bluuebunny/crossref_metadata_2025_split huggingface dataset:
An anti-amyloidogenic approach to specifically block memory consolidation in mice for therapeutic intervention
Authors: López-García Paula , McGreevy Kerry R. , Vaquero Maria Eugenia , Ramírez de Mingo Daniel , Pallé Anna , Popiel Helena Akiko , Santi Andrea , Nagai Yoshitaka , Trejo José Luis , Carrión-Vázquez Mariano 
Published: January 2025

AbstractPost-traumatic stress disorder (PTSD) is a mental health disorder triggered by the exposure to a traumatic event, which manifests with anguish, intrusive memories, and negative mood changes. So far, there is no efficient treatment for PTSD other than symptomatic palliative care. However, the cytoplasmic polyadenylation element binding protein-3 (CPEB3) has been recently associated to a potential risk gene for PTSD. Considering that CPEB3 protein is a functional amyloid whose importance for long-term memory consolidation in mammals is well established, we propose the active (amyloid) state of CPEB3 as a promising therapeutic target to block the consolidation of traumatic memories through by the anti-amyloidogenic polyglutamine binding peptide 1 (QBP1).Here we report a preclinical development in mice of this pharmacological treatment for PTSD based on the action of the QBP1 peptide. We first characterized the human CPEB3 (hCPEB3) proteinin vitro, showing how its amyloid aggregation is inhibited by the active core of QBP1 (QBP1-M8) without affecting other self-assembly processes such as phase separation. Then, we generated and characterized a novel transgenic mouse that constitutively expresses QBP1 in tandem (TgQBP1). TgQBP1 mice have shown that the consolidation of simple learning is impaired after 24 h for both hippocampal-dependent and aversive memories and that it is limited to new learned memories and has no effect on short-term memory. Furthermore, fear induced anxiety was reduced in comparison to WT mice, suggesting that PTSD-like symptoms are also being ameliorated. Intriguingly, we found that aversive memories seem to be more strongly affected in younger mice. Finally, the analysis of CPEB3 amyloid presence in hippocampal extracted samples showed a correlative decrease in murine CPEB3 oligomerization in the TgQBP1 mice. Taking together, these results strongly suggest that the amyloidogenic blockage of CPEB3 by QBP1 peptide is a potential drug for the prevention and treatment of PTSD.
Emergence of Lignin-Carbohydrate Interactions During Plant Stem Maturation Visualized by Solid-State NMR
Authors: Xiao Peng , Pfaff Sarah A. , Zhao Wancheng , Debnath Debkumar , Liu Chang-Jun , Cosgrove Daniel J. , Wang Tuo 
Published: January 2025

ABSTRACTLignification waterproofs and strengthens the secondary plant cell wall, while increasing the energy cost associated with releasing sugars for biofuel production. The physical association between lignin and the carbohydrate scaffold that accommodates lignin polymerization, as well as the temporally distinct roles of different lignin units and carbohydrate partners during lignification, remain largely unclear. Here we map the lignin-carbohydrate interactions by solid-state NMR in13C-labeledArabidopsis inflorescence stems as secondary cell walls are formed. Analysis includes wild-type and two mutants that either selectively or globally disrupt lignin biosynthesis. Mature cell walls in the basal regions of older stems are enriched in S-lignin and carbohydrate-lignin interactions. Acetylated xylan is the dominant mediator of interactions with S-lignin, while methylated pectin unexpectedly interacts with G-lignin during early-stage lignification. The critical role of S-lignin in stabilizing carbohydrate-lignin interface is emphasized by the weak lignin-carbohydrate interactions and compromised mechanical properties of a low-Sfah1mutant, whereas theref3mutant, with low overall lignin content but a higher S/G ratio, remained unaffected. These findings demonstrate that the molecular mixing pattern, rather than lignin content, is a key determinant of the structure and properties of lignocellulosic materials.
R2TP-like Quaternary Chaperones: a comprehensive overview to understand the dynamic R2SP complex
Authors: Santo Paulo E. , Chagot Marie-Eve , Gizardin-Fredon Hugo , Ley Marie , Chenuel Thomas , Deslignière Evolène , Plassart Laura , Paiva Ana C. F. , Sousa Pedro M. F. , Bertrand Edouard , Charpentier Bruno , Verheggen Céline , Quinternet Marc , Meyer Philippe , Bandeiras Tiago M. , Cianférani Sarah , Plisson-Chastang Célia , Manival Xavier 
Published: January 2025

AbstractThe human R2SP complex belongs to the R2TP-like quaternary chaperone family and consists of RUVBL1, RUVBL2, SPAG1 and PIH1D2. R2SP is crucial for the correct assembly of motile cilia (SPAG1 null mutations cause Primary Ciliary Dyskinesia) and the organization of the synaptic zone. RUVBL1/2 ATPases are the powerhouse of this molecular machinery, while SPAG1 and PIH1D2 would be adaptors that interact with specific clients to promote their quaternary assembly. Despite these functional data, little is known about the structure of R2SP and the precise mode of action of these R2TP-like complexes. We have combined biochemical and structural approaches (NMR, structural mass spectrometry and cryo-EM) to investigate the 3D organization of the human R2SP complex, its mode of assembly and ATPase activity. Our study reveals a three-dimensional structure similar to that of the canonical R2TP complex, but also highlights differences in the mode of action of its RUVBL1/2 ATPase core as well as the binding of its adaptors SPAG1 and PIH1D2.
Resilience to Endoplasmic Reticulum Stress Mitigates Calcium-Dependent Membrane Hyperexcitability Underlying Late Disease Onset in SCA6
Authors: Huang Haoran , Charron Taylor L. , Fu Min , Dunn Miranda , Jones Deborah M. , Kumar Praveen , Kulkarni Ashwinikumar , Konopka Genevieve , Shakkottai Vikram G. 
Published: January 2025

AbstractAn enduring puzzle in many inherited neurological disorders is the late onset of symptoms despite expression of function-impairing mutant protein early in life. We examined the basis for onset of impairment in Spinocerebellar ataxia type 6 (SCA6), a canonical late-onset neurodegenerative ataxia which results from a polyglutamine expansion in the voltage gated calcium channel, Cav2.1. Cerebellar Purkinje cell spiking abnormalities are seen concurrent with motor impairment in SCA6 mice but the basis for these changes in spiking is unknown. We identify endoplasmic reticulum (ER) calcium depletion as the cause for Purkinje cell spiking abnormalities and that the impairments in Purkinje cell spiking are unrelated to Cav2.1 ion-flux function. Further, intact inhibitory neurotransmission in the cerebellar cortex is necessary for Purkinje neurons to exhibit spiking abnormalities in SCA6 mice. Based on serial cerebellar transcriptome analysis, we define a mechanism of disease that is related to ER stress. Further, our studies support a model whereby proteotoxicity from misfolded mutant Cav2.1 is mitigated by a HSP90-dependent unfolded protein response (UPR) and that age-related breakdown of this response causes motor dysfunction and aberrant Purkinje cell spiking. Redundant pathways of the UPR mediate this resilience to ER stress. These studies elucidate a mechanism of resilience connecting aberrant proteostasis and calcium-dependent intrinsic membrane hyperexcitability to explain delayed disease onset more widely in age-dependent neurodegenerative disease.Significance StatementAdvancing age is the single most important risk factor for neurodegenerative disease. Understanding how age intersects with genetic risk is therefore a critical challenge for neurodegenerative disease research. SCA6, a canonical late-onset degenerative cerebellar ataxia, results from a polyQ expansion in the voltage gated calcium channel, Cav2.1, encoded byCACNA1A. We define a mechanism of disease in SCA6 that is related to ER stress and unrelated to impaired calcium flux function of Cav2.1. Age-related decompensation of a HSP90-dependent unfolded protein response leads to disease onset. Mutant Cav2.1 misfolding as the basis for disease in SCA6 provides insight into a novel role for channelopathies to behave as proteinopathies and helps understand resilience to proteotoxicity more widely in adult-onset neurodegenerative disease.
Thalamic oscillations distinguish natural states of consciousness in humans
Authors: Chowdhury Aditya , Kaufmann Elisabeth , Schreiner Thomas , Koeglsperger Thomas , Mehrkens Jan-Hinnerk , Remi Jan , Vollmar Christian , Staudigl Tobias 
Published: January 2025

AbstractNatural states of consciousness are thought to be regulated by deep brain structures such as the thalamus. However, very little is known about the underlying electrophysiology in humans. Using a rare opportunity to directly record from the human thalamus, we identify a hitherto- unreported brain-state-specific oscillation. We find that the oscillation is present only during Rapid Eye Movement (REM) sleep and wakefulness, while being entirely absent during Non- REM sleep. The oscillation further distinguishes REM sleep microstates, co-occurring with bursts of eye movements, and is specific to the Central Thalamus, a structure implicated in causing global brain state transitions. The discovery of a distinct oscillatory signature in the Central Thalamus that distinguishes conscious states opens up avenues to further investigate thalamic contributions to human consciousness and refine interventions to treat disorders of consciousness.
Astrocytic-supplied cholesterol drives synaptic gene expression programs in developing neurons and downstream astrocytic transcriptional programs
Authors: Vartiainen Emilia , Liyanage Dhara , Mazureac Illinca , Battaglia Rachel A. , Tegtmeyer Matthew , Xu He Jax , Räsänen Noora , Sealock Julia , McCarroll Steven , Nehme Ralda , Pietiläinen Olli 
Published: January 2025

AbstractAstrocytes participate in neuronal synaptic programs that are enriched for genetic associations in schizophrenia and autism spectrum disorders (ASD). To better understand how these co-regulated cellular programs are induced during early neuronal development, we studied astrocytes and iPSC-derived neurons in co-cultures and mono-cultures at 16 time points spanning 0.5 hours to 8 days. We found that upregulation in astrocytes of genes involved in cholesterol biosynthesis preceded the activation of synaptic gene programs in neurons and upregulation of the astrocyticNrxn1. Neuronal knockdown of key cholesterol receptors led to downregulation of neuronal synaptic genes and induced a robust transcriptional response in the astrocytes, including further upregulation ofNrxn1. This suggests that astrocyte-supplied cholesterol drives these neuronal changes and that bi-directional signalling is occuring. The genes upregulated in neurons were enriched for deleterious variants in schizophrenia and neurodevelopmental disorders, suggesting that their pathogenic effect may be, in part, mediated by reduced buffering capacity for changes in the astrocyte cholesterol supply to neurons. These findings highlight the critical role of astrocyte-neuron interactions in psychiatric and neurodevelopmental disorders, particularly in relation to lipid metabolism and synaptic plasticity.
The relationship between the digital economy and economic growth in Egypt: in a post-COVID-19 world
Authors: Alsebai Maha Mohamed 
Published: January 2025

PurposeOur study aimed to verify the role of the digital economy in economic growth in Egypt and the availability of the technological capabilities of the business sector for digital transformation, based on the negative impact of the epidemic on all economic sectors in the world in general and Egypt in particular.Design/methodology/approachThis was verified based on the standard Error correction package modeling (VECM) study and analysis using Xlstat 2023 and EViews 10.FindingsThe results of the study conducted during the period (1996–2022) showed that there is a co-integration relationship in the short and long term between the impact of the digital economy and economic growth. We found a positive, statistically significant relationship between the variables of mobile phone subscriptions and Internet use that had a strong positive effect. At the same time, trade openness hurt economic growth in the short term. In the long run, both mobile phone subscriptions and trade openness had a significant positive effect, and the speed of adjustment toward equilibrium was very severe, estimated at 4.7 years (1/0.21).Research limitations/implicationsThe work is limited to the economies of Egypt, which is part of Africa. We suggest conducting further research on evidence from other emerging and developed economies.Practical implicationsThe results are of great importance to policymakers in Egypt as an African country, as the estimation results were positive between the digital economy and economic growth in the Egyptian economy, and this is consistent with the endogenous growth model of economic growth, which assumes that knowledge is the main driver of economic growth.Social implicationsThe paper documents the importance of the digital economy in boosting economic growth, which impacts social life more than the traditional digital economy, especially in times of crisis.Originality/valueBased on the existing literature, this paper identified various research gaps. First, no consensus has been reached on the concept of the digital economy, and its index system is inadequate. While existing literature concentrates on examining the influence of ICT on economic development in terms of the number of Internet users, fixed broadband Internet users and mobile subscribers. These measures cannot adequately capture the broader implications of the digital economy. Furthermore, research has largely investigated the significance of digitalization in economic development and reached ambiguous conclusions.
From theory to practice: evaluating success factors of adaptive reuse through a case study
Authors: Vafaie Fatemeh , Remøy Hilde , Gruis Vincent 
Published: January 2025

PurposeThis study assesses the success of a real project in practice, using identified success factors from recent systematic literature. It investigates how theoretical insights translate into real-world outcomes by answering the question: “How do success factors identified in existing literature contribute to the success of a real-world adaptive reuse project?”.Design/methodology/approachThis research utilizes a case study methodology to explore the adaptive reuse phenomenon through the lens of the Fenix I in the Netherlands. Three comprehensive semi-structured interviews with key decision-makers provide insights into experiences, challenges, and ultimately the evaluation of success factors in practice. Data analysis involves deductive coding, systematically organizing success factors into ten categories derived from the literature, to implement the analysis and align with the research objectives.FindingsThe results demonstrate the application of a majority of success factors identified in literature within the case study. This study reveals differences in the levels of significance among these factors, their categorization and their existence, particularly between listed and non-listed heritage buildings. Moreover, it shows the remarkable impact of public-private collaboration from the early stages of decision-making through project implementation. The study confirms that a successful real-world project addresses a significant proportion of the success factors identified in the literature.Originality/valueThis research facilitates the decision-making process for stakeholders and practitioners in adaptive reuse projects, aiming to foster the development of more successful initiatives in this field.
The impact of green finance and FinTech mechanisms on financial stability: evidence from advanced and emerging economies
Authors: Kashif Muhammad , Pinglu Chen , Ullah Atta , Qian Ningyu 
Published: January 2025

PurposeThis study aims to examine the dynamic effect of FinTech on financial stability, with the moderating role of green finance (GF), its dimensions and mechanisms in the context of the spillover effects of the COVID-19 shock. This study used balanced panel data from 148 countries, including 76 developed and 72 emerging nations, from 2005 to 2022.Design/methodology/approachThe research utilized the dynamic two-step system (GMM), and robustness was performed with the bootstrapped panel quantile regression.FindingsThe findings reveal that FinTech significantly affects financial stability across the entire sample. The overall composite of GF boosts financial stability by improving financial soundness. The GF dimensions, such as environmental, resource and financial, positively influence FS, while the GF economic dimension hurts FS. The moderating role and all interaction terms of GF dimensions with FinTech contribute positively and significantly to FS. While the interaction term GF resources with FinTech negatively impacts FS, indicating that countries should utilize resources more efficiently. Additionally, the COVID-19 spillover effect negatively influences FS across all samples. In advanced countries, FinTech and green finance positively affect FS. In emerging countries, green finance (except for the resource dimension) and FinTech interactions enhance financial stability, (except for the environmental dimension), leading to environmental hazards from their highly intensive industrial carbon policies.Practical implicationsThe findings suggest that policymakers should prioritize promoting the adoption of initiatives related to FinTech and green finance by integrating sustainable transition finance policy frameworks to maintain stability and foster low-carbon economies for a sustainable future.Social implicationsImproved financial stability has more significant social effects, such as better investment instruments, confidence and economic growth. Policymakers can leverage these findings to establish resilient financial ecosystems, fostering sustainable economic development and decreasing the risk of financial crises.Originality/valueThis study offers novel insights into how FinTech and multi-dimensional green finance effect financial stability in advanced and emerging nations. It provides unique insights into context-specific dynamics and enhances the literature on financial stability.
A sector in crisis? Insights from how English higher education apprenticeships are weathering the storm
Authors: Power-Mason Phil , Charlton Helen , Walker-Martin Francesca , Bloomfield Sarah 
Published: January 2025

PurposeThis viewpoint explores strategic lessons for wider higher education (HE) practices from university business and management apprenticeships in England. The paper highlights parallels between the challenges in apprenticeships and those confronting HE leaders and managers, especially regarding rising regulatory pressures, financial constraints and the need for innovation. The authors present how collaboration and adaptive practices from university apprenticeships might inform broader institutional approaches.Design/methodology/approachThe paper draws on autoethnographic experiences of business and management apprenticeship leaders to characterise the current state of the HE sector. Drawing together successful collaborative apprenticeship practices, the authors narrate how their own interactions have supported innovation in the face of resource constraints, regulatory compliance and a complex stakeholder context.FindingsIntense regulatory scrutiny and resource limitations have driven innovation and collaboration within business school apprenticeships, which could offer valuable strategies for the wider HE sector. Insights include enhanced personalised student support, proactive progress monitoring, and effective partnership. Collaborative approaches developed amongst apprenticeship providers have driven continuous improvement, highlighting potential benefits to traditional HE programmes of cross-institutional collaboration and the adoption of new practices in response to rapidly changing conditions.Originality/valueContributing to the discourse on HE resilience, the authors reflect on how innovations within HE apprenticeship practice offer potential solutions to wider challenges. The paper emphasises that addressing current and future challenges in the UK HE context requires shifting from competitive isolation to cross-institutional collaboration and from top-down to bottom-up innovation.
Decision rights partitioning and sharing platform performance: a combination of cluster and configurational analyses
Authors: Shao Feifei , Wang Nianxin , Wan Xing 
Published: January 2025

PurposeResearch on decision rights partitioning and its impact on platform performance has predominantly focused on single rights, leading to inconclusive results. This study is driven by a more nuanced objective of exploring diverse governance models that can enhance the performance of sharing platforms across different contexts. Rather than delegating single decision right to users, this approach partitions several essential decision rights concurrently throughout the transaction process. By examining the complex relationships between multiple decision rights partitioning and platform performance, this study identifies and explains suitable governance models that are tailored to specific contextual factors for improving the performance of sharing platforms.Design/methodology/approachCollecting data from 60 sharing platforms in China, this study employs a combination of cluster and configuration analyses to address research questions.FindingsThe study explores three strategic decision rights partitioning modes widely adopted by sharing platforms. It further identifies four governance models for sharing platforms, which are termed as conservative seller model, conservative buyer model, aggressive seller model and aggressive buyer model, related to certain contextual factors.Originality/valueIn addressing platform governance as key to sharing platform success, the study contributes to the literature by investigating how multiple-rights partitioning portfolios and strategic differentiation in decision rights partitioning can enhance platform performance.