bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-volume, label-free imaging for quantifying single-cell dynamics in induced pluripotent stem cell colonies
Authors: Asmar Anthony , Benson Zack , Peskin Adele P. , Chalfoun Joe , Simon Mylene , Halter Michael , Plant Anne 
Published: September 2023

AbstractTo facilitate the characterization of unlabeled induced pluripotent stem cells (iPSCs) during culture and expansion, we developed an AI pipeline for nuclear segmentation and mitosis detection from phase contrast images of individual cells within iPSC colonies. The analysis uses a 2D convolutional neural network (U-Net) plus a 3D U-Net applied on time lapse images to detect and segment nuclei, mitotic events, and daughter nuclei to enable tracking of large numbers of individual cells over long times in culture. The analysis uses fluorescence data to train models for segmenting nuclei in phase contrast images. The use of classical image processing routines to segment fluorescent nuclei precludes the need for manual annotation. We optimize and evaluate the accuracy of automated annotation to assure the reliability of the training. The model is generalizable in that it performs well on different datasets with an average F1 score of 0.94, on cells at different densities, and on cells from different pluripotent cell lines. The method allows us to assess, in a non-invasive manner, rates of mitosis and cell division which serve as indicators of cell state and cell health. We assess these parameters in up to hundreds of thousands of cells in culture for over 20 hours, at different locations in the colonies, and as a function of excitation light exposure.
Mitochondrial regulator PGC-1a in neuronal metabolism and brain aging
Authors: Souder Dylan C , McGregor Eric R , Rhoads Timothy W , Clark Josef P , Porter Tiaira J , Eliceiri Kevin , Moore Darcie L , Puglielli Luigi , Anderson Rozalyn M 
Published: September 2023

AbstractThe brain is a high energy tissue, and the cell types of which it is comprised are distinct in function and in metabolic requirements. The transcriptional co-activator PGC-1a is a master regulator of mitochondrial function and is highly expressed in the brain; however, its cell-type specific role in regulating metabolism has not been well established. Here, we show that PGC-1a is responsive to aging and that expression of the neuron specific PGC-1a isoform allows for specialization in metabolic adaptation. Transcriptional profiles of the cortex from male mice show an impact of age on immune, inflammatory, and neuronal functional pathways and a highly integrated metabolic response that is associated with decreased expression of PGC-1a. Proteomic analysis confirms age-related changes in metabolism and further shows changes in ribosomal and RNA splicing pathways. We show that neurons express a specialized PGC-1a isoform that becomes active during differentiation from stem cells and is further induced during the maturation of isolated neurons. Neuronal but not astrocyte PGC-1a responds robustly to inhibition of the growth sensitive kinase GSK3b, where the brain specific promoter driven dominant isoform is repressed. The GSK3b inhibitor lithium broadly reprograms metabolism and growth signaling, including significantly lower expression of mitochondrial and ribosomal pathway genes and suppression of growth signaling, which are linked to changes in mitochondrial function and neuronal outgrowth. In vivo, lithium treatment significantly changes the expression of genes involved in cortical growth, endocrine, and circadian pathways. These data place the GSK3b/PGC-1a axis centrally in a growth and metabolism network that is directly relevant to brain aging.
Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus
Authors: Curto Yasmina , Carceller Héctor , Klimczak Patrycja , Perez-Rando Marta , Wang Qing , Grewe Katharina , Kawaguchi Riki , Rizzoli Silvio , Geschwind Daniel , Nave Klaus-Armin , Teruel-Marti Vicent , Singh Manvendra , Ehrenreich Hannelore , Nácher Juan 
Published: September 2023

SummaryErythropoietin (EPO) aids in rectifying hippocampal transcriptional networks and synaptic structures of pyramidal lineages, thereby mitigating mood and cognition-associated disorders. An imminent conundrum is how EPO restores synapses by involving interneurons. By analyzing ∼ 12,000 single-nuclei transcriptomic data, we generated a comprehensive molecular atlas of hippocampal interneurons, resolved into 15 interneuron subtypes. Next, we studied molecular alterations upon recombinant human (rh)EPO and saw that gene expression changes relate to synaptic structure, trans-synaptic signaling and intracellular catabolic pathways. Putative ligand-receptor interactions between pyramidal and inhibitory neurons, regulating synaptogenesis, are altered upon rhEPO. An array ofin/ex vivoexperiments confirms that specific interneuronal populations exhibit reduced dendritic complexity, synaptic connectivity, and changes in plasticity-related molecules. Metabolism and inhibitory potential of interneuron subgroups are compromised, leading to greater excitability of pyramidal neurons. To conclude, improvement by rhEPO of neuropsychiatric phenotypes may partly owe to restrictive control over interneurons, facilitating re-connectivity and synapse development.
Decoding time-resolved neural representations of orientation ensemble perception
Authors: Yashiro Ryuto , Sawayama Masataka , Amano Kaoru 
Published: September 2023

ABSTRACTThe visual system is capable of computing summary statistics of multiple visual elements at a glance. While numerous studies have demonstrated ensemble perception across different visual features, the timing at which the visual system forms an ensemble representation remains unclear. This is mainly because most previous studies did not uncover time-resolved neural representations during ensemble perception. Here we used orientation ensemble discrimination tasks along with EEG recordings to decode orientation representations over time while human observers discriminated an average of multiple orientations. We observed alternation in orientation representations over time, with stronger neural representations of the individual elements in a set of orientations, but we did not observe significantly strong representations of the average orientation at any time points. We also found that a cumulative average of the orientation representations over approximately 500 ms converged toward the average orientation. More importantly, this cumulative orientation representation significantly correlated with the individual difference in the perceived average orientation. These findings suggest that the visual system gradually extracts an orientation ensemble, which may be represented as a cumulative average of transient orientation signals, through selective processing of a subset of multiple orientations that occurs over several hundred milliseconds.
Cellular complexity and crosstalk in murine TNF-dependent ileitis: Different fibroblast subsets propel spatially defined ileal inflammation through TNFR1 signalling
Authors: Iliopoulou Lida , Tzaferis Christos , Prados Alejandro , Roumelioti Fani , Koliaraki Vasiliki , Kollias George 
Published: September 2023

AbstractCrohn’s disease represents a persistent inflammatory disorder primarily affecting the terminal ileum. Through the application of single-cell RNA sequencing, we unveil the intricate cellular complexities within murine TNF-dependent ileitis, developing inTnfΔAREmice. Detailed immune cell analysis highlights B cell expansion, T cell effector reprogramming, and macrophage lineage shifts during inflammation. Focusing on stromal cells, we reveal a strong pro-inflammatory character, acquired by all fibroblast subsets, which exhibit complex communication patterns with the infiltrating immune and surrounding stromal cells. Interestingly, we identify thatTnfΔARE-induced ileitis is initiated in the lamina propria via TNFR1 pathway activation in villus-associated fibroblasts (Telocytes and Pdgfralowcells). Furthermore, we unveil separate spatial subsets of fibroblasts acting as exclusive responders to TNF, each orchestrating inflammation in different intestinal layers. Additionally, manipulating theTnfrsf1agene exclusively in fibroblast subsets suggests that inflammation is initiated by telocytes and Pdgfralowcells, while trophocytes drive its progression. This introduces novel evidence of spatial regulation of inflammation by fibroblast subsets, inciting and advancing disease in different layers of the gut. These findings underscore the pivotal role of fibroblasts in the inception and advancement of ileitis, proposing that targeting different fibroblast populations could impede the disease development and chronicity of inflammation.
Inhibition of the macrophage demethylase LSD1 reversesLeishmania amazonensis-induced transcriptomic changes and causes a decrease in parasite load
Authors: Gutiérrez-Sanchez Maria , Zhang Sheng , Gharsallah Charfeddine , Lamotte Suzanne , Varet Hugo , Rachel Legendre , Dingli Florent , Loew Damarys , Rotili Dante , Valente Sergio , Mai Antonello , Loiseau Philippe , Pomel Sébastien , Jung Manfred , Lecoeur Hervé , Prina Eric , Späth Gerald F. 
Published: September 2023

ABSTRACTIntracellular pathogens exploit host cell functions to favor their own survival. In recent years, the subversion of epigenetic regulation has emerged as a key microbial strategy to modify host cell gene expression and evade antimicrobial immune responses. Using the protozoan parasiteLeishmaniaas a model system, we have recently demonstrated that infection causes histone H3 hypomethylation, which is associated with the establishment of an anti-inflammatory phenotype, suggesting that host cell demethylases may play a role in the intracellular survival of these parasites. In this study, we employed a combination of pharmacological, RNA sequencing and interaction studies to investigate the role of the macrophage lysine demethylase LSD1 (KDM1a) inLeishmaniaintracellular infectionin vitro. Treatment of infected macrophages with two validated LSD1-specific inhibitors resulted in a significant reduction in parasite burden. We confirmed the impact of these inhibitors on LSD1 activity within macrophage nuclear extracts using anin vitrodemethylase assay and established their LSD1 target engagementin situby cellular thermal shift assay. RNA-seq analysis of infected and inhibitor-treated macrophages linked parasite killing to a partial reversion of infection-dependent expression changes, restoring the macrophage anti-microbial response and limiting cholesterol biosynthesis. While we ruled out any impact ofLeishmaniaon LSD1 expression or localization, we uncovered significant alterations in LSD1 complex formation within infected macrophages, involving unique interactions with host proteins as well as interactions withLeishmaniaproteins that appear to be secreted into the macrophage nucleus. Our study sheds important new light on the epigenetic mechanisms of macrophage immuno-metabolic subversion by intracellularLeishmaniaand identifies LSD1 as a potential candidate for host-directed, anti-leishmanial therapy.
Degraded tactile coding in the Cntnap2 mouse model of autism
Authors: Wang Han Chin , Feldman Daniel E. 
Published: September 2023

AbstractAtypical sensory processing in autism involves altered neural circuit function and neural coding in sensory cortex, but the nature of coding disruption is poorly understood. We characterized neural coding in L2/3 of whisker somatosensory cortex (S1) ofCntnap2-/-mice, an autism model with pronounced hypofunction of parvalbumin (PV) inhibitory circuits. We tested for both excess spiking, which is often hypothesized in autism models with reduced inhibition, and alterations in somatotopic coding, using c-fos immunostaining and 2-photon calcium imaging in awake mice. InCntnap2-/-mice, c- fos-(+) neuron density was elevated in L2/3 of S1 under spontaneous activity conditions, but comparable to control mice after whisker stimulation, suggesting that sensory-evoked spiking was relatively normal. 2-photon GCaMP8m imaging in L2/3 pyramidal cells revealed no increase in whisker-evoked response magnitude, but instead showed multiple signs of degraded somatotopic coding. These included broadening of whisker tuning curves, blurring of the whisker map, and blunting of the point representation of each whisker. These altered properties were more pronounced in noisy than sparse sensory conditions. Tuning instability, assessed over 2-3 weeks of longitudinal imaging, was also significantly increased inCntnap2-/-mice. Thus,Cntnap2-/-mice show no excess spiking, but a degraded and unstable tactile code in S1.
We set them up for failure: performativity, corporate reporting and decolonisation
Authors: Norris Ellie , Kutubi Shawgat , Greenland Steven , Wallace Ruth 
Published: September 2023

PurposeThis research aims to examine the performativity of corporate reports as an example of an accounting inscription that can frame the relationship between Aboriginal and Torres Strait Islander entities and their stakeholders. The framing and overflow effects of these reports have been explored to consider whether they strengthen or undermine the reputation and capability of these community-controlled entities.Design/methodology/approachAligned with actor–network theory and a decolonising research protocol, qualitative interviews were conducted with senior managers and directors of Aboriginal and Torres Strait Islander entities and their key stakeholders to explore their experiences of corporate reporting. Additional analysis of these organisations' annual reports was conducted to corroborate key reporting themes.FindingsThis research has identified a dual role for corporate reporting, simultaneously framing performance against an expectation of failure, but with the potential for accounting inscriptions to highlight positive contributions to cultural and community priorities. It also indicates the need for sector specifics within the reporting frameworks and adequate resourcing for Aboriginal and Torres Strait Islander entities to meet reporting obligations.Practical implicationsThis research makes policy-based recommendations in terms of user-driven and culturally informed performance measures. It also highlights the importance of adequate funding for Aboriginal and Torres Strait Islander entities to carry out meaningful performance evaluations beyond the preparation of financial statements.Originality/valueOne of the few empirical studies to capture the performativity of accounting inscriptions from the perspective of Aboriginal and Torres Strait Islander entities. This sector has received minimal attention within the accounting discipline, despite significantly contributing to community well-being and cultural protection. There is emancipatory potential via policy frameworks that resonate with Aboriginal and Torres Strait Islander cultural beliefs and practices.
CEO successions in times of decline and prosperity: restoring aspiration and performance implications in family firms
Authors: Calabrò Andrea , Torchia Mariateresa , Yezza Hedi , Quarato Fabio 
Published: September 2023

PurposeThe aim of this paper is to develop and test a behavioral theory of chief executive officer (CEO) succession and its performance consequences in family firms. Building upon performance feedback and slack research, the study hypothesizes that the effect of selecting a non-family outsider CEO on post-succession firm performance is contingent upon pre-succession firm performance aspirations level and the available slack resources.Design/methodology/approachThe hypotheses are tested using a panel of 430 CEO successions in Italian family firms.FindingsThe findings show that a non-family outsider CEO is particularly valuable when performance resides far below aspiration levels, and there is a high availability of slack resources.Originality/valueThe study provides novel insights of the benefits and drawbacks of selecting non-family outsider CEOs offering behavioral-based theoretical explanations of performance consequences of CEO successions.
The role of ethical leadership and psychological capital in influencing employee attitudes: a moderated-mediation model
Authors: Loghman Saeed , Quinn Michael , Dawkins Sarah , Scott Jenn 
Published: September 2023

PurposeResearch has consistently demonstrated that psychological capital (PsyCap) is an important predictor of various employee outcomes. Despite this, there is a paucity of knowledge regarding antecedents of PsyCap and the boundary conditions that influence PsyCap relationships. This study aimed to address these gaps by investigating how ethical leadership (EL) influences employee PsyCap, and in turn, predicts a range of desirable and undesirable employee attitudes. Furthermore, the study examined the moderating role of length of the leader-follower relationship (LLR) and organisational identification in these relationships in a novel moderated-mediation model.Design/methodology/approachData were collected from 269 full-time employees in Australia via an online survey across two time-points.FindingsThe results show that PsyCap mediates the relationship between EL and employee attitudes. The results also indicate that LLR moderates these relationships, whereby these relationships are strengthened as LLR increases.Originality/valueThis study responds to calls for further investigation of antecedent and outcome variables related to PsyCap, as well as moderators of the relationships between PsyCap and antecedent and outcome variables. The findings also extend the application of social exchange theory to the context of EL and PsyCap.
Do all CEO pay regulations hurt firm performance? Evidence from China
Authors: Tong Xiaochuan , Wang Weijie , Liu Yaowu 
Published: September 2023

PurposeThe authors study and compare the effects of three CEO compensation restricting policies issued by the Chinese government in 2009, 2012 and 2015. This paper aims to shed light on the conditions under which CEO compenstation can be effectively regulated without negatively affecting firm performance. Design/methodology/approachThese policies targeted state-owned enterprises (SOEs), especially central state-owned enterprises (CSOEs). Using these policies as natural experiments, the authors investigate how their effects differ on CEO compensation, firm performance and two known performance-decreasing mechanisms: perk consumption and tunneling activities.FindingsThe authors show that restricting CEO pay does not necessarily backfire in terms of deteriorating firm performance. This non-decreasing firm performance can be achieved by restricting perk consumption and tunneling activities while introducing CEO pay regulations.Originality/valueThe authors exploit a powerful experimental setting in the context of China. The evidence contributes to the literature on CEO pay regulations and is relevant to the managerial decisions of policy makers and boards of directors.
Strategies for the ISO 9001 certification life cycle (StrategISO)
Authors: Cândido Carlos J.F. 
Published: September 2023

PurposeCertified and non-certified organisations must make strategic decisions regarding ISO 9001 adoption, maintenance, renewal and abandonment. However, the ISO 9001 literature lacks a typology of the strategic options available to these organisations. The purpose of this conceptual study is to develop a framework of the alternative strategies for the stages of the ISO 9001 life cycle (implementation/certification, certification maintenance and recertification/decertification stages).Design/methodology/approachThe research method is based on literature review, selection of relevant variables and synthesis of coherent alternative strategies.FindingsResults include the main variables of relevance for the definition of the ISO 9001 strategies (e.g. life cycle stage, organisational motivations, barriers, benefits, internalisation degree and quality of the certification body), the main situations in which organisations can find themselves (in terms of ISO 9001 certification, maintenance and decertification), the strategic options for each situation (e.g.: certify, maintain certification, try harder, change certification body, intensify learning and experimentation with ISO 9001) and the implications and consequences of such options. Research results are integrated into a strategy framework, composed of three strategy matrices, one for each stage of the life cycle. The matrices present the strategic situations, available strategic alternatives and benefits of the strategies.Originality/valueThis study combines the results of previous research to develop an original strategy framework, which constitutes the main research contribution. As far as the author is aware, there is no such strategy framework in the literature. The framework has relevant implications for theory and practice and helps to identify future research directions.
We're all in this together: addressing post-pandemic challenges of Indian rural society
Authors: Gupta Aanchal , Singh Samar 
Published: September 2023

PurposeThis qualitative study explores how technologically challenged Indian rural communities adjusted to the tech-driven work system successfully in the post-pandemic era.Design/methodology/approachQualitative semi-structured interviews with multiple Indian rural households conducted in the years 2021 and 2022 were employed.FindingsThe findings highlight the critical role played by the social capital in addressing the issues that Indian rural communities were facing in their work setting as a direct result of the COVID-19 outbreak. The embedded social network and social values in rural society came to the rescue when other tangible resources were not available for everyone.Research limitations/implicationsThis study contributes to Bourdieu's theory of Social Capital by discovering that social capital can be utilized to gain existential advantages in extraordinary circumstances of (work) life.Practical implicationsPolicymakers should acknowledge the presence of social capital in societies, especially rural ones. Social capital plays a significant role in the execution of relevant society-level tasks and can further help in dealing with certain materialistic impediments.Social implicationsInvestments in community infrastructure, education and communication strategies can enhance social capital's role in crisis response.Originality/valueThis study is original as it is the first one that studies the significance of social capital in a post-pandemic environment, especially when the availability of required technological resources is rare.