bluuebunny/crossref_metadata_2025_split huggingface dataset:
The unconventional Myosin-1C augments endothelial secretion of von Willebrand factor by linking contractile actomyosin machinery to the plasma membrane
Authors: El-Mansi Sammy , Mitchell Tom P. , Miklavc Pika , Frick Manfred , Nightingale Thomas D. 
Published: August 2023

ABSTRACTBlood endothelial cells control the hemostatic and inflammatory response by secreting von Willebrand factor (VWF) and P-selectin from storage organelles called Weibel-Palade bodies (WPB). Actin-associated motor proteins regulate this secretory pathway at multiple points. Prior to fusion, myosin Va forms a complex that anchors WPBs to peripheral actin structures allowing maturation of content. Post-fusion, an actomyosin ring/coat is recruited and compresses to forcibly expel the largest VWF multimers. Here we provide the first evidence for the involvement of class I myosins during regulated VWF secretion. We show that unconventional myosin-1C (Myo1c) is recruited post fusion via its pleckstrin homology domain in an actin-independent process providing a link between the actin ring and phosphatidylinositol 4,5-bisphosphate (PIP2) at the membrane of the fused organelle. This is necessary to ensure maximal VWF secretion in response to secretagogue stimulation. Inhibition of class I myosins using the inhibitor Pentachloropseudilin alters the kinetics of the exocytic actin ring. These data offer new insight into the control of an essential physiological process and provide a new potential way in which it might be therapeutically controlled.SIGNFICANCE STATEMENTMyosin motors play diverse roles in regulated secretion. In endothelial cells, the role of conventional myosins (e.g. non-muscle myosin II) are well described however little is known about the requirement of unconventional myosins. Our data identify an important function of the class 1 myosin, Myosin-1C, in the actomyosin mediated expulsion of an essential blood clotting factor (von Willebrand factor) from endothelial cells. This is the first description of how class 1 myosins contribute to primary hemostasis and is therefore greatly improves our understanding of a fundamental physiological process.
Fundamental steps in Minichromosome Maintenance complex assembly are conserved from archaea to eukaryotes
Authors: Noble Oliver W , Degut Clement , Hodgkinson Michael R , Chong James P J , Plevin Michael J 
Published: August 2023

AbstractMinichromosome maintenance (MCM) proteins are the replicative helicase in both archaea and eukaryotes. Recent cryo-EM studies have defined key steps in the assembly pathway of the eukaryotic MCM2-7 complex and determined roles for each subunit. While archaeal MCMs are simpler in composition, we know little about how these homohexameric MCMs assemble. Investigation of archaeal MCMs has largely focussed on proteins from thermophilic organisms, which typically form robust oligomers under ambient experimental conditions, preventing dissection of their assembly pathway. Here, we describe an uncharacterised MCM from the mesophilic archaeonMancarchaeum acidophilum(MacMCM). A 3D structure ofMacMCM reveals subunit-subunit interfaces that are more similar to yeast MCM2-7 than previously studied MCMs from thermophilic archaea. We show that assembly of aMacMCM homohexamer on DNA proceeds via comparable steps to MCM2-7. These results reveal an ancient mechanism underlies assembly of the MCM complex, which is conserved from archaea to eukaryotes.
Aurora A mediated new phosphorylation of RAD51 is observed in Nuclear Speckles
Authors: Alaouid Mohamad , Ymbe Parfait Kenfack , Philippot-Ménil Vanessa , Cueff Gwennina , Demeyer Alexandre , Marquis Damien , Ayadi Nizar , Fleury Fabrice , Benhelli-Mokrani Houda 
Published: August 2023

ABSTRACTTo maintain its genome integrity, the cell uses complementary and orchestrated processes, among which is the DNA Damage Response. Pre mRNA maturation is an essential step of the DNA damage response that provides an adapted proteome in order to face genotoxic stress. We describe here a new phosphorylation of the RAD51 recombinase, on its Ser97 residue. This new Aurora A mediated RAD51 phosphorylation modulates itsin vitroactivity evaluated by D-loop and polymerization assays. Using recombinant proteins, we show that RAD51 is an RNA binding protein and that the Ser97 phosphorylation modulates its RNA binding affinityin vitro. Using a specifically generated antibody we revealed that this Ser97 phosphorylation is correlated with RAD51 localization into the RNA maturation membrane less organelles, Nuclear Speckles. We describe here for the first time the presence of RAD51 DNA repair factor within the Nuclear Speckles, raising the hypothesis of a possible role for RAD51 in splicing modulation. This point is of particular interest in the context of splicing profiles modulations associated with radio and/or chemoresistance.
Atlas ofDES(desmin) variants: Impact of variants located within the head domain on filament assembly
Authors: Voß Sabrina , Walhorn Volker , Holler Stephanie , Gärtner Anna , Pohl Greta , Gummert Jan , Anselmetti Dario , Milting Hendrik , Brodehl Andreas 
Published: August 2023

AbstractDesmin is a muscle-specific intermediate filament protein, which plays a significant role in providing structural integrity of cardiomyocytes by connecting different cell organelles and multi-protein complexes.DESmutations cause cardiomyopathies and skeletal myopathies. Most of these pathogenic mutations are localized in the highly conserved rod domain and affect the filament assembly.However, the impact ofDESvariants within the N-terminal head domain on the filament assembly process is widely unknown. Therefore, we inserted a set of 85 different head domain variants with unknown significance from human genetic databases in expression constructs and investigated their impact on filament formation in cell culture in combination with confocal microscopy. The majority of these desmin variants do not affect the filament assembly. However, the desmin variants -p.S13P, -p.N107D, -p.E108G and -p.K109E significantly inhibit the filament assembly. Additionally, we expressed and purified recombinant desmin and investigated the filament assembly defects by atomic force microscopy verifying these findings at the single molecular level. Furthermore, we truncated systematically the head domain to investigate which general parts of this domain are necessary for filament assembly.In summary, our functional investigations might be relevant for the classification of novelDESvariants and the genetic counselling of patients carrying desmin head variants.
Zinc-Induced Fluorescence Turn-on in Native and Mutant Phycoerythrobilin-Binding Orange Fluorescent Proteins
Authors: Jensen Gary C. , Janis Makena K. , Jara Jazzmin , Abbasi Nasir , Zastrow Melissa L. 
Published: August 2023

AbstractCyanobacteriochrome (CBCR)-derived fluorescent proteins are a class of reporters that can bind bilin cofactors and fluoresce across the ultraviolet to near-infrared spectrum. Derived from phytochrome-related photoreceptor proteins in cyanobacteria, many of these proteins use a single small GAF domain to autocatalytically bind a bilin and fluoresce. The second GAF domain of All1280 fromNostocsp. PCC7120 is a DXCF motif-containing protein that exhibits blue light-responsive photochemistry when bound to its native cofactor, phycocyanobilin. GAF2 can also bind non-photoswitching phycoerythrobilin (PEB), resulting in a highly fluorescent protein. Given the small size, high quantum yield, and that, unlike green fluorescent proteins, bilin-binding proteins can be used in anaerobic organisms, the orange fluorescent GAF2-PEB protein is a promising platform for designing new genetically encoded metal ion sensors. Here we show that GAF2-PEB undergoes a ∼5-fold reversible zinc-induced fluorescence enhancement with blue-shifted emission maximum (572 to 517 nm), which is not observed for a related PEB-bound GAF fromSynechocystissp. PCC6803 (Slr1393g3). Zn2+significantly enhances GAF2-PEB fluorescence across a biologically relevant pH range from 6.0–9.0 and with pH-dependent µM to nM dissociation constants. Site-directed mutants aiming to sterically decrease and increase access to PEB show a decreased and similar amount of zinc-induced fluorescence enhancement, respectively. Mutation of the cysteine residue within the DXCF motif to alanine abolishes zinc-induced fluorescence enhancement. Collectively, these results support the presence of a fluorescence enhancing Zn2+binding site in GAF2-PEB likely involving coordination to the bilin cofactor and requiring a nearby cysteine residue.
The cerebellum acts as the analog to the medial temporal lobe for sensorimotor memory
Authors: Hadjiosif Alkis M. , Gibo Tricia L. , Smith Maurice A. 
Published: August 2023

AbstractThe cerebellum is critical for sensorimotor learning. The specific contribution that it makes, however, remains unclear. Inspired by the classic finding that, for declarative memories, medial temporal lobe structures provide a gateway to the formation of long-term memory but are not required for short-term memory, we hypothesized that, for sensorimotor memories, the cerebellum may play an analogous role. Here we studied the sensorimotor learning of individuals with severe ataxia from cerebellar degeneration. We dissected the memories they formed during sensorimotor learning into a short-term temporally-volatile component, that decays rapidly with a time constant of just 15-20sec and thus cannot lead to long-term retention, and a longer-term temporally-persistent component that is stable for 60 sec or more and leads to long-term retention. Remarkably, we find that these individuals display dramatically reduced levels of temporally-persistent sensorimotor memory, despite spared and even elevated levels of temporally-volatile sensorimotor memory. In particular, we find both impairment that systematically increases with memory window duration over shorter memory windows (<12 sec) and near-complete impairment of memory maintenance over longer memory windows (>25 sec). This dissociation uncovers a new role for the cerebellum as a gateway for the formation of long-term but not short-term sensorimotor memories, mirroring the role of the medial temporal lobe for declarative memories. It thus reveals the existence of distinct neural substrates for short-term and long-term sensorimotor memory, and it explains both newly-identified trial-to-trial differences and long-standing study-to-study differences in the effects of cerebellar damage on sensorimotor learning ability.Significance StatementA key discovery about the neural underpinnings of memory, made more than half a century ago, is that long-term, but not short-term, memory formation depends on neural structures in the brain’s medial temporal lobe (MTL). However, this dichotomy holds only for declarative memories – memories for explicit facts such as names and dates – as long-term procedural memories – memories for implicit knowledge such as sensorimotor skills – are largely unaffected even with substantial MTL damage. Here we demonstrate that the formation of long-term, but not short-term, sensorimotor memory depends on a neural structure known as the cerebellum, and we show that this finding explains the variability previously reported in the extent to which cerebellar damage affects sensorimotor learning.
Cyclin B3 is a dominant fast-acting cyclin that drives rapid early embryonic mitoses
Authors: Lara-Gonzalez Pablo , Variyar Smriti , Budrewicz Jacqueline , Schlientz Aleesa , Varshney Neha , Bellaart Andrew , Moghareh Shabnam , Nguyen Anh Cao Ngoc , Oegema Karen , Desai Arshad 
Published: August 2023

ABSTRACTIn many species, early embryonic mitoses proceed at a very rapid pace, but how this pace is achieved is not understood. Here we show that in the earlyC. elegansembryo, cyclin B3 is the dominant driver of rapid embryonic mitoses. Metazoans typically have three cyclin B isoforms that associate with and activate Cdk1 kinase to orchestrate mitotic events: the related cyclins B1 and B2 and the more divergent cyclin B3. We show that whereas embryos expressing cyclins B1 and B2 support slow mitosis (NEBD to Anaphase ∼ 600s), the presence of cyclin B3 dominantly drives the ∼3-fold faster mitosis observed in wildtype embryos. CYB-1/2-driven mitosis is longer than CYB-3-driven mitosis primarily because the progression of mitotic events itself is slower, rather than delayed anaphase onset due to activation of the spindle checkpoint or inhibitory phosphorylation of the anaphase activator CDC-20. Addition of cyclin B1 to cyclin B3-only mitosis introduces an ∼60s delay between the completion of chromosome alignment and anaphase onset, which likely ensures segregation fidelity; this delay is mediated by inhibitory phosphorylation on CDC-20. Thus, the dominance of cyclin B3 in driving mitotic events, coupled to introduction of a short cyclin B1-dependent delay in anaphase onset, sets the rapid pace and ensures fidelity of mitoses in the earlyC. elegansembryo.
The mTOR pathway genesmTOR,Rheb,Depdc5,Pten, andTsc1have convergent and divergent impacts on cortical neuron development and function
Authors: Nguyen Lena H. , Xu Youfen , Nair Maanasi , Bordey Angelique 
Published: August 2023

ABSTRACTBrain somatic mutations in various components of the mTOR complex 1 (mTORC1) pathway have emerged as major causes of focal malformations of cortical development and intractable epilepsy. While these distinct gene mutations converge on excessive mTORC1 signaling and lead to common clinical manifestations, it remains unclear whether they cause similar cellular and synaptic disruptions underlying cortical network hyperexcitability. Here, we show thatin uteroactivation of the mTORC1 activators,RhebormTOR, or biallelic inactivation of the mTORC1 repressors,Depdc5,Tsc1, orPtenin mouse medial prefrontal cortex leads to shared alterations in pyramidal neuron morphology, positioning, and membrane excitability but different changes in excitatory synaptic transmission. Our findings suggest that, despite converging on mTORC1 signaling, mutations in different mTORC1 pathway genes differentially impact cortical excitatory synaptic activity, which may confer gene-specific mechanisms of hyperexcitability and responses to therapeutic intervention.
The evaluation on the protection performance of high temperature sacrificial anode for ABS A steels in H2S-containing environment
Authors: Zhao Yongtao , Li Weili , Xuan Xiaoyang , Gao Jianbang , Wang Jue , Dong Liang , Zang Dawei , Wang Mingjian , Zhong Xiankang 
Published: August 2023

Purpose
This study aims to evaluate the protection performance of zinc as sacrificial anode for ABS A steel in the presence of H2S under different temperatures, pH and salinities.

Design/methodology/approach
In this paper, weight loss measurements and electrochemical measurements are used to evaluate the corrosion degree of zinc and ABS A steel.

Findings
Under the conditions involved in this work, it is shown that zinc is a nice sacrificial anode with the reason of its stable potential and excellent anode current efficiency according to the relevant standard. And it is also found that the hydrogen evolution does not occur on ABS A steel specimens. The potential difference between cathode and anode is suitable; thus, it can be concluded that each steel is well protected.

Originality/value
To the best of the authors’ knowledge, no other study has analyzed the protection mechanism and effect of zinc as sacrificial anode in H2S-containing environments under high temperature at present.
Keeping the ball rolling: using the S-O-R framework to investigate the determinants of football fan loyalty
Authors: Rahman Mohammad M. , Rosenberger Philip J. , Yun Jin Ho , de Oliveira Mauro José , Köcher Sören 
Published: August 2023

PurposeInsights into how fan experience can be used to cultivate football (soccer) fan loyalty are limited. Based on the stimulus–organism–response (S-O-R) paradigm, this study develops and tests a theoretical model investigating the effects of football-game socialisation, team interest, football interest and transaction satisfaction (stimuli) on fanship and cumulative satisfaction (organism), and subsequently, attitudinal loyalty and behavioural loyalty (response). National culture was a moderator.Design/methodology/approachA self-administered online survey collected data from a convenience sample of 762 football fans from Brazil, China and Germany.FindingsThe PLS-SEM results support the S-O-R based model, indicating that football fan-loyalty behaviours are determined by fanship and cumulative satisfaction with the team. Fan experiences, in turn, are also found to be influenced by fan perceptions relating to socialisation, team interest, football interest and transaction satisfaction—elements over which the football team's management may exert some degree of control. Some national cultural differences were found, with three of the model's 12 structural paths significantly different for Germany vis-à-vis Brazil.Originality/valueThis study advances the authors’ understanding of the significance of socialisation and fan-interest factors for football, providing evidence supporting the role of the fan experience and service-consumption stimuli related to those game experiences as significant drivers (stimuli) of the fan's affective (fanship) and cognitive states (cumulative satisfaction). This study enriches the limited body of evidence on fanship's role as a driver of attitudinal and behavioural loyalty. Finally, the multi-country study partially supports the moderation effect of national culture.
Risk-taking by banks: evidence from European Union countries
Authors: Garcia Maria Teresa Medeiros , Ye Ana Jin 
Published: August 2023

PurposeThe aim of this paper is to study the relationship between banks' ownership structure and their risk-taking behavior as well as the impact of banking regulation on banks' approach to taking risk, after the 2008 financial crisis.Design/methodology/approachThe empirical analysis considers a sample of listed banks from European Union (EU) countries, over the period of 2011–2016 and uses the generalized least squared (GLS) random effect (RE) method, following Baltagi and Wu (1999) and Pathan (2009).FindingsThe authors find that the structure of the board of directors can influence bank risk behavior but not the ownership concentration. No significant relation was found between the influence of the regulatory environment and bank risk, i.e., stricter regulation has no effect on risk taking by banks.Originality/valueThe paper contributes to the literature in risk measures and banks' corporate governance. It also considers the impact of regulatory framework on banks' risk-taking behavior. The aim of this empirical analysis was to examine in greater detail these subjects and the dynamics between them after the significant structural changes in the macroeconomic environment and in the financial system, particularly with regards the regulatory and supervisory framework following the 2008 financial crisis, using data from European Union countries.
Advanced intelligent health advice with informative summaries to facilitate treatment decision-making
Authors: Liu Yi-Hung , Chen Sheng-Fong 
Published: August 2023

Purpose
Whether automatically generated summaries of health social media can assist users in appropriately managing their diseases and ensuring better communication with health professionals becomes an important issue. This paper aims to develop a novel deep learning-based summarization approach for obtaining the most informative summaries from online patient reviews accurately and effectively.

Design/methodology/approach
This paper proposes a framework to generate summaries that integrates a domain-specific pre-trained embedding model and a deep neural extractive summary approach by considering content features, text sentiment, review influence and readability features. Representative health-related summaries were identified, and user judgements were analysed.

Findings
Experimental results on the three real-world health forum data sets indicate that awarding sentences without incorporating all the adopted features leads to declining summarization performance. The proposed summarizer significantly outperformed the comparison baseline. User judgement through the questionnaire provides realistic and concrete evidence of crucial features that remarkably influence patient forum review summaries.

Originality/value
This study contributes to health analytics and management literature by exploring users’ expressions and opinions through the health deep learning summarization model. The research also developed an innovative mindset to design summarization weighting methods from user-created content on health topics.
Reducing forced labour in supply chains: what could traditional companies learn from social enterprises?
Authors: Vanpoucke Evelyne , Klassen Robert D. 
Published: August 2023

PurposeForced labour is one of the most exploitative practices in supply chains, generating serious human right abuses. The authors seek to understand how relationships for reducing forced labour are influenced by institutional logics. The emerging supply chain efforts of social enterprises offer particularly intriguing approaches, as their social mission can spur creative new approaches and reshape widely adopted management practices.Design/methodology/approachThe authors study supplier relationships in the smartphone industry and compare the evolving practices of two cases: the first, a growing novel social enterprise; and the second, a high-profile commercial firm that has adopted a progressive role in combating forced labour.FindingsThe underlying institutional logic influenced each firm's willingness to act beyond its direct suppliers and to collaborate in flexible ways that create systematic change. Moreover, while both focal firms had clear, well-documented procedures related to forced labour, the integration, rather than decoupling, of forced labour and general supply chain policies provided a more effective way to reduce the risks of forced labour in social enterprises.Research limitations/implicationsAs authors’ comparative case study approach may lack generalizability, future research is needed to broadly test their propositions.Practical implicationsThe paper identifies preconditions in terms of institutional logics to successfully reduce the risk of forced labour in supply chains.Originality/valueThis paper discusses how social enterprises can provide a learning laboratory that enables commercial firms to identify options for supplier relationship improvement.