bluuebunny/crossref_metadata_2025_split huggingface dataset:
LDO proteins and Vac8 form a vacuole-lipid droplet contact site required for lipophagy in response to starvation
Authors: Álvarez-Guerra Irene , Block Emma , Broeskamp Filomena , Gabrijelčič Sonja , de Ory Ana , Habernig Lukas , Andréasson Claes , Levine Tim P. , Höög Johanna L. , Büttner Sabrina 
Published: April 2023

SummaryLipid droplets (LDs) are fat storage organelles critical for energy and lipid metabolism. Upon nutrient exhaustion, cells consume LDs via gradual lipolysis or via lipophagy, theen blocuptake of LDs into the vacuole. Here, we show that LDs dock to the vacuolar membrane via a contact site that is required for lipophagy in yeast. The LD-localized LDO proteins carry an intrinsically disordered region that associates with vacuolar Vac8 to form vCLIP, the vacuolar-LD contact site. Nutrient limitation drives vCLIP formation, and its inactivation blocks lipophagy. Vac8 is sufficient to recruit LDs to cellular membranes. We establish a functional link between lipophagy and microautophagy of the nucleus, both requiring Vac8 to form respective contact sites upon metabolic stress. In sum, we unravel the molecular architecture of vCLIP, a contact site required for lipophagy, and find that Vac8 provides a platform for multiple and competing contact sites associated with autophagy.
Neuroticism and emotion regulation: An effective connectivity analysis of large-scale resting-state brain networks
Authors: Sultana Tajwar , Hasan Muhammad Abul , Razi Adeel 
Published: April 2023

AbstractThe neurotic personality has an impact on the regulation of basic negative emotions such as anger, fear, and sadness. There has been extensive research in search of functional connectivity biomarkers of neuroticism and basic negative emotions but there is a lack of research based on effective connectivity. In the current research, we intended to determine the significance of causal interaction of three large-scale resting-state networks – default mode, salience, and executive networks – to predict neuroticism and basic negative emotions. In this study, a large-scale human connectome project dataset comprising functional MRI scans and self-reported scores of neuroticism and negative emotions of 1079 subjects, was utilized. Spectral dynamic causal modelling and parametric empirical Bayes was used to estimate the subject-level effective connectivity parameters and their group-level associations with the neuroticism and emotional scores. Leave-one-out cross-validation using parametric empirical Bayes was employed for prediction analysis. Our results for heightened emotions showed that the self-connection of right hippocampus can predict individuals with high fear, self-connections of dorsal anterior cingulate cortex, posterior cingulate cortex and left dorsolateral prefrontal cortex can predict individuals with high sadness. High anger, low sadness, and neuroticism scores of any emotion category except low fear, could not be predicted using triple network effective connectivity. Our findings revealed that the causal (directed) connections of the resting-state triple network can potentially serve as a connectomic signature for people with high and low fear, high sadness, low anger, and neuroticism with low fear.
DNA damage-induced interaction between a lineage addiction oncogenic transcription factor and the MRN complex shapes a tissue-specific DNA Damage Response and cancer predisposition
Authors: Binet Romuald , Lambert Jean-Philippe , Tomkova Marketa , Tischfield Samuel , Baggiolini Arianna , Picaud Sarah , Sarkar Sovan , Louphrasitthiphol Pakavarin , Dias Diogo , Carreira Suzanne , Humphrey Timothy , Fillipakopoulos Panagis , White Richard , Goding Colin R 
Published: April 2023

AbstractSince genome instability can drive cancer initiation and progression, cells have evolved highly effective and ubiquitous DNA Damage Response (DDR) programs. However, some cells, in skin for example, are normally exposed to high levels of DNA damaging agents. Whether such high-risk cells possess lineage-specific mechanisms that tailor DNA repair to the tissue remains largely unknown. Here we show, using melanoma as a model, that the microphthalmia-associated transcription factor MITF, a lineage addition oncogene that coordinates many aspects of melanocyte and melanoma biology, plays a non-transcriptional role in shaping the DDR. On exposure to DNA damaging agents, MITF is phosphorylated by ATM/DNA-PKcs, and unexpectedly its interactome is dramatically remodelled; most transcription (co)factors dissociate, and instead MITF interacts with the MRE11-RAD50-NBS1 (MRN) complex. Consequently, cells with high MITF levels accumulate stalled replication forks, and display defects in homologous recombination-mediated repair associated with impaired MRN recruitment to DNA damage. In agreement, high MITF levels are associated with increased SNV burden in melanoma. Significantly, the SUMOylation-defective MITF-E318K melanoma predisposition mutation recapitulates the effects of ATM/DNA-PKcs-phosphorylated MITF. Our data suggest that a non-transcriptional function of a lineage-restricted transcription factor contributes to a tissue-specialised modulation of the DDR that can impact cancer initiation.
Renal Cl-/H+ antiporter ClC-5 regulates collagen production and release in Dent Disease models
Authors: Duran M. , Ariceta G. , Semidey ME , Castells-Esteve C , Lu B. , Meseguer A. , Cantero-Recasens G. 
Published: April 2023

ABSTRACTMutations in the Cl-/H+antiporter ClC-5 cause Dent’s Disease 1 (DD1), a rare primary tubulopathy that eventually progresses to renal failure. In fact, even with normal kidney function, DD1 patients present renal tubulointerstitial fibrosis. However, the link between ClC-5 loss-of-function and renal fibrosis remains unclear. Here, we have shown that DD1 mice models lacking ClC-5 present higher renal collagen deposition and fibrosis. Accordingly, deletion of ClC-5 in human renal proximal tubule epithelial cells (CLCN5KD) recapitulates this effect. We have demonstrated thatCLCN5KD causes an increase of collagen I (Col I) and IV (Col IV) intracellular levels by promoting their transcription through β-catenin pathway and impairing their lysosomal-mediated degradation. In addition,CLCN5KD cells release more Col I and IV at the extracellular space that form fibres with altered properties and resistance to removal compared to control cells. Altogether, we describe a new regulatory mechanism for collagens’ production and release by ClC-5, which is altered in DD1 and provides a better understanding of disease progression to renal fibrosis.SIGNIFICANCE STATEMENTRenal fibrosis is a common pathologic process occurring as consequence of chronic kidney injury and leading to renal dysfunction. Dent’s Disease is a rare renal pathology that progresses to chronic kidney disease and tubulointerstitial fibrosis. Interestingly, it is caused by mutations in a single gene calledCLCN5, therefore it can help understanding the cellular mechanisms of renal fibrosis. Using cellular and mice models of the disease, we describe a mechanism linkingCLCN5function, cell differentiation and regulation of collagen levels, major component of extracellular matrix and important player for renal fibrosis development. In conclusion, our results provide a link betweenCLCN5and altered collagen deposition, which could be relevant for other renal Fanconi syndrome related diseases also progressing to fibrosis.
Spatial transcriptome profiling uncovers metabolic regulation of left-right patterning
Authors: Yagi Hisato , Cui Cheng , Saydmohammed Manush , Gabriel George , Baker Candice , Devine William , Wu Yijen , Lin Jiuann-huey , Malek Marcus , Bais Abha , Murray Stephen , Aronow Bruce , Tsang Michael , Kostka Dennis , Lo Cecilia W. 
Published: April 2023

AbstractLeft-right patterning disturbance can cause severe birth defects, but it remains least understood of the three body axes. We uncovered an unexpected role for metabolic regulation in left-right patterning. Analysis of the first spatial transcriptome profile of left-right patterning revealed global activation of glycolysis, accompanied by right-sided expression ofBmp7and genes regulating insulin growth factor signaling. Cardiomyocyte differentiation was left-biased, which may underlie the specification of heart looping orientation. This is consistent with knownBmp7stimulation of glycolysis and glycolysis suppression of cardiomyocyte differentiation. Liver/lung laterality may be specified via similar metabolic regulation of endoderm differentiation.Myo1d, found to be left-sided, was shown to regulate gut looping in mice, zebrafish, and human. Together these findings indicate metabolic regulation of left-right patterning. This could underlie high incidence of heterotaxy-related birth defects in maternal diabetes, and the association of PFKP, allosteric enzyme regulating glycolysis, with heterotaxy. This transcriptome dataset will be invaluable for interrogating birth defects involving laterality disturbance.
Mitochondrial genome editing: a possible interplay of atherosclerosis-associated mutation m.15059G>A with defective mitophagy
Authors: Khotina Victoria A. , Kalmykov Vladislav A. , Zhuravlev Alexander D. , Sinyov Vasily V. , Sobenin Igor A. , Orekhov Alexander N. , Sukhorukov Vasily N. 
Published: April 2023

ABSTRACTBackgroundIt was assumed that the cause of chronic inflammation in atherosclerosis is a disturbance of the innate immunity response, caused, among other factors, by mitochondrial dysfunctions. It was also suggested that mitochondrial dysfunction may be caused by heteroplasmic mutations in mitochondrial DNA. The aim of this study was to evaluate the effect of the mitochondrial nonsense mutation m.15059G>A on cellular functions in atherosclerosis: lipoidosis, pro-inflammatory response, and mitophagy.MethodsThe human monocytic cell line THP-1 and cytoplasmic hybrid cell line TC-HSMAM1 were used. An original approach based on the CRISPR/Cas9 system was developed and used for the elimination of mtDNA copies carrying the m.15059G>A mutation in theMT-CYBgene. Using this approach, the Cas9-TC-HSMAM1 cells with an eliminated m.15059G>A mutation was obtained. The gene expression levels of genes encoding enzymes related to cholesterol metabolism were analyzed by quantitative RT-PCR. The evaluation of pro-inflammatory cytokine secretion was assessed using ELISA. Mitophagy in cells was detected using confocal microscopy.ResultsIn contrast to intact TC-HSMAM1 cybrids, in Cas9-TC-HSMAM1 cells, incubation with atherogenic LDL led to a decrease in the expression of the gene encoding fatty acid synthase (FASN). It was found that TC-HSMAM1 cybrids are characterized by defective mitophagy and are also unable to reduce the production of pro-inflammatory cytokines (to form immune tolerance) in response to repeated LPS stimulation. Elimination of mtDNA carrying the m.15059G>A mutation led to the restoration of immune tolerance and activation of mitophagy in the studied cells.ConclusionsThe m.15059G>A mutation was found to be associated with defective mitophagy, immune tolerance, and impaired metabolism of intracellular lipids due to upregulation of theFASN. Thus, this mutation may play an important role in atherogenesis due to its contribution to the chronification of inflammation, which aggravates the progression of atherosclerosis.
CHAF1A promotes the translesion DNA synthesis pathway in response to DNA replication stress
Authors: Wen Bing , Zheng Hai-Xiang , Deng Dan-Xia , Zhang Zhi-Da , Heng Jing-Hua , Liao Lian-Di , Xu Li-Yan , Li En-Min 
Published: April 2023

AbstractThe translesion DNA synthesis (TLS) pathway mediated by proliferating cell nuclear antigen (PCNA) monoubiquitination is an essential mechanism by which cancer cells bypass DNA damage caused by DNA replication stress to maintain genomic stability and cell survival. Chromatin assembly factor 1 subunit A (CHAF1A) traditionally promotes histone assembly during DNA replication. Here, we revealed that CHAF1A is a novel regulator of the TLS pathway. High expression of CHAF1A is significantly associated with poor prognosis in cancer patients. CHAF1A promotes fork restart under DNA replication stress and maintains genome integrity. CHAF1A enhances the interaction between PCNA and E3 ubiquitin protein ligase RAD18 and promotes PCNA monoubiquitination, thereby promoting the recruitment of Y-family DNA polymerase Pol η and enhancing cancer cell resistance to stimuli that trigger replication fork blockade. Mechanistically, CHAF1A-mediated PCNA monoubiquitination is independent of CHAF1A-PCNA interaction. CHAF1A interacts with both RAD18 and replication protein A2 (RPA2), mediating RAD18 binding on chromatin in response to DNA replication stress. Taken together, these findings improve our understanding of the mechanisms that regulate the TLS pathway and provide insights into the relationship between CHAF1A and the malignant progression of cancers.
Investigation of microstructure of fretting wear behavior in 6061-T6 aluminum alloy
Authors: Erturun Veysel , Odabaş Durmuş 
Published: April 2023

Purpose
The purpose of this study is to investigate the microstructure of fretting wear behavior in 6061-T6 aluminum alloy. The fretting wear of blind riveted lap joints of 6061-T6 aluminum alloy plates, which are widely used in aircraft construction, was investigated. Fretting damages were investigated between the contact surface of the plates and between the plate and the rivet contact surface.

Design/methodology/approach
Experiments were carried out using a computer controlled Instron testing machine with 200 kN static and 100 kN dynamic load capacity. Max package computer program was used for the control of the experiments. Fretting scars, width of wear scars, microstructure was investigated by metallographic techniques and scanning electron microscopy.

Findings
It was found that fretting damages were occurred between the plates contacting surface and between the plate and rivet contact surface. As load and cycles increased, fretting scars increased. Fretting wear initially begins with metal-to-metal contact. Then, the formed metallic wear particles are hardened by oxidation. These hard particles spread between surfaces, causing three-body fretting wear. Fretting wear surface width increases with increasing load and number of cycles.

Originality/value
The useful life of many tribological joints is limited by wear or deterioration of the fretting components due to fretting by oscillating relative displacements of the friction surfaces. Such displacements are caused by vibrations, reciprocating motion, periodic bending or twisting of the mating component, etc. Fretting also tangibly reduces the surface layer quality and produces increased surface roughness, micropits, subsurface microphone.
Field BIM and mobile BIM technologies: a requirements taxonomy and its interactions with construction management functions
Authors: Jowett Benjamin , Edwards David John , Kassem Mohamad 
Published: April 2023

Purpose
This study aims to develop a taxonomy of requirements for mobile BIM technologies (MBT), clarify the relating terms and concepts, and identify the interactions between MBT features and the construction management functions on sites.

Design/methodology/approach
A positivist approach with elements of interpretivism is adopted to allow to capture what is perceived as “reality” in relation to individuals’ interpretation and experience in the use and implementation of MBT. This is achieved by using a mixed qualitative-quantitative approach that can capture the various understandings of MBT. The research methods included a longitudinal case study over 12 months, two project workshops, expert interviews and an industry survey that together helped to investigate MBT at project, enterprise and industry levels.

Findings
The MBT requirements taxonomy included requirements relating to both project and organisation. Project requirements addressed MBT functionalities for sites and information management, while organisation requirements focused on the integration of MBT solutions with the enterprise from information technology, legal and security perspectives. A detailed matrix showing the interactions between five key MBT features and seven construction management functions was also developed.

Research limitations/implications
The two constructs developed by this study can help researchers to structure their investigation of key uses of MBT applications and their benefits. It can be used by researchers aiming to investigate integrated approaches to the digitalisation of construction sites, such as those enabled by Digital Twins. The interaction matrix can aid researchers in evaluating the intersections between the MBT functionalities and the site construction management functions (e.g. theoretical analysis of interactions from Lean Construction, benefit evaluation perspective). More broadly, the two constructs can support research and practice investigating the development of data-driven approaches on construction sites.

Practical implications
The developed MBT taxonomy can guide construction organisations in selecting suitable MBT for Field BIM for their projects. It can also act as a baseline against which varying MBT solutions can be compared.

Originality/value
Constructs such as taxonomies for MBTs; an understanding of MBT capabilities and use within the industry; and a lack of delineation between related terms, such as Mobile BIM, Field BIM, Site BIM, Cloud BIM and Mobile Apps, were lacking in the literature. This study contributed to addressing this gap.
Reduction of exceeding the guaranteed service time for external trucks at the DCT Gdańsk container terminal using a six sigma framework
Authors: Moszyk Karol , Deja Mariusz 
Published: April 2023

Purpose
The purpose of this paper is to investigate ways to reduce the average amount of exceeded guaranteed service time for external trucks at Deepwater Container Terminal Gdańsk Sp z o.o. (DCT Gdańsk) via dosing the gate activities, in particular IN-Gate entry process, of trucks carrying import/export/transit containers.

Design/methodology/approach
A Six Sigma methodology with the define, measure, analyze, improve, and Control (DMAIC) methods along with the SIPOC chart, cause and effect diagram, scatterplot, benchmark and brainstorming and finally multi-voting tool are used as analyses tools in this research.

Findings
DCT Gdańsk reorganized and modernized the gate operations. Gate reorganization and modernization include streaming line traffic at the gates, external parking lot optimization, implementation of dedicated supporting software and installation of dedicated CCTV cameras to provide 24 h live view. During gates development, the external truck service times data were collected and analysed. The obtained materials concerned the measurement of the average truck turnaround time before and after the implementation of the improvements.

Originality/value
The proposed approach of reducing the average amount of exceeded guaranteed service time of external trucks at the container terminal is unique and relatively cheap mainly due to organizational changes with some widely available low-cost investments and can be applied on a different scale to other container terminals or to transport and logistics companies.
The role of signals in new venture financing in the context of an emerging market: a configurational approach
Authors: Topaler Başak , Adar Gülcan 
Published: April 2023

PurposeThis study proposes a portfolio of new venture signals that are likely to attract investors' attention in the context of an emerging market and examines how they work in combination to affect the likelihood of obtaining funding.Design/methodology/approachThe authors use data on early-stage venture capital investments for high-tech start-ups in Turkey. The authors adopt a configurational approach and use fuzzy QCA and regression analysis.FindingsThe findings suggest that financing of new ventures in an emerging economy is shaped by signals of context-specific capabilities that are required to survive and thrive in this market environment alongside and in interaction with signals of general capabilities required for business success. Different combinations of these signals provide equifinal pathways to obtain funding. Furthermore, signals that differ in type and content interact in complex ways to affect investors' decisions.Practical implicationsThe findings suggest that entrepreneurs with no prior experience in the emerging market context can increase their chances of obtaining funding by affiliating with a venture development organization. Another promising strategy is to form a founding team that includes members affiliated with a developed country together with members who have emerging market experience. Finally, entrepreneurs may consider combining signals of context-specific capabilities with signals of general capabilities as they work in a complementary way to attract funding.Originality/valueThis study addresses two major shortcomings of the literature on new venture signaling, first, by positing the emerging market context as a unique signaling environment and, second, by demonstrating the value of considering signals as portfolios with potential interdependencies.
Exploring the barriers and motivators of value co-creation through a theoretical lens of service-dominant logic
Authors: Ajmal Mian M. , Jan Amin , Khan Mehmood , Hussain Matloub , Salameh Anas A. 
Published: April 2023

Purpose
This study aims to identify and categorize the barriers and motivators to value co-creation and to establish its theoretical link with the five axioms of value co-creation.

Design/methodology/approach
The study used a qualitative approach based on a bibliographic literature review for identifying barriers and motivators of value co-creation. Subsequently, this study grouped those barriers and motivators into three categories. It further linked those barriers and motivators with five axioms of value co-creation using the grounded theory.

Findings
Results based on the categorization of barriers show that the first category “organization and system-related barriers” is associated with Axioms 1, 2 and 5 of the service-dominant logic. The second category “customer-oriented barriers” is associated with Axioms 2, 4 and 5. The third category of barriers “social environmental and economic barriers” is related to only Axiom 3. Results based on the motivators show that the first category “organization and system-related motivators” is associated with Axioms 2 and 4. The second category of “customer-oriented motivators” is associated with Axioms 1, 2, 3 and 5. The third category of motivators “social environmental and economic motivators” is related to Axioms 3 and 5.

Practical implications
These results provide insights to managers for eradicating barriers from the value co-creation process by emphasizing strategic intrusion into those axioms that contain a high percentage of barriers. Similarly, it also provides insights to managers for expediting motivators of value co-creation by strategic intrusion based on the axioms that contain a high percentage of motivators. Overall, this study will serve for greater value co-creation by eradicating barriers and promoting motivators. This study also provides a theoretical foundation for future studies intended to establish a theoretical connection between the barriers and motivators with value co-creation in other industries.

Originality/value
This study is novel in terms of identifying barriers and motivators of value creation by categorizing those identified barriers and motivators into three sub-categories. This study is the first one for linking barriers and motivators with five axioms of value creation for a micro-level policy formulation.