidelines and training are required to pivot towards and confront the challenge BT will represent for auditing; and (4) there are two sides to the BT coin for auditing, enthusiasm about the potential and risk upon implementation. These practical implications can also be seen as a template for future research in a quest to align theory and practice.Originality/valueThe authors’ SLR facilitates the identification of research areas and implications, forming a useful baseline for practitioners, professionals and academics, as they draft the state of the art on the disruption of blockchain in auditing, highlighting how BT is changing auditing activities and traditions.
Agency costs, board structure and institutional investors: case of India
Authors: Chaudhary Pankaj 
Published: May 2021

PurposeThe author examines the role of board structure and institutional investors in dealing with the agency issues for the Indian firms by taking the data of NSE-500 nonfinancial firms for the period 2010–2019.Design/methodology/approachThe author applies dynamic panel data methodology to deal with endogeneity concerns prevalent in corporate finance variables.FindingsThe agency view is consistent with the board size in the context of India. The author observed that the board size has a harmful effect on agency cost. A larger board size may create a coordination problem, or CEO may find it easy to thrust his or her decisions on board. The author also noticed that firms should have sizeable institutional ownership, particularly pressure-insensitive investors, in equity as they can reduce agency-related issues.Originality/valueThis study focuses on one of the largest emerging economies, i.e. India.
Does a healthy diet travel? Motivations, satisfaction and loyalty with plant-based food dining at destinations
Authors: Chang Janet , Morrison Alastair M. , Chen Ya-Ling , Chang Te-Yi , Chen Daniela Zih-Yu 
Published: May 2021

PurposeThe research objectives were to: (1) examine the relationship among motivations, satisfaction and loyalty with plant-based food dining at destinations; (2) determine if and how the attractiveness of eating plant-based foods moderates satisfaction and loyalty; and (3) investigate potential differences in visitor background information and consumption characteristics.Design/methodology/approachA survey was conducted at tourist attractions in southern Taiwan and 274 valid questionnaires were obtained. The relationships among motivations, satisfaction and loyalty were investigated when eating plant-based foods during travel. The moderating effects of food attractiveness on motivations and satisfaction/loyalty were measured.FindingsThe results indicated a positive relationship between motivations and satisfaction/loyalty in plant-based food dining. Motivations for plant-based food dining were comprised of four domains (physical, cultural, interpersonal and prestige) and satisfaction and loyalty had three (overall satisfaction, intention to revisit and intention to recommend).Research limitations/implicationsThe major implications were that motivations had a significant effect on satisfaction and loyalty; food attractiveness did not moderate the effect of motivations on satisfaction/loyalty; and background characteristics influenced satisfaction and loyalty.Practical implicationsMarketers and strategic planners for plant-based restaurants or those with plant-based meal options must make a greater effort to understand the distinctive demographic and dietary characteristics of the people who comprise the core of this market.Originality/valueThis research adds to the very limited literature on plant-based and vegetarian dining in tourism destinations. Furthermore, it tests, partially validates and expands a model by Kim et al. (2009) for consuming local food while traveling. The findings also complement the considerable evidence linking motivations to satisfaction and loyalty when dining.
Grape residue flour as an antioxidant and fiber source in beef meatballs
Authors: Tuffi Larissa Christine , Longhi Daniel Angelo , Hernandes Jéssica Carvalho , Gregório Paulo Cézar , Rocha Garcia Carlos Eduardo 
Published: May 2021

PurposeThis study aimed at the addition of grape residue flours in beef meatballs to evaluate their behavior on physic-chemical and sensory properties. Furthermore, it is intended to discuss the importance of the substitution of synthetic additives with natural ones, the enhancement of consumers' diets and the prevention of inappropriate waste disposal.Design/methodology/approachThe grapes' residues were collected from wine production and transformed into flour. Their proximal chemical composition and antioxidant activities were analyzed. Then, meatballs were formulated with 0 (control), 3.5 and 7% grape flours. Lipid oxidation analyzes were performed on raw and thermally processed meatballs. Triangle and ranking sensory tests were performed to assess the consumer's perception of product appearance and flavor and the consumer's preference, respectively.FindingsBordeaux and Trebbiano grape flours were rich in dietary fibers, composed of 44.2 and 55.6% fibers, respectively. They showed a high antioxidant activity, in which Trebbiano was high than Bordeaux. The addition of grape flours reduced the lipid oxidation of meatballs by close to 50% than the control sample. Differences in the appearance and flavor of some meatballs were identified by the panelists; however, the flavor's change did not displease them.Originality/valueThe grape residue is rich in phenolic compounds, natural dyes and dietary fibers. Its addition as a functional ingredient in meatballs reduces the addition of synthetic additives, adds fiber to the consumer's diet and prevents inappropriate waste disposal.
Induction machine stator short-circuit fault detection using support vector machine
Authors: Bensaoucha Saddam , Brik Youcef , Moreau Sandrine , Bessedik Sid Ahmed , Ameur Aissa 
Published: May 2021

Purpose
This paper provides an effective study to detect and locate the inter-turn short-circuit faults (ITSC) in a three-phase induction motor (IM) using the support vector machine (SVM). The characteristics extracted from the analysis of the phase shifts between the stator currents and their corresponding voltages are used as inputs to train the SVM. The latter automatically decides on the IM state, either a healthy motor or a short-circuit fault on one of its three phases.

Design/methodology/approach
To evaluate the performance of the SVM, three supervised algorithms of machine learning, namely, multi-layer perceptron neural networks (MLPNNs), radial basis function neural networks (RBFNNs) and extreme learning machine (ELM) are used along with the SVM in this study. Thus, all classifiers (SVM, MLPNN, RBFNN and ELM) are tested and the results are compared with the same data set.

Findings
The obtained results showed that the SVM outperforms MLPNN, RBFNNs and ELM to diagnose the health status of the IM. Especially, this technique (SVM) provides an excellent performance because it is able to detect a fault of two short-circuited turns (early detection) when the IM is operating under a low load.

Originality/value
The original of this work is to use the SVM algorithm based on the phase shift between the stator currents and their voltages as inputs to detect and locate the ITSC fault.