bluuebunny/crossref_metadata_2025_split huggingface dataset:
NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency
Authors: Cendrowski Jaroslaw , Wrobel Marta , Mazur Michal , Jary Bartosz , Wang Surui , Korostynski Michal , Dziewulska Anna , Rohm Maria , Dobrzyn Agnieszka , Zeigerer Anja , Miaczynska Marta 
Published: June 2024

ABSTRACTEndosomal Sorting Complexes Required for Transport (ESCRTs) are crucial for delivering membrane receptors or intracellular organelles for lysosomal degradation. Yet, how ESCRT dysfunction affects cell metabolism remained elusive. To address this, we analyzed transcriptomes of cells lacking TSG101 or VPS28 proteins, components of ESCRT-I subcomplex. ESCRT-I deficiency reduced the expression of genes encoding enzymes involved in oxidation of fatty acids and amino acids, and increased the expression of genes encoding glycolytic enzymes. Although depletion of ESCRT-I components did not impair mitochondrial biogenesis and ATP-linked respiration it caused intracellular accumulation of lipids and increased lactate production, hallmarks of aerobic glycolysis. Mechanistically, the observed transcriptional reprogramming towards glycolysis in the absence of ESCRT-I occurred due to activation of the canonical NFκB and JNK signaling pathways. Moreover, inhibiting lysosomal activity phenocopied the altered expression of metabolic genes and lipid homeostasis observed for ESCRT-I deficiency, indicating that ESCRT-I restricts glycolysis by mediating lysosomal degradation.
Functional characterization of pathway inhibitors for the ubiquitin-proteasome system (UPS) as tool compounds for CRBN and VHL-mediated targeted protein degradation
Authors: Schwalm Martin P. , Menge Amelie , Elson Lewis , Greco Francesco A. , Robers Matthew B. , Müller Susanne , Knapp Stefan 
Published: June 2024

SummarySmall molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) or molecular glues are new modalities for drug development and important tools for target validation. Both modalities recruit an E3 ubiquitin ligase to a protein of interest (POI) either via two independent, but linked ligands (PROTACs) or through binding of a small molecule that alters the E3 binding surface to recruit a neo-substrate (molecular glues). If optimized appropriately, both modalities result in the degradation of the POI. Due to the complexity of the induced multistep degradation process, controls for degrader evaluation are critical and they are commonly used in the literature. However, comparative studies and evaluation of cellular potencies of these control compounds and their appropriate uses have not been published so far. Additionally, the high diversity of mechanisms requires diverse small molecule controls to ensure appropriate inhibition of the investigated system while keeping potential cellular toxicity and unintended effects on cellular pathways as low as possible. Here, we scrutinized a diverse set of ubiquitin pathway inhibitors and evaluated their potency and utility within the CRBN and VHL mediated POI degradation pathway. We used the HiBiT system to measure the levels of target rescue after treatment with control compounds. Additionally, cell health was investigated using a multiplex high content assay. This assay panel allows us to determine non-toxic effective concentrations for control experiments and to perform rescue experiments in the absence of cellular toxicity, which has a profound effect on target degradation by ubiquitin-dependent and -independent pathways.
Dysregulated Skeletal Muscle Myosin Super-relaxation and Energetics in Type II Diabetes
Authors: Lewis Christopher T. A. , Moreno-Justicia Roger , Savoure Lola , Calvo Enrique , Bak Agata , Laitila Jenni , Seaborne Robert A.E. , Larsen Steen , Iwamoto Hiroyuki , Cefis Marina , Morais Jose A. , Gouspillou Gilles , Alegre-Cebollada Jorge , Hawke Thomas J. , Vazquez Jesús , Adrover Miquel , Marcangeli Vincent , Deshmukh Atul S. , Ochala Julien 
Published: June 2024

AbstractDisrupted energy balance is critical for the onset and development of Type II diabetes. The exact underlying metabolic mechanisms remain incomplete but skeletal muscle is thought to play an important pathogenic role. As the super-relaxed state of its most abundant protein, myosin, regulates cellular energetics, here, we aimed to investigate whether it is altered in patients with type II diabetes. For that, we used vastus lateralis biopsy specimens (obtained from patients with type II diabetes and matched controls) and run a combination of structural and functional assays consisting of loaded Mant-ATP chase experiments, X-ray diffraction and LC-MS/MS proteomics in isolated muscle fibres. Our studies revealed a greater muscle myosin super-relaxation and decreased cellular ATP demand in patients than controls. Subsequent proteomic analyses indicated that these (mal)adaptations likely originated from remodeled sarcomeric proteins and greater myosin glycation levels in patients than controls. Overall, our findings emphasize a complex molecular dysregulation of myosin super-relaxed state and energy consumption in type II diabetes. Ultimately, pharmacological targeting of myosin could benefit skeletal muscle and whole-body metabolic health through the enhancement of ATP consumption.Significance StatementMyosin super-relaxation, essential for the regulation of skeletal muscle metabolic rate, is disrupted in type II diabetes due to protein hyper-glycation. As a consequence, myosin ATP demand is significantly lowered. Overall, our findings provide a strong rationale for the use of activators of myosin ATPase to enhance basal energy expenditure in type II diabetes.
The effect of a dominant kinase-deadCsf1rmutation associated with adult-onset leukoencephalopathy on brain development and neuropathology
Authors: Stables Jennifer , Pal Reiss , Bradford Barry M. , Carter-Cusack Dylan , Taylor Isis , Pridans Clare , Khan Nemat , Woodruff Trent , Irvine Katharine M. , Summers Kim M. , Mabbott Neil A. , Hume David A. 
Published: June 2024

AbstractAmino acid substitutions in the kinase domain of the humanCSF1Rprotein are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (Glu631Lys; E631K) in the mouseCsf1rlocus. Previous analysis demonstrated that heterozygous mutation (Csf1rE631K/+) had a dominant inhibitory effect on CSF1R signalingin vitroandin vivobut did not recapitulate the pathology of the human disease. We speculated that leukoencephalopathy in humans requires an environmental trigger and/or epistatic interaction with common neurodegenerative disease-associated alleles. Here we examine the impact of heterozygousCsf1rmutation on microglial phenotype, normal postnatal brain development, age-related changes in gene expression and on two distinct pathologies in which microgliosis is a prominent feature, prion disease and experimental autoimmune encephalitis (EAE). The heterozygousCsf1rE631K/+mutation reduced microglial abundance and the expression of microglial-associated transcripts relative to wild-type controls at 12 weeks and 43 weeks of age but had no selective effect on homeostatic markers such asP2ry12. An epistatic interaction was demonstrated betweenCsf1rE631K/+andCxc3r1EGFP/+genotypes leading to dysregulated microglial and neuronal gene expression in both hippocampus and striatum. HeterozygousCsf1rE631Kmutation reduced the microgliosis associated with both diseases. There was no significant impact on disease severity or progression in prion disease. In EAE, induced expression of inflammation-associated transcripts in the hippocampus and striatum was suppressed in parallel with microglia-specific transcripts, but spinal cord demyelination was exacerbated. The results support a dominant-negative model of CSF1R-associated leukoencephalopathy and likely contributions of an environmental trigger and/or genetic background to neuropathology.
Decoding movie content from neuronal population activity in the human medial temporal lobe
Authors: Gerken Franziska , Darcher Alana , Gonçalves Pedro J , Rapp Rachel , Elezi Ismail , Niediek Johannes , Kehl Marcel S , Reber Thomas P , Liebe Stefanie , Macke Jakob H , Mormann Florian , Leal-Taixé Laura 
Published: June 2024

AbstractNeurons of the medial temporal lobe (MTL) form the basis of semantic representation in the human brain. While known to contain category-selective cells, it is unclear how the MTL processes naturalistic, dynamic stimuli. We studied 2286 neurons recorded from the hippocampus, parahippocampal cortex, amygdala, and entorhinal cortex of 29 intracranially-implanted patients during a full-length movie. While few neurons responded preferentially to semantic features, we could reliably predict the presence of characters, location, and visual transitions from the neuronal populations using a recurrent neural network. We show that decoding performance differs across regions based on the feature category, and that the performance is driven by feature-selective single neurons when decoding visual transitions such as camera cuts. These findings suggest that semantic representation in the MTL varies based on semantic category, with decoding information embedded in specific subsets of neurons for event-related features or distributed across the entire population for character and location-related features.
Mapping the evolution of financial inclusion: a retrospective overview using bibliometric analysis
Authors: Suryavanshi Urvashi , Chaudhry Rishi , Arora Meenal , Mittal Amit 
Published: June 2024

Purpose
The purpose of this paper is to analyze the existing literature in the domain of financial inclusion and emphasizing forthcoming trends. It examines recent literature while assessing the geographical distribution, identifying well-known authors, publications, journals and keyword occurrences.

Design/methodology/approach
Based on a scientific search technique, bibliometric analysis in the field of financial inclusion was carried out on a sample of 2,125 Scopus documents for the years 2004–2022. A VOS viewer was used in the study as a tool for performance evaluation and analysis of the science mapping.

Findings
The bibliometric analysis illustrates that India and the USA are dominating in financial inclusion field with significant contributions. The most well-known authors were Ghosh, S. and Munene, J.C. and International Journal of Social Economics was considered as the best journal. Finally, six prominent clusters were identified through keyword analysis. The major themes revolve around digitalization, economic development, demographic and geographic factors and financial literacy.

Practical implications
The research helps in providing information for formulating financial inclusion policies for RBI and Government of India. A comprehensive literature assessment is useful for future scholars to develop a solid conceptual framework. This research would help practitioners to formulate strategies for rural population to enhance their earnings, investments and money.

Originality/value
This study can supply data to describe the framework of earlier financial inclusion studies and provides potential directions for future research.
Empirical modeling of stress concentration factors using artificial neural networks for fatigue design of tubular T-joint under in-plane and out-of-Plane bending moments
Authors: Rasul Adnan , Karuppanan Saravanan , Perumal Veeradasan , Ovinis Mark , Iqbal Mohsin , Alam Khurshid 
Published: June 2024

PurposeStress concentration factors (SCFs) are commonly used to assess the fatigue life of tubular T-joints in offshore structures. SCFs are usually estimated from parametric equations derived from experimental data and finite element analysis (FEA). However, these equations provide the SCF at the crown and saddle points of tubular T-joints only, while peak SCF might occur anywhere along the brace. Using the SCF at the crown and saddle can lead to inaccurate hotspot stress and fatigue life estimates. There are no equations available for calculating the SCF along the T-joint's brace axis under in-plane and out-of-plane bending moments.Design/methodology/approachIn this work, parametric equations for estimating SCFs are developed based on the training weights and biases of an artificial neural network (ANN), as ANNs are capable of representing complex correlations. 1,250 finite element simulations for tubular T-joints with varying dimensions subjected to in-plane bending moments and out-of-plane bending moments were conducted to obtain the corresponding SCFs for training the ANN.FindingsThe ANN was subsequently used to obtain equations to calculate the SCFs based on dimensionless parameters (α, β, γ and τ). The equations can predict the SCF around the T-joint's brace axis with an error of less than 8% and a root mean square error (RMSE) of less than 0.05.Originality/valueAccurate SCF estimation for determining the fatigue life of offshore structures reduces the risks associated with fatigue failure while ensuring their durability and dependability. The current study provides a systematic approach for calculating the stress distribution at the weld toe and SCF in T-joints using FEA and ANN, as ANNs are better at approximating complex phenomena than typical data fitting techniques. Having a database of parametric equations enables fast estimation of SCFs, as opposed to costly testing and time-consuming FEA.
Protection of traditional villages in China: a review on the development process and policy evolution
Authors: Jing Feng , Ramele Ramli Rohaslinda , Nasrudin Na'asah 
Published: June 2024

PurposeThis study discusses the protection of traditional villages and understand the role, policy environment and characteristics of traditional village protection. This study also constructs an analytical framework of “historical timing - policy orientation” to study the development process and policy evolution of traditional village protection in China.Design/methodology/approachThis study selects the policy documents related to traditional village protection since 1980 as the research samples to explore the origin and evolution of traditional village protection in China. Then, the paper systematically combs the temporal evolution of the policy theme and orientation at each stage, which would provide a reference direction for the protection and development of traditional villages.FindingsThe interpretation of traditional village protection and its institutional background can be divided into three stages: relying on the protection system of historical and cultural towns and villages (1982–2012) and the stage of construction and improvement of traditional villages protection system (2012–2017). After 2017, traditional village protection entered a new rural revitalization journey.Research limitations/implicationsThis study is limited to: documents issued from 1982 to the end of 2022; Central Committee of the Communist Party of China, the State Council, and central ministries and administrations directly governing the protection of traditional villages; policies that can directly reflect the central government’s attitude towards protecting traditional villages; and excluding the documents for some particular regions and particular problems.Originality/valueThis study fulfills as the guidance of traditional village protection and development in different periods.
Navigating uncertainty: a study of the S&P GCC composite index’s connectedness during times of crises
Authors: Alshater Muneer M. , El Khoury Rim , Almansour Bashar 
Published: June 2024

Purpose
This study aims to investigate the dynamics of return connectedness of the Standard & Poor’s (S&P) Gulf Cooperation Council (GCC) composite index with five regional equity indices, three global equity indices and other different asset classes during the COVID-19 pandemic period.

Design/methodology/approach
This study uses daily data spanning from January 2, 2018, to December 23, 2021. A subsample analysis is conducted to determine the role of uncertainty in modifying the connectedness structure during the ongoing pandemic period.

Findings
The results of this study show that the nature of connectedness is time-frequent, with clear evidence for a higher level of connectedness during stress periods, especially after the onset of the pandemic. The GCC index is found to be a net receiver of shocks to other assets, with an increase in magnitude during the COVID period.

Research limitations/implications
This study is limited by the use of only daily data, and future research could consider using higher frequency data.

Practical implications
The results of this study confirm the disturbing effects of the pandemic on the GCC index and its connectedness with other assets, which matters for policymakers and investors.

Originality/value
This study provides new insights into the dynamics of return connectedness of the GCC index with other assets during the COVID-19 pandemic period, which has not been previously explored.
Purpose is the new branding: understanding conscientious purpose-driven marketing and its impact on brand outcomes
Authors: Fernandes Teresa , Guzman Francisco , Mota Mafalda 
Published: June 2024

PurposeConsumers increasingly expect brands to have a social purpose. Yet, guidelines on how to effectively engage in conscientious purpose-driven branding are lacking. This study aims to better understand what the key drivers of a successful conscientious purpose-driven branding strategy are and what is its impact on key brand outcomes.Design/methodology/approachData was gathered using a self-administered survey, answered by 670 young adults belonging to generations Y and Z. The study integrates in a single moderated-mediation model, tested using partial least squares structural equation modelling, the joint effects of cause–brand–consumer congruences, cause-brand authenticity and brand image, on consumers’ intention to purchase and recommend the brand.FindingsConsumer-brand congruence mediates the path from cause-brand congruence and authenticity to brand image, which in turn impacts purchase and recommendation intentions, with authenticity playing a dominant role. Moreover, for consumers highly congruent with the cause/purpose, the direct effect of cause-brand congruence on brand image becomes non-significant and only works through consumer-brand congruence.Originality/valueTheoretically, this study contributes to a better understanding of how and when conscientious purpose-driven branding can be effective. Its findings further advance prior research, by providing an alternative path anchored on cause-brand authenticity to explain positive effects of conscientious purpose-driven marketing on brand outcomes. Moreover, it challenges prior assumptions regarding the impact of consumer-cause congruence on the effectiveness of these strategies. Finally, it highlights that cause-consumer and brand-consumer congruencies also play a role, offering an integrated, triadic view of conscientious purpose-driven branding strategies. Managerially, it provides insights to brand managers wishing to successfully implement these strategies and better understand the role of brands as “purpose-driven entities”.
Reorganization of motor network in patients with Parkinson's disease after deep brain stimulation
Authors: Luo Bei , Chang Lei , Qiu Chang , Dong Wenwen , Zhao Liang , Lu Yue , Sun Jian , Yan Jiuqi , Wei Xiang , Yan Jun , Zhang Wenbin 
Published: June 2024

AbstractAimsParkinson's disease (PD) patients experience improvement in motor symptoms after deep brain stimulation (DBS) and before initiating stimulation. This is called the microlesion effect. However, the mechanism remains unclear. The study aims to comprehensively explore the changes in functional connectivity (FC) patterns in movement‐related brain regions in PD patients during the microlesion phase through seed‐based FC analysis.MethodsThe study collected the resting functional magnetic resonance imaging data of 49 PD patients before and after DBS surgery (off stimulation). The cortical and subcortical areas related to motor function were selected for seed‐based FC analysis. Meanwhile, their relationship with the motor scale was investigated.ResultsThe motor‐related brain regions were selected as the seed point, and we observed various FC declines within the motor network brain regions. These declines were primarily in the left middle temporal gyrus, bilateral middle frontal gyrus, right supplementary motor area, left precentral gyrus, left postcentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus after DBS.ConclusionThe movement‐related network was extensively reorganized during the microlesion period. The study provided new information on enhancing motor function from the network level post‐DBS.
Rethinking Subjectification: On the Limits of Biesta's Educational Theory
Authors: Thompson Andrew 
Published: June 2024

AbstractIn this article, Andrew Thompson explores the tension between Gert Biesta's concept of educational purpose and education's historical function. For Biesta, the purpose of education consists of three overlapping spheres: qualification, socialization, and subjectification. While scholars have devoted a great deal of attention to Biesta's notion of subjectification, there is not enough consideration of his treatment of socialization and its limits on human freedom. Here, Thompson examines the historical role of socialization as it relates to the cultivation of self‐reflecting and self‐governing citizens through a process Ian Hunter describes as pastoral pedagogy. Both Biesta and Hunter critique essentialist notions of subjectivity, noting that critical pedagogy in both liberal and Marxian iterations has relied upon a metaphysics informed by Kantian moral definition in which the subject must freely exercise rational autonomy toward self‐realization. While Biesta suggests redefining the subject, Hunter dismisses any attempt at redefinition as irrelevant since the school's historical process of moral development is inevitably linked to the antiquated liberal ideal. In Hunter's view, all attempts to escape the school's moral teleology inexorably employ a pedagogy that is based on the moral ideal its critics wish to eliminate. This article illustrates the agonism inherent in Biesta's concept of educational purpose and explores the role of the theorist as the expression of a particular moral self that informs the ideal persona of the teacher.