bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a terpene synthase arsenal using long-read sequencing and genome assembly ofAspergillus wentii
Authors: Olumakaiye Richard , Corre Christophe , Alberti Fabrizio 
Published: September 2024

ABSTRACTFungi are talented producers of secondary metabolites with applications in the pharmaceutical and agrochemical sectors.Aspergillus wentiiCBS 141173 has gathered research interest due to its ability to produce high-value norditerpenoid compounds, including anticancer molecules. In this study, we aimed to expand the genomic information available forA. wentiito facilitate the identification of terpenoid biosynthetic genes that may be involved in the production of bioactive molecules. Long-read genome sequencing ofAspergillus wentiiCBS 141173 was conducted using Oxford Nanopore Technologies (ONT) MinION MK1C. In addition, paired-end stranded RNA-seq data from two time points, 7 days and 30 days, was used for functional annotation of the assembled genome. Overall, we assembled a genome of approximately 31.2 Mb and identified 66 biosynthetic gene clusters from the annotated genome. Metabolic extracts ofA. wentiiwere analysed and the production of the bioactive terpenoid asperolide A was confirmed. We further mined the assembled and annotated genome for BGCs involved in terpenoid pathways using a combination of antiSMASH and local BlastP and identified 16 terpene synthases. Phylogenetic analysis was conducted and allowed us to establish relationships with other characterised terpene synthases. We identified two terpene clusters potentially involved in pimarane-like diterpenoid biosynthesis. Finally, the analysis of the 16 terpene synthases in our 7-day and 30-day transcriptomic data suggested that only four of them were constitutively expressed under laboratory conditions. These results provide a scaffold for the future exploration of terpenoid biosynthetic pathways for bioactive molecules inA. wentii. The terpenoid clusters identified in this study are candidates for heterologous gene expression and/or gene disruption experiments. The description and availability of the long-read genome assembly ofA. wentiiCBS 141173 further provides the basis for downstream genome analysis and biotechnological exploitation of this species.
Identification of neurodevelopmental organization of the cell populations of juvenile Huntington’s disease using dorso-ventral HD organoids and HD mouse embryos
Authors: Świtońska-Kurkowska Karolina , Kubiś Jakub , Delimata-Raczek Joanna , Krist Bart , Surdyka Magda , Kalinowska-Pośka Żaneta , Piasecki Piotr , Handschuh Luiza , Podkowiński Jan , Rakoczy Magdalena , Samelak-Czajka Anna , Hayden Michael , Caron Nicholas S , Figiel Maciej 
Published: September 2024

ABSTRACTHuntington’s disease (HD) is a polyglutamine neurodegenerative disease involving pathogenesis within the striatum and cerebral cortex and a neurodevelopmental component, particularly in juvenile HD form (JOHD). We established a fused HD dorsal-ventral system, imitating the cortex and striatum interaction in a single organoid to discover neurodevelopmental impairments at the level of cell populations. We found a range of early pathogenic phenotypes indicating that brain development in HD is affected by impaired neurogenesis. The phenotypes occurred already in early-stage 60-day organoids and the brain of humanized mouse embryos, at time of the beginning of the neurogenesis and choroid plexus development. We demonstrated that HD organoids and HD mouse embryonic brains had gene expression profiles of impaired maturation of neurons and increased expression of genes responsible for proliferation compared to genes responsible for differentiation in control organoids. By using scRNA-seq, the choroid plexus population was highly abundant in HD organoids and embryonic brains. Cortical and choroid plexus cell populations in HD organoids and brains co-expressed genes responsible forHTTfunction (mitotic spindle and cilia). The impaired maturation and the increased occurrence of the choroid plexus populations were mitigated in our compensatory model, mosaic dorsal/ventral (D/V) or V/D HD/control organoids. Finally, we found that TTR protein, a choroid plexus marker, is elevated in the adult HD mouse serum, indicating that TTR may be a promising marker for detecting HD. In summary, the fused dorso-ventral HD organoids identify a spectrum of neurodevelopmental features, including increased proliferation and delayed cell maturation. We demonstrate that the choroid plexus population is characteristic of aberrant HD neurodevelopment, and contains TTR marker, which can be translated as a blood marker in HD.
Adrenergic signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity
Authors: Guttenplan Kevin A. , Maxwell Isa , Santos Erin , Borchardt Luke A. , Manzo Ernesto , Abalde-Atristain Leire , Kim Rachel D , Freeman Marc R. 
Published: September 2024

AbstractHow astrocytes regulate neuronal circuits is a fundamental, unsolved question in neurobiology. Nevertheless, few studies have explored the rules that govern when astrocytes respond to different neurotransmittersin vivoand how they affect downstream circuit modulation. Here, we report an unexpected mechanism inDrosophilaby which G-protein coupled adrenergic signaling in astrocytes can control, or “gate,” their ability to respond to other neurotransmitters. Further, we show that manipulating this pathway potently regulates neuronal circuit activity and animal behavior. Finally, we demonstrate that this gating mechanism is conserved in mammalian astrocytes, arguing it is an ancient feature of astrocyte circuit function. Our work establishes a new mechanism by which astrocytes dynamically respond to and modulate neuronal activity in different brain regions and in different behavioral states.
Localized translation oferm-1contributes to ERM-1 function in theC. elegansembryo
Authors: van der Salm Elise , Koelewijn Esther , van der Maas Erica , Eeken Max , Ruijtenberg Suzan 
Published: September 2024

SummaryTranslation of mRNAs into proteins is a key step in decoding the information stored in the genome. Localized translation ensures that proteins are expressed where needed, which is important for cell-specific protein expression, the establishment of cellular protein gradients, and the creation of protein hotspots within different cellular compartments. Although localized translation is believed to be important for cell fate determination and organismal development, our understanding of localized translation in the context of living animals is limited, as few methods that allow direct visualization and measurement of translation exist. We adapted the SunTag-based single-molecule translation imaging system for use in Caenorhabditis elegans and showed the dynamics and importance of localizederm-1translation during development. We founderm-1translation to be enriched at the plasma membrane, overlapping with the localization and function of the encoded membrane-cytoskeleton linker ERM-1. Re-localizingerm-1translation to nuclear pores disrupts the function of ERM-1 protein, particularly its role in linking the actin cytoskeleton to the membrane. Our work demonstrates the power of translation imaging and highlights the importance of localized translation inC. elegansdevelopment.
Discovery of dehydroamino acids and their crosslinks in Tau and other aggregating proteins of Alzheimer’s disease
Authors: Markovich Samuel W. , Frey Brian L. , Scalf Mark , Shortreed Michael R. , Smith Lloyd M. 
Published: September 2024

AbstractBackgroundAlzheimer’s disease (AD) is characterized by accumulation of two types of protein aggregates, senile plaques and neurofibrillary tangles, which strongly contribute to the pathogenesis of the disease. Senile plaques consist primarily of aggregated amyloid-ß, while neurofibrillary tangles form via aggregation of the protein Tau, as well as other microtubule-associated proteins such as CRMP2. Posttranslational modifications have been hypothesized to contribute to the initial aggregation events that lead to SPs and NFTs. Dehydroamino acids (DHAAs) are posttranslational modifications rarely observed in humans and have not previously been reported in AD. DHAAs arise from the eliminylation of serine, threonine, or cysteine, yielding a double bond with distinct molecular geometry and reactivity. Their geometry can produce secondary structure rearrangements, such as those seen in senile plaque and neurofibrillary tangle formation, while their reactivity can cause intramolecular or intermolecular (protein-protein) crosslinking. We hypothesized that this modification might be present in protein aggregation-associated neurodegenerative disorders like AD.MethodsWe performed mass spectrometry-based bottom-up proteomics on the sarkosyl-insoluble (protein aggregate-enriched) material from ten AD brains and three age-matched controls. Identifications of DHAA-mediated crosslinked peptides were validated using both an isotopic labeling strategy and spike-in experiments employing synthetic crosslinked peptide standards. Similar findings were obtained in searches of publicly available proteomic datasets from AD and control brains.ResultsWe identified 412 sites of DHAA modification in 184 proteins, with the highest prevalence in the neurofibrillary tangle-forming proteins Tau and CRMP2. Comparison with results of previous protein aggregate interactomics studies show that proteins containing the DHAA modification are more highly associated with protein aggregates than are proteins containing any other individual posttranslational modification. We further observed 11 protein crosslinks arising from DHAAs, including three from the Tau protein. Label free quantification showed that Tau crosslinks are an order of magnitude more prevalent in AD samples than in age-matched controls.ConclusionsDehydroamino acids and their derivatives are prevalent modifications in the Alzheimer’s disease brain proteome. These modifications give rise to protein crosslinks which may contribute to protein aggregation processes.
A membrane-associated conveyor belt controls the rotational direction of the bacterial type 9 secretion system
Authors: Trivedi Abhishek , Miratsky Jacob A. , Henderson Emma C. , Singharoy Abhishek , Shrivastava Abhishek 
Published: September 2024

ABSTRACTMany bacteria utilize the type 9 secretion system (T9SS) for gliding motility, surface colonization, and pathogenesis. This dual-function motor supports both gliding motility and protein secretion, where rotation of the T9SS plays a central role. Fueled by the energy of the stored proton motive force and transmitted through the torque of membrane-anchored stator units, the rotary T9SS propels an adhesin-coated conveyor belt along the bacterial outer membrane like a molecular snowmobile, thereby enabling gliding motion. However, the mechanisms controlling the rotational direction and gliding motility of T9SS remain elusive. Shedding light on this mechanism, we find that in the gliding bacteriumFlavobacterium johnsoniae, deletion of the C-terminus of a conveyor belt protein GldJ controls, and in fact, reverses the rotational direction of T9SS from counterclockwise to clockwise thus suggesting that the interface between the conveyor belt protein GldJ and the T9SS ring protein GldK plays an important role in controlling the directionality of T9SS. Combined with MD simulation of the T9SS stator units GldLM, we suggest a ‘tri-component gearset’ model where the conveyor belt controls the rotational direction of its driver, the T9SS, thus providing adaptive sensory feedback to influence the motility of the gliding bacterium.
Distinct classes of antidepressants commonly act to shape pallidal structure and function in mice
Authors: Abe Yoshifumi , Sugiura Yuki , Maeda Rae , Taira Shu , Yoshida Keisuke , Ibi Daisuke , Hashimoto Kenji , Yagishita Sho , Tanaka Kenji F 
Published: September 2024

AbstractAntidepressants, including selective serotonin reuptake inhibitors (SSRIs), ketamine, and psilocybin, are effective for treating depression despite their distinct modes of action. We hypothesized that their underlying mechanisms of action are shared. Mice were administered escitalopram (15 mg/kg daily for 3 weeks, 21 mice), R-/S-/racemic ketamine (10 mg/kg, single injection, 21–22 mice), or psilocin (1 mg/kg, single injection, 22 mice).Electroconvulsive stimulation (9 times for 3 weeks, 12 mice) and saline were used as controls. After structural magnetic resonance imaging (MRI) of fixed brains, voxel-based morphometry was conducted to assess brain-wide volumetric changes. A single dose of ketamine or psilocin was sufficient to induce MRI-detectable volume changes. All antidepressants increased the volume in the nucleus accumbens, ventral pallidum, and external globus pallidus and decreased the volume in the mediodorsal thalamus, which is distinct from the changes observed with electroconvulsive stimulation. We identified microstructural and molecular changes using super-resolution microscopy and imaging mass spectrometry, respectively. Pallidal volumetric increases were associated with hypertrophy of striatal medium spiny neuron terminals and increased γ-aminobutyric acid (GABA) content. We experimentally addressed whether the overexpression of the vesicular GABA transporter (VGAT) reproduced these changes. The overexpression of striatal VGAT reproduced these structural changes. R-ketamine, SR-ketamine, and psilocin induced more pronounced ventral pallidum hypertrophy, and SSRIs and S-ketamine induced globus pallidus hypertrophy. We discovered shared pallidum-centered structural and molecular changes among various antidepressants, which possibly potentiate the striato-pallidial inhibition associated with antidepressant action. Our data support visualizing antidepressant responses using pallidum-centered GABA MR spectroscopy or structural MRI.
microRNA-138-5p suppresses excitatory synaptic strength at the cerebellar input layer
Authors: Delvendahl Igor , Daswani Reetu , Winterer Jochen , Germain Pierre-Luc , Uhr Nora Maria , Schratt Gerhard , Müller Martin 
Published: September 2024

AbstractMicroRNAs are small, highly conserved non-coding RNAs that negatively regulate mRNA translation and stability. In the brain, microRNAs contribute to neuronal development, synaptogenesis, and synaptic plasticity. The microRNA 138-5p (miR-138-5p) controls inhibitory synaptic transmission in the hippocampus and is highly expressed in cerebellar excitatory neurons. However, its role in cerebellar synaptic transmission remains unkwown. Here, we investigated excitatory transmission within the cerebellum in mice expressing a sponge construct that sequesters endogenous miR-138-5p. Mossy fiber stimulation-evoked excitatory postsynaptic currents (EPSCs) in granule cells were significantly larger compared with controls. Furthermore, we observed larger miniature EPSC amplitudes, suggesting increased postsynaptic AMPA receptor numbers. High-frequency train stimulations revealed enhanced short-term depression following miR-138-5p downregulation. Together with computational modelling, this suggests a negative regulation of presynaptic release probability. Overall, our results demonstrate that miR-138-5p suppresses synaptic strength through pre- and postsynaptic mechanisms, providing a powerful mechanism for tuning excitatory synaptic input into the cerebellum.
Corporate governance and financial performance: the case of English NHS hospitals
Authors: Achiro Laura Obwona , Tauringana Venancio , Alta'any Mohammad 
Published: September 2024

PurposeHospitals’ corporate governance (CG) mechanisms oversee critical operational issues and evaluate the outcomes. This paper investigates the impact of CG (i.e. board size, board independence, board expertise, board meetings, board gender diversity, CEO gender, and academic directors) on the financial performance of English National Health Service (NHS) hospitals and separately by hospital type (i.e. trusts and foundation trusts).Design/methodology/approachThe sample includes 128 NHS hospitals. The data were collected through document analysis and archival work from annual hospital reports from 2014 to 2018.FindingsThe findings indicate that board expertise, board meetings, board diversity, CEO gender, and academic directors significantly and negatively affect NHS hospitals’ financial performance. For NHS trusts, the results reveal that board expertise, board diversity, and CEO gender have a significant negative effect, while for NHS foundation trusts, only CEO gender has a significant negative impact.Originality/valueOverall, this study contributes to the literature on the healthcare system. It holds significant practical implications for hospital governance and has important implications for theories.
Impact of the Israel–Hamas conflict on financial markets of MENA region – a study on investors’ reaction
Authors: Yudaruddin Rizky , Lesmana Dadang , Yudaruddin Yanzil Azizil , Ekşi̇ İbrahim Halil , Başar Berna Doğan 
Published: September 2024

PurposeThis study aims to examine market reactions to the Israel–Hamas conflict in neighboring countries, particularly focusing on the Middle East North Africa (MENA) region.Design/methodology/approachThe study adopts an event study methodology, employing average abnormal return (AAR) and cumulative abnormal return as measures to assess market reactions. The sample for this study comprises 1,314 companies, with October 9, 2023, identified as the event day for analysis.FindingsThe results of our study indicate that countries in close proximity to Israel and Palestine encountered detrimental effects on their capital markets, as evidenced by negative responses observed across various sectors. Our analysis also reveals that countries in the midst of conflict, particularly Israel, experienced a decrease in their stock markets across various sectors, with the exception of materials and real estate. In addition, our investigation reveals disparities in market responses according to different categories of company size.Originality/valueThis research is the first to study market reactions to Israel–Hamas in the MENA region at the company level.
Wellness tourism destination loyalty formation: the role of mental health and eudaimonic well-being
Authors: Chua Bee-Lia , Kim Seongseop (Sam) , Ling Esther Sii Wei , Xu Yuchen , Ryu Hyungseo Bobby , Han Heesup 
Published: September 2024

PurposeWellness tourism is growing in importance as increasing numbers of travelers place a priority on their health and well-being by traveling. This study examined the relationships between wellness tourism destination attributes, perceived quality, perceived mental health, eudaimonic well-being, overall satisfaction and behavioral loyalty to corroborate a model explaining wellness tourism destination loyalty in Thailand.Design/methodology/approachThe conceptual model of this study was examined using a survey research design. The survey questionnaire was distributed to Chinese tourists who had previously traveled to Thailand and engaged in wellness tourism activities during their trip.FindingsThe findings revealed that healthful food choices, core facilities and staff service significantly influenced perceived quality. This perceived quality was a crucial factor in determining perceived mental health, which in turn impacted eudaimonic well-being. Overall satisfaction was directly influenced by perceived quality, perceived mental health and eudaimonic well-being. Additionally, perceived quality had a direct effect on behavioral loyalty.Practical implicationsWith the growing global interest in wellness and travel, this study offers valuable insights for tourism marketers in Thailand to enhance their wellness tourism strategies. Tourism organizations should emphasize the quality of food, facilities and staff service to attract wellness-oriented travelers.Originality/valueThis study highlights the interconnectedness of perceived quality, good mental health and eudaimonic well-being. High-quality experiences contribute to improved mental health and in turn enhance eudaimonic well-being.
Understanding underdog brand positioning effects among emerging market consumers: a moderated mediation approach
Authors: Patel Jayesh D. , Trivedi Rohit , Malhotra Svablum , Jagani Khyati 
Published: September 2024

Purpose
This study aims to explore the underdog brand biography dimensions that emerging-country consumers identify with (Study 1) and attempts to uncover the effects of these dimensions on brand affinity and purchase intention moderated by self-identity and brand trust (Study 2).

Design/methodology/approach
Study 1, using data from 359 young Indians, reveals three underlying dimensions integral to underdog brand biography in emerging markets. Study 2 uses an experimental setup with a single-factorial design among 332 young Mexican consumers to investigate the direct effects of three identified underdog brand biography dimensions on purchase intention, mediated by brand affinity and moderated by consumer self-identity and brand trust.

Findings
Study 1 reveals three dimensions underlying underdog brand biographies: unfavorable circumstances, striving in adversities and passion, and persistent will to succeed. Study 2 reveals that consumers with higher self-identity demonstrate greater purchase intentions for an underdog brand than a top dog one.

Practical implications
The results indicate that marketers can successfully use underdog narratives to influence consumer decision-making, thereby increasing brand affinity and purchase intention.

Originality/value
This study delineates the link between different dimensions of underdog brand biographies with brand affinity and purchase intention in emerging countries and builds on the understanding of the moderating role played by self-identity and brand trust.
To acknowledge or conceal: an exploratory study on designers' self-determination factors and attitudes toward artificial intelligence participation in their works
Authors: Jiang Qianling , Qian Jue , Zang Yong 
Published: September 2024

PurposeThe rapid development and widespread application of artificial intelligence tools have raised concerns about how designers are embracing these technologies. This study investigates the factors influencing designers' behavioral intention to use and disclose the use of generative artificial intelligence.Design/methodology/approachA quantitative research approach was employed, designing a structured questionnaire based on Self-Determination Theory to assess the impact of various psychological and social dimensions. The questionnaire included dimensions such as autonomy, competence, relatedness, social influence, value fit and social innovativeness. A Partial Least Squares Structural Equation Modeling analysis was conducted on 309 valid responses from diverse design fields.FindingsCompetence and relatedness are significant factors influencing designers' continuance intention to use generative artificial intelligence. Although autonomy does not significantly affect continuance intention, it plays a crucial role in the decision to disclose artificial intelligence participation. Social influence and value fit significantly shape autonomy, competence and relatedness, while the impact of social innovativeness is relatively limited.Originality/valueThis study clarifies the factors influencing designers' continuance intention and disclosure of generative artificial intelligence tools from both individual and social dimensions, enhancing the understanding of the relationship between designers and generative artificial intelligence tools. It provides valuable insights for the development of artificial intelligence technology and the future trends in the design industry, offering significant theoretical and practical value.