bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex synaptic and intrinsic interactions disrupt input/output functions in the hippocampus ofScn1bknockout mice
Authors: Chancey Jessica Hotard , Ahmed Alisha A. , Guillén Fernando Isaac , Howard MacKenzie A. 
Published: April 2023

AbstractMutations in theSCN1Bgene have been linked to severe developmental epileptic encephalopathies including Dravet syndrome.Scn1bknockout (KO) mice modelSCN1Bloss of function disorders, demonstrating seizures, developmental delays, and early death.SCN1Bencodes the protein β1, an ion channel auxiliary subunit that also has roles in cell adhesion, neurite outgrowth, and gene expression. The goal of this project is to better understand of how loss of β1 alters information processing in the brain, resulting in seizures and associated cognitive dysfunction. Using slice electrophysiology in the CA1 region of the hippocampus from male and femaleScn1bKO mice andwild-type (WT) littermates, we found that processing of physiologically relevant patternedSchaffercollateral (SC) stimulation produces larger, prolonged depolarizations and increased spiking in KO neurons compared to WTs. KO neurons exhibit enhanced intrinsic excitability, firing more action potentials with current injection. Interestingly, SC stimulation produces smaller, more facilitating excitatory and inhibitory postsynaptic currents in KO pyramidal neurons, but larger postsynaptic potentials with the same stimulation. We also found reduced intrinsic firing of parvalbumin-expressing interneurons and disrupted recruitment of both parvalbumin- and somatostatin-expressing interneurons in response to patterned synaptic stimulation. Neuronal information processing relies on the interplay between synaptic properties, intrinsic properties that amplify or suppress incoming synaptic signals, and firing properties that produce cellular output. We found changes at each of these levels inScn1bKO pyramidal neurons, resulting in fundamentally altered information processing in the hippocampus that likely contributes to the complex phenotypes ofSCN1B-linked epileptic encephalopathies.Significance statementGenetic developmental epileptic encephalopathies have limited treatment options, in part due to our lack of understanding of how genetic changes result in dysfunction at the cellular and circuit levels.SCN1Bis a gene linked to Dravet syndrome and other epileptic encephalopathies, andScn1bknockout mice phenocopy the human disease, allowing us to study underlying neurophysiological changes. Here we found changes at all levels of neuronal information processing in brains lacking β1, including intrinsic excitability, synaptic properties, and synaptic integration, resulting in greatly enhanced input/output functions of the hippocampus. Our study shows that loss of β1 results in a complex array of cellular and network changes that fundamentally alters information processing in the hippocampus.
Descending GABAergic Neurons of the RVM That Mediate Widespread Bilateral Antinociception
Authors: Ganley Robert P. , Magalhaes de Sousa Marília , Ranucci Matteo , Werder Kira , Öztürk Tugce , Wildner Hendrik , Zeilhofer Hanns Ulrich 
Published: April 2023

SummaryNeurons projecting from the rostral ventromedial medulla (RVM) to the spinal dorsal horn are critical elements of endogenous pain control systems. Here, we describe a GABA/glycinergic pathway that predominantly innervates the superficial dorsal horn. Anatomical and optogenetic tracing of these neurons from a single unilateral site of the lumbar spinal cord indicated that these neurons give rise to a dense bilateral innervation of the spinal cord along its entire rostrocaudal axis. Chemogenetic activation of these neurons caused a bilateral and widespread reduction in heat, cold, and mechanical sensitivity, while their silencing with tetanus toxin induced allodynia and spontaneous pain-like aversive behaviors. Consistent with a continuous role in the prevention of spontaneous pain, many descending RVM GABAergic neurons were found to be tonically active. This pathway may therefore be relevant for widespread conditioned analgesia, while its dysfunction may underlie chronic widespread pain syndromes.
Localization and Quantification of Post-Translational Modifications of Proteins Using Electron Activated Dissociation Fragmentation on a Fast-Acquisition Time-of-Flight Mass Spectrometer
Authors: Bons Joanna , Hunter Christie L. , Chupalov Rita , Causon Jason , Antonoplis Alexandra , Rose Jacob P. , MacLean Brendan , Schilling Birgit 
Published: April 2023

ABSTRACTProtein post-translational modifications (PTMs) are crucial and dynamic players in a large variety of cellular processes and signaling, and proteomic technologies have emerged as the method of choice to profile PTMs. However, these analyses remain challenging due to potential low PTM stoichiometry, the presence of multiple PTMs per proteolytic peptide, PTM site localization of isobaric peptides, and labile PTM groups that lead to neutral losses. Collision-induced dissociation (CID) is commonly used for to characterize PTMs, but the application of collision energy can lead to neutral losses and incomplete peptide sequencing for labile PTM groups. In this study, we compared CID to an alternative fragmentation, electron activated dissociation (EAD), operated on a recently introduced fast-acquisition quadrupole-time-of-flight (QqTOF) mass spectrometer. We analyzed a series of synthetic modified peptides, featuring phosphorylated, succinylated, malonylated, and acetylated peptides. We performed targeted, quantitative parallel reaction monitoring (PRM or MRMHR) assays to assess the performances of EAD to characterize, site-localize and quantify peptides with labile modifications. The tunable EAD kinetic energy allowed the preservation of labile modifications and provided better peptide sequence coverage with strong PTM-site localization fragment ions. Zeno trap activation provided significant MS/MS sensitivity gains by an average of 6–11-fold for EAD analyses, regardless of modification type. Evaluation of the quantitative EAD PRM workflows revealed high reproducibility with coefficients of variation of typically ∼2%, as well as very good linearity and quantification accuracy. This novel workflow, combining EAD and Zeno trap, offers confident, accurate, and robust characterization and quantification of PTMs.
Fight not flight: parasites drive the bacterial evolution of resistance, not escape
Authors: Blazanin Michael , Moore Jeremy , Olsen Sydney , Travisano Michael 
Published: April 2023

AbstractIn the face of ubiquitous threats from parasites, hosts can evolve strategies to resist infection or to altogether avoid parasitism, for instance by avoiding behavior that could expose them to parasites or by dispersing away from local parasite threats. At the microbial scale, bacteria frequently encounter viral parasites, bacteriophages. While bacteria are known to utilize a number of strategies to resist infection by phages, and can have the capacity to avoid moving towards phage-infected cells, it is unknown whether bacteria can evolve dispersal to escape from phages. In order to answer this question, we combined experimental evolution and mathematical modeling. Experimental evolution of the bacteriumPseudomonas fluorescensin environments with differing spatial distributions of the phage Phi2 revealed that the host bacteria evolved resistance depending on parasite distribution, but did not evolve dispersal to escape parasite infection. Simulations using parameterized mathematical models of bacterial growth and swimming motility showed that this is a general finding: while increased dispersal is adaptive in the absence of parasites, in the presence of parasites that fitness benefit disappears and resistance becomes adaptive, regardless of the spatial distribution of parasites. Together, these experiments suggest that parasites should rarely, if ever, drive the evolution of bacterial escape via dispersal.
Unsupervised segmentation of 3D microvascular photoacoustic images using deep generative learning
Authors: Sweeney Paul W. , Hacker Lina , Lefebvre Thierry L. , Brown Emma L. , Gröhl Janek , Bohndiek Sarah E. 
Published: April 2023

AbstractMesoscopic photoacoustic imaging (PAI) enables label-free visualisation of vascular networks in tissue at high contrast and resolution. The segmentation of vascular networks from 3D PAI data and interpretation of their meaning in the context of physiological and pathological processes is a crucial but time consuming and error-prone task. Deep learning holds potential to solve these problems, but current supervised analysis frameworks require human-annotated ground-truth labels. Here, we overcome the need for ground-truth labels by introducing an unsupervised image-to-image translation deep learning model called thevessel segmentation generative adversarial network(VAN-GAN). VAN-GAN integrates synthetic blood vessel networks that closely resemble real-life anatomy into its training process and learns to replicate the underlying physics of the PAI system in order to learn how to segment vasculature from 3D biomedical images. With a variety ofin silico, in vitroandin vivodata, including patient-derived breast cancer xenograft models, we show that VAN-GAN facilitates accurate and unbiased segmentation of 3D vascular networks from PAI data volumes. By leveraging synthetic data to reduce the reliance on manual labelling, VAN-GAN lowers the barrier to entry for high-quality blood vessel segmentation to benefit users in the life sciences applying PAI to studies of vascular structure and function.
Cell-autonomous BMP signalling plays a key role in the maintenance of tumour cell EMT and migration programs in human ovarian carcinoma
Authors: Joun George , Zolghadr Fatemeh , Chakraborty Priyanka , Loan Le Thi Yen , Chong James J.H. ,   Australian Ovarian Cancer Study Group, Bowtell David D. L. , DeFazio Anna , Jolly Mohit Kumar , Seyedasli Naisana 
Published: April 2023

AbstractEpithelial-mesenchymal transition (EMT) plays a key role in tumour initiation, metastasis and resistance to therapy. Cells undergoing EMT, assume multiple semi-stable transitional states along the epithelial-mesenchymal axis that necessitates tight regulatory cascades. Although more is known about pathways involved in the initial induction of EMT, cascades that mediate/maintain the transitional states and/or the final mesenchymal phenotype are yet to be elucidated. In this study, we have assessed the role of bone morphogenic protein (BMP) signalling pathway in the regulation of cancer cell EMT and migration. Mining existing data from ovarian carcinomas, we defined the BMP pathway among the key pathways enriched in tumours with elevated EMT signatures, with a significant correlation in the expression of EMT markers with BMP ligands and downstream targets of the BMP pathway. Functional inhibition of the BMP pathway in ovarian cancer cells by a small molecule inhibitor, DMH1, resulted in impaired migration and depressed EMT signatures in bothin vitroandin vivomodels. Finally, ectopic induction of EMT in ovarian cancer cells through activation of an independent pathway, TNFα, resulted in the selective induction of Smad-mediated BMP pathway suggesting a role in maintenance of EMT, secondary to EMT induction.
Adaptive Bayesian Optimization for State-Dependent Brain Stimulation
Authors: Dabiri Sina , Cole Eric R. , Gross Robert E. 
Published: April 2023

AbstractBrain stimulation has become an important treatment option for a variety of neurological and psychiatric diseases. A key challenge in improving brain stimulation is selecting the optimal set of stimulation parameters for each patient, as parameter spaces are too large for brute-force search and their induced effects can exhibit complex subject-specific behavior. To achieve greatest effectiveness, stimulation parameters may additionally need to be adjusted based on an underlying neural state, which may be unknown, unmeasurable, or challenging to quantifya priori. In this study, we first develop a simulation of a state-dependent brain stimulation experiment using rodent optogenetic stimulation data. We then use this simulation to demonstrate and evaluate two implementations of an adaptive Bayesian optimization algorithm that can model a dynamically changing response to stimulation parameters without requiring knowledge of the underlying neural state. We show that, while standard Bayesian optimization converges and overfits to a single optimal set of stimulation parameters, adaptive Bayesian optimization can continue to update and explore as the neural state is changing and can provide more accurate optimal parameter estimation when the optimal stimulation parameters shift. These results suggest that learning algorithms such as adaptive Bayesian optimization can successfully find optimal state-dependent stimulation parameters, even when brain sensing and decoding technologies are insufficient to track the relevant neural state.
Operationalizing transparency in supply chains using a systematic literature review and graph theoretic approach
Authors: Faisal Mohd. Nishat , Sabir Lamay Bin , Sharif Khurram Jahangir 
Published: April 2023

PurposeThis study has two major objectives. First, comprehensively review the literature on transparency in supply chain management. Second, based on a critical analysis of literature, identify the attributes and sub-attributes of supply chain transparency and develop a numerical measure to quantify transparency in supply chains.Design/methodology/approachA systematic literature review (SLR) was conducted using the PRISMA approach. Utilizing SCOPUS database past eighteen-year papers search resulted in 249 papers to understand major developments in the domain of supply chain transparency. Subsequently, graph theoretic approach is applied to quantify transparency in supply chain and the proposed index is evaluated for case supply chains from pharma and dairy sectors.FindingsIt can be concluded from SLR that supply chain transparency research has evolved from merely tracking and tracing of the product towards sustainable development of the whole value chain. The research identifies four major attributes and their sub-attributes that influence transparency in supply chains, which are used to develop transparency index. The proposed index for two sectors helps to understand areas that need immediate attention to improve transparency in the case supply chains.Originality/valueThis paper attempts to understand the development of transparency research in supply chain using the PRISMA approach for SLR. In addition, development of mathematical model to quantify supply chain transparency is a novel attempt that would help benchmark best practices in the industry. Further, transparency index would help to understand specific areas that need attention to improve transparency in supply chains.
When and why workplace cyberbullying influences intention to stay: role of workplace social capital and affective commitment
Authors: Ciby Mariam Anil , Sahai Shikha 
Published: April 2023

PurposeCOVID-19 pandemic has accelerated the adoption of home-based teleworking globally. Coupled with this, there are rising concerns about workplace cyberbullying. However, less studies have explored workplace cyberbullying in non-western countries. The purpose of the current study is to examine whether workplace cyberbullying affects employees' intention to stay and to find out the mechanisms underlying the relationship.Design/methodology/approachData were collected among Indian home-based teleworkers. Data were analysed using SmartPLS and SPSS-PROCESS macro.FindingsResults show that workplace cyberbullying negatively impacts intention to stay and affective commitment acts as a mediator between this link. The results also reveal that workplace social capital moderates the negative effects of workplace cyberbullying on affective commitment. The results further confirm that workplace social capital moderated the indirect impact of workplace cyberbullying on intention to stay via affective commitment.Practical implicationsThis study highlights the potential of leveraging workplace social capital in order to reduce the negative effects of workplace cyberbullying.Originality/valueThese findings can complement the previous studies on the impact of negative work events on affective commitment and intention to stay as well as extend researchers' understanding of the underlying mechanism between workplace cyberbullying and intention to stay. Furthermore, this research explains how employees can utilise social resources from workplace social capital to mitigate the negative outcomes of workplace cyberbullying.
Wage premium and master's degrees: some empirical evidence from Spain
Authors: Caparrós Ruiz Antonio 
Published: April 2023

PurposeThe current expansion of the knowledge economy and its requirements of highly educated workers make interesting to analyse the effects on the labour market outcomes of completing a master's degree. This study examines the factors determining the probability of pursuing a postgraduate programme and observes whether workers reaching this educational attainment reap the benefits of their human capital investment through better paid jobs compared to college-only degree holders. On the other hand, it analyses whether individuals with a master's degree are more prone to upward wage mobility.Design/methodology/approachThe study relies on data obtained from the second survey on the Labour Insertion of University Graduates conducted by the National Statistics Institute (INE, 2019). This survey allows us to observe labour market transitions of the first group of Spanish university graduates under the European Higher Education Area (EHEA) and their earnings. The methodological procedure consists of the estimation of wage models controlling for the unobservable differences between workers who have or have not completed a master's degree.FindingsThe results indicate a significant positive impact of master's degree on salaries. Furthermore, individuals with postgraduate studies are more prone to upward wage mobility in comparison to college-only degree holders.Research limitations/implicationsData used does not allow us to identify which competences associated with the completion of a master's degree are more remunerated by employers.Practical implicationsThe econometric specification applied allows us to compute the direct effect of a master's degree on wages and predict the average probability that an individual is in a determined wage interval according to the knowledge area and controlling by the rest of characteristics.Social implicationsThe findings are helpful to diagnose and understand how the knowledge acquired through postgraduate studies are rewarded by the labour market, which is essential to evaluate the return on educational investments when making decisions about whether or not to continue postgraduate studies.Originality/valueThis research addresses novelty aspects on tertiary education in Spain and its effects on workers' careers.
Employee association in Japanese family and non-family SMEs
Authors: Matsuura Tsukasa , Noda Tomohiko 
Published: April 2023

PurposeThis study aims to investigate the nature of employee associations (EAs) and whether the EAs function as a collective voice similar to enterprise unions in Japanese small- and medium-sized enterprises by clarifying the differences in the determinants and effects between EAs and unions.Design/methodology/approachThe authors analyze 2,440 Japanese small- and medium-sized firms for determinants of unions and EAs. Using the bivariate probit model, the authors examine whether EAs complement (a way station to unionization) or substitute for (dampening the desire for unionization) traditional unionization. Furthermore, the effects of EAs and unions on voluntary employee turnover rates are compared.FindingsThe authors' findings regarding EAs are as follows: (1) although owner-managers are averse to both unions and EAs, owner-managers are not as averse to EAs as to unions; (2) EAs reduce the turnover rate to the same extent as unions do and (3) EAs are voice institutions that are less affected by the influence of unions.Research limitations/implicationsThe limitations of this study are as follows: (1) the dataset is slightly outdated; (2) due to the absence of panel data, the authors could not capture unobserved time-invariant factors that are the primary sources of endogeneity and (3) to overcome this vulnerability, the authors were able to control for the characteristics of management but not for the characteristics of employees because of a lack of information.Originality/valueThis study clarifies that non-union employee representation (NER) has the unique feature of being neither complementary nor substitutive to unions in Japan's industrial relations. EAs are organized not for union avoidance by employers, but voluntarily by employees without the aim of unionization. The associations have the same function as unions in reducing the turnover rate by resolving employees' grievances as entities independent from management.
The effects of knowledge sharing on innovative behaviours of academicians; mediating effect of innovative organization culture and quality of work life
Authors: Budur Taylan , Demirer Halil , Rashid Chnar Abdullah 
Published: April 2023

PurposeCurrent article aims to investigate the positive link between knowledge sharing (KS), innovative culture (IC), quality of work life (QWL) and innovative behaviours (IB) at higher education institutions in Iraq's Kurdistan Region.Design/methodology/approachThe study's data was gathered from academic staff at various universities in Iraq's Kurdistan Region. A total of 212 data were collected via survey questionnaire and analysed using structural equation modelling.FindingsIt was discovered that KS has direct and significant positive effects on IC, QWL and IB; IC had direct positive effects on IB; QWL had no considerable influence on IB and IC had a significant mediation and moderation roles between KS and IB. As a result, it is advised that universities in the region are strongly support IC to increase IB among academicians.Research limitations/implicationsFirstly, the data has been collected during the crises time that the lecturers were not receiving regular salary. This might change their quality work life perception. Secondly, data has been collected only from Sulaymaniyah city; other parts of the Iraq could have different perceptions. Lastly, sample size might be another limitation of the study.Practical implicationsIt is recommended that universities in the region should strongly support IC to increase IB among academicians, in terms of providing flexible working schedule and conditions, fair opportunities for promotion, and share decision making responsibilities.Social implicationsKS and IC has significant impacts on IB among the academicians. Accordingly, university administrative should improve policies increase KS behaviours and provide IC that academicians feel more comfortable culture to be innovative. Therefore, current paper recommends, tolerance to failure, openness to new ideas and participation to the decisions to improve IB among the academicians.Originality/valueThe paper is important that investigate KS and IC at the higher education institutions in Kurdistan region. Further, QWL perception has been investigated respectively. However, it has been observed that lecturers do not have quality of life perception at the investigated period of time.