bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular and functional characterization of different BrainSphere models for use in neurotoxicity testing on microelectrode arrays
Authors: Hartmann Julia , Henschel Noah , Bartmann Kristina , Dönmez Arif , Brockerhoff Gabriele , Koch Katharina , Fritsche Ellen 
Published: March 2023

AbstractThe currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low testing throughput hinder their application for large numbers of chemicals. To overcome these limitations,in vitromethods are currently developed which are based on human induced pluripotent stem cells (hiPSC) that allow higher testing throughput at lower costs. We applied six different protocols to generate 3D BrainSphere models for acute NT evaluation. These include three different media for 2D neural induction and two media for subsequent 3D differentiation resulting in self-organized, organotypic neuron/astrocyte microtissues. All induction protocols yielded nearly 100 % nestin-positive hiPSC-derived neural progenitor cells (hiNPCs) yet with different gene expression profiles concerning regional patterning. Moreover, gene expression and immunocytochemistry analyses revealed that the choice of media determines neural differentiation patterns. On the functional level, BrainSpheres exhibited different levels of electrical activity on microelectrode arrays (MEA). Spike sorting allowed BrainSphere functional characterization with the mixed cultures consisting of GABAergic, glutamatergic, dopaminergic, serotonergic, and cholinergic neurons. A test method for acute NT testing, the human multi-neurotransmitter receptor (hMNR) assay, was proposed applying such MEA-based spike sorting. These models are not only promising tools in toxicology but also for drug development and disease modeling.
Evolutionary rescue under demographic and environmental stochasticity
Authors: Xu Kuangyi , Vision Todd J. , Servedio Maria R. 
Published: March 2023

AbstractWild populations suffer two types of stochasticity: demographic stochasticity, from sampling error in offspring number, and environmental stochasticity, from temporal variation of the growth rate. By modeling evolution through phenotypic selection following an abrupt environmental change, we investigate how genetic and demographic dynamics, as well as effects of selection intensity after the environmental change and genetic variance on population survival, differ under demographic and environmental stochasticity. We find that the survival probability declines sharply with stronger selection under demographic stochasticity, but declines more continuously under environmental stochasticity. However, the genetic variance that confers the highest survival probability differs little under demographic and environmental stochasticity. Since the influence of demographic stochasticity is stronger when population size is smaller, a slow initial decline of genetic variance which allows quicker evolution and increase of fitness, is important for persistence. In contrast, the influence of environmental stochasticity is density-independent, so higher initial fitness becomes important for survival under strong environmental stochasticity. Combining both types of stochasticity shows that adding even weak environmental stochasticity can exaggerate the effects of different levels of demographic stochasticity on survival probabilities. Our work suggests the importance of explicitly distinguishing and measuring the forms of stochasticity for evolutionary rescue studies.
Auditory dyadic interactions through the ‘eye’ of the social brain: How visual is the posterior STS interaction region?
Authors: Landsiedel Julia , Koldewyn Kami 
Published: March 2023

AbstractHuman interactions contain potent social cues that not only meet the eye but also the ear. Although research has identified a region in the posterior superior temporal sulcus as being particularly sensitive to visually presented social interactions (SI-pSTS), its response to auditory interactions has not been tested. Here, we used fMRI to explore brain response to auditory interactions, with a focus on temporal regions known to be important in auditory processing and social interaction perception. In Experiment 1, monolingual participants listened to two-speaker conversations (intact or sentence-scrambled) and one-speaker narrations in both a known and unknown language. Speaker number and conversational coherence were explored in separately localised regions-of-interest (ROI). In Experiment 2, bilingual participants were scanned to explore the role of language comprehension. Combining univariate and multivariate analyses, we found initial evidence for a heteromodal response to social interactions in SI-pSTS. Specifically, right SI-pSTS preferred auditory interactions over control stimuli and represented information about both speaker number and interactive coherence. Bilateral temporal voice areas (TVA) showed a similar, but less specific, profile. Exploratory analyses identified another auditory-interaction sensitive area in anterior STS. Indeed, direct comparison suggests modality specific tuning, with SI-pSTS preferring visual information while aSTS prefers auditory information. Altogether, these results suggest that right SI-pSTS is a heteromodal region that represents information about social interactions in both visual and auditory domains. Future work is needed to clarify the roles of TVA and aSTS in auditory interaction perception and further probe right SI-pSTS interaction-selectivity using non-semantic prosodic cues.Highlights-Novel work investigating social interaction perception in the auditory domain.-Visually defined SI-pSTS shows a heteromodal response profile to interactions.-Yet, it prefers visual to auditory stimuli. The reverse was found for anterior STS.-Temporal voice areas show qualitatively different response compared to SI-pSTS.-Future studies are needed to corroborate the unique role of right SI-pSTS.
GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage
Authors: Vcelkova Terezia , Reiter Wolfgang , Zylka Martha , Hollenstein David M. , Schuckert Stefan , Hartl Markus , Seiser Christian 
Published: March 2023

AbstractPost-translational modifications of histones are important regulators of the DNA damage response (DDR). By using affinity purification mass spectrometry (AP-MS) we discovered that genetic suppressor element 1 (GSE1) forms a complex with the HDAC1/CoREST deacetylase/demethylase co-repressor complex. In-depth phosphorylome analysis revealed that loss of GSE1 results in impaired DDR, ATR signalling and γH2AX formation upon DNA damage induction. Altered profiles of ATR target serine-glutamine motifs (SQ) on DDR-related hallmark proteins point to a defect in DNA damage sensing. In addition, GSE1 knock-out cells showed hampered DNA damage-induced phosphorylation on SQ motifs of regulators of histone post-translational modifications, suggesting altered histone modification. While loss of GSE1 does not affect the histone deacetylation activity of CoREST, GSE1 appears to be essential for binding of the deubiquitinase USP22 to CoREST and for the deubiquitination of H2B K120 in response to DNA damage. The combination of deacetylase, demethylase, and deubiquitinase activity makes the USP22-GSE1-CoREST subcomplex a multi enzymatic eraser that seems to play an important role during DDR. Since GSE1 has been previously associated with cancer progression and survival our findings are potentially of high medical relevance.
An oral cholera vaccine in the prevention and/or treatment of inflammatory bowel disease
Authors: Meunier Marine , Spillmann Adrian , Rousseaux Christel , Schwamborn Klaus , Hanson Melissa 
Published: March 2023

AbstractThe oral cholera vaccine WC-rBS consists of 4 different inactivated strains ofVibrio cholerae(LPS source) admixed with recombinant cholera toxin B subunit. Because of its unique composition and anti-inflammatory properties reported for both CTB and low doses of LPS from other Gram-negative bacteria, we speculated that WC-rBS might have anti-inflammatory potential in a chronic autoimmune disease such as inflammatory bowel diseases. Firstin vitroendotoxin tolerance experiments showed the surprising WC-rBS potential in the modulation of inflammatory responses on both PBMCs and THP1 cells. WC-rBS was further evaluated in the Dextran Sodium Sulfate colitis mouse model. Administrated orally at different dosages, WC-rBS vaccine was safe and showed immunomodulatory properties when administered in a preventive mode (before and during the induction of DSS colitis) as well as in a curative mode (after colitis induction); with improvement of disease activity index (from 27 to 73%) and histological score (from 65 to 88%). Interestingly, the highest therapeutic effect of WC-rBS vaccine was observed with the lowest dosage, showing even better anti-inflammatory properties than mesalamine; an approved 5-aminosalicylic acid drug for treating IBD patients. In summary, this is the first time that a prophylactic medicine, safe and approved for prevention of an infectious disease, showed a benefit in an inflammatory bowel disease model, potentially offering a novel therapeutic modality for IBD patients.
The fission yeast cytokinetic ring component Fic1 promotes septum formation
Authors: Rossi Anthony M. , Bohnert K. Adam , Gould Kathleen L. 
Published: March 2023

AbstractInSchizosaccharomyces pombeseptum formation is coordinated with cytokinetic ring constriction but the mechanisms linking these events are unclear. In this study, we explored the role of the cytokinetic ring component Fic1, first identified by its interaction with the F-BAR protein Cdc15, in septum formation. We found that thefic1phospho-ablating mutant,fic1-2A, is a gain-of-function allele that suppressesmyo2-E1, the temperature-sensitive allele of the essential type-II myosin,myo2. This suppression is achieved by the promotion of septum formation and required Fic1’s interaction with the F-BAR proteins Cdc15 and Imp2. Additionally, we found that Fic1 interacts with Cyk3 and that this interaction was likewise required for Fic1’s role in septum formation. Fic1, Cdc15, Imp2, and Cyk3 are the orthologs of theSaccharomyces cerevisiaeingression progression complex, which stimulates the chitin synthase Chs2 to promote primary septum formation. However, our findings indicate that Fic1 promotes septum formation and cell abscission independently of theS. pombeChs2 ortholog. Thus, while similar complexes exist in the two yeasts that each promote septation, they appear to have different downstream effectors.Summary StatementTheS. pombecytokinetic ring protein Fic1 promotes septum formation in a manner dependent on interactions with the cytokinetic ring components Cdc15, Imp2, and Cyk3.
Overexpression of IκBα modulates NF-κB activation of inflammatory target gene expression
Authors: Downton Polly , Bagnall James S , England Hazel , Spiller David G , Humphreys Neil , Jackson Dean A , Paszek Pawel , White Michael R H , Adamson Antony D 
Published: March 2023

AbstractCells respond to inflammatory stimuli such as cytokines by activation of the nuclear factor-κB (NF-κB) signalling pathway, resulting in oscillatory translocation of the transcription factor p65 between nucleus and cytoplasm to mediate immune response. We investigate the relationship between p65 and inhibitor-κBα (IκBα) protein levels and dynamic properties of the system, and how this interaction impacts on the expression of key inflammatory genes. Using bacterial artificial chromosomes, we developed new cell models of IκBα-eGFP protein overexpression in a native genomic context. We find that cells with high levels of the negative regulator IκBα remain responsive to inflammatory stimuli and maintain dynamics for both p65 and IκBα. In contrast, canonical target gene expression is dramatically reduced by overexpression of IκBα, but can be partially rescued by overexpression of p65. Treatment with leptomycin B to promote nuclear accumulation of IκBα also suppresses canonical target gene expression, suggesting a mechanism in which nuclear IκBα accumulation prevents productive p65 interaction with promoter binding sites. This causes reduced target promoter binding and gene transcription, which we validate by chromatin immune precipitation and in primary cells. Overall, we show how inflammatory gene transcription is modulated by the expression levels of both IκBα and p65, and that transcription can be partially decoupled from p65 protein dynamics. This results in an anti-inflammatory effect on transcription, demonstrating a broad mechanism to modulate the strength of inflammatory response.
HEATR5B associates with dynein-dynactin and selectively promotes motility of AP1-bound endosomal membranes
Authors: Madan Vanesa , Albacete Lucas Albacete , Jin Li , Scaturro Pietro , Watson Joseph L. , Muschalik Nadine , Begum Farida , Boulanger Jérôme , Bauer Karl , Kiebler Michael A. , Derivery Emmanuel , Bullock Simon L. 
Published: March 2023

ABSTRACTThe dynein motor complex mediates polarised trafficking of a wide variety of organelles, intracellular vesicles and macromolecules. These functions are dependent on the dynactin complex, which helps recruit cargoes to dynein’s tail region and activates motor movement. How dynein and dynactin orchestrate trafficking of diverse cargoes is unclear. Here, we identify HEATR5B, an interactor of the AP1 clathrin adaptor complex, as a novel player in dynein-dynactin function. HEATR5B is one of several proteins recovered in a biochemical screen for proteins whose association with the human dynein tail complex is augmented by dynactin. We show that HEATR5B binds directly to the dynein tail and dynactin and stimulates motility of AP1-associated endosomal membranes in human cells. We also demonstrate that the HEATR5B homologue inDrosophilais an essential gene that promotes dynein-based transport of AP1-bound membranes to the Golgi apparatus. As HEATR5B lacks the coiled-coil architecture typical of dynein adaptors, our data point to a non-canonical process orchestrating motor function on a specific cargo. We additionally show that HEATR5B promotes association of AP1 with endosomal membranes in a dynein-independent manner. Thus, HEATR5B co-ordinates multiple events in AP1-based trafficking.
Investigating sustainable consumption behaviors: a bibliometric analysis
Authors: Vergura Donata Tania , Zerbini Cristina , Luceri Beatrice , Palladino Rosa 
Published: March 2023

PurposeThe research carried out a bibliometric analysis of the literature on environmental sustainability from a demand perspective by analyzing the scientific contributions published in the last twenty years.Design/methodology/approachA bibliometric analysis was carried out to outline the scientific studies development, identifying the most discussed topics and those that would require future research. In total, 274 articles published between 1999 and 2021 were collected through the Web of Science database and analyzed with the SciMAT software.FindingsBy systematizing the literature results, the study revealed a steady growth in the number of publications and in the research areas, highlighting a substantial evolution of the research topic.Research limitations/implicationsThe study contribute for conceptual, methodological and thematic development of the topic, systematizing the results of existing studies and providing useful indications for the promotion of sustainable consumer habits.Originality/valueThe study attempts to bridge the gap in current literature by offering a holistic view on the role of consumer behavior in pursuing sustainability goals, identifying both the most treated areas and the emerging ones that can represent opportunities for future research.
Post-disaster research: challenges and opportunities conversation on disasters: deconstructed on 11th of June 2021
Authors: Beaven Sarah , Benouar Djillali , Bhatt Mihir , Gibson Terry , Peek Lori 
Published: March 2023

PurposeThis conversation presents the reflections from five prominent disaster scholars and practitioners on the opportunities and challenges associated with research following disasters and explores the importance of ethics in disaster research.Design/methodology/approachThis paper is based on the conversations that took place on Disasters: Deconstructed Podcast livestream on the 11th of June 2021.FindingsThe prominent themes in this conversation include ethical approaches to research, how we–as disaster researchers and practitioners–collaborate, engage, and cooperate, and whose voices are centred in a post-disaster research context.Originality/valueThe conversation contributes to ongoing discussions around the conduct and practice of disaster research.
Embedding the marketing angle into the pursuit of entrepreneurial propensity: roles of perceived feasibility and desirability and stakeholders' support
Authors: Kariv Dafna , Krueger Norris , Cisneros Luis , Kashy-Rosenbaum Gavriella 
Published: March 2023

PurposeThis study endeavors to decode the propensity for entrepreneurial action by addressing the perceptions of feasibility and desirability stemming from entrepreneurs' and non-entrepreneurs’ appraisal of holding marketing capabilities; complemented by the direct and indirect effects of market stakeholders' support, assessed as bridging or buffering the entrepreneurial action.Design/methodology/approachThree groups were formed from a random sample of 1,957 Canadian (from Quebec) respondents to an online questionnaire: non-entrepreneurs with low entrepreneurial intentions, non-entrepreneurs with high entrepreneurial intentions and entrepreneurs with high entrepreneurial intentions.FindingsThe analyses revealed salient effects of perceptions of feasibility and desirability, coupled with appraisals of possessing marketing capabilities, on entrepreneurial propensity; and their strengthened relations when obtaining stakeholders' support. Overall, the results suggest that perceived market feasibility and market desirability are prominent factors in differentiating between entrepreneurial and non-entrepreneurial action, and the type and function of stakeholders' support are prominent in differentiating between intentions.Practical implicationsPractical implications include facilitating the transmission of marketing knowledge to novice entrepreneurs through higher education and the ecosystem.Originality/valueThe authors show that perceptions of feasibility and desirability are particularly dependent on the entrepreneur's perceived marketing capabilities and perceptions of entrepreneurial ecosystem supportiveness. This study thus captures a fuller range of the intentions–action relationship by gauging the unidimensional approach to entrepreneurial action through intertwining attributes at the individual and market levels. It takes a new look at feasibility and desirability through marketing capabilities; and offers a more robust classification of stakeholders' support—institution/people, bridging/buffering. Practical implications include facilitating the transmission of marketing knowledge to novice entrepreneurs through higher education and the ecosystem.
Managers’ development environments: an integrative literature review
Authors: Reineholm Cathrine , Lundqvist Daniel , Wallo Andreas 
Published: March 2023

Purpose
The purpose of this paper is to assess previous research on conditions for managers’ learning and development in daily work practices and how such conditions may influence their sustainability and also to propose a concept and a heuristic model that reconceptualizes and expands on the theoretical foundations generated in previous studies of managers’ learning and development at work.

Design/methodology/approach
This paper is based on an integrative literature review. The literature search identified 1,403 unique studies. Nine qualitative and seven quantitative studies met the relevance and quality criteria and were included in the review.

Findings
The results of the review found associations between managers’ learning conditions, career opportunities, individual engagement and sustainability. However, the small amount of empirical data used in the reviewed studies and the cross-sectional design of the studies make it difficult to establish the nature of the relationship between different variables.

Practical implications
The results of this paper show that managers need to care for and take advantage of opportunities for their own development and not only function as creators of their employees’ development. Employers should keep in mind that the development environment includes managers and employees.

Originality/value
This paper contributes with an original concept of managers’ development environments and a conceptual model that integrates theory with results from the included studies. Based on the model, propositions that may serve as an agenda for future research are formulated.
Exploring the use of dual-processing in commercial property development decision-making under conditions of risk and uncertainty
Authors: Robson Simon , Greenhalgh Paul 
Published: March 2023

PurposeCommercial property development builds floor space in anticipation of potential, but unknown, future demand, making it particularly prone to risk and uncertainty. The research explores the degree to which property developer decision-making is objective and rational and the degree to which it relies on behavioural instincts and intuition. Decision-making theory, including heuristics, is considered and its prevalence in the field of commercial property development is examined.Design/methodology/approachA “dual-processing” decision-making model, comprising intuitive System 1 and objective System 2 processing, is proposed and tested. Inductive research using template analysis of interviews, with “high status” commercial property developers, explored whether the model offers an accurate representation of developers' behaviour and effective lens through which to examine decisions made under conditions of risk and uncertainty.FindingsParticipants believed they adopted objective and rational approaches to complex commercial property development decisions. Analysis of interviews reveals that System 1 heuristics and intuition play significant roles in decision-making behaviour, leading to potential bias and systematic error. The research concludes that the dual-processing model provides a useful lens through which to better understand the decision-making approach adopted by commercial property developers.Originality/valueThe research represents the rare application of behavioural theory to the realm of commercial property development and provides new and original insight as to how important investment decisions are made under conditions of risk and uncertainty, with implications for professional practice.