bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Lef1 activation accelerates iPSC-derived keratinocytes differentiation in Hutchinson-Gilford Progeria Syndrome
Authors: Mao Xiaojing , Xiong Zheng-Mei , Xue Huijing , Brown Markus A. , Gete Yantenew G. , Yu Reynold , Sun Linlin , Cao Kan 
Published: February 2022

AbstractHutchinson-Gilford progeria syndrome (HGPS) is a detrimental premature aging disease caused by a point mutation in the human LMNA gene. This mutation results in the abnormal accumulation of a truncated pre-lamin A protein called progerin. Among the drastically accelerated signs of aging in HGPS patients, severe skin phenotypes such as alopecia and sclerotic skins always develop with the disease progression. Here, we study the HGPS molecular mechanisms focusing on early skin development by differentiating patient-derived induced pluripotent stem cells (iPSCs) to a keratinocyte lineage. Interestingly, HGPS iPSCs showed an accelerated commitment to the keratinocyte lineage than the normal control. To study potential signaling pathways that accelerated skin development in HGPS, we investigated the WNT pathway components during HGPS iPSCs-keratinocytes induction. Surprisingly, despite the unaffected β-catenin activity, the expression of a critical WNT transcription factor LEF1 was diminished from an early stage in HGPS iPSCs-keratinocytes differentiation. Chromatin immunoprecipitation (ChIP) experiment further revealed strong bindings of LEF1 to the early-stage epithelial developmental markers K8 and K18 and that the LEF1 silencing by siRNA down-regulates the K8/K18 transcription. During the iPSCs-keratinocytes differentiation, correction of HGPS mutation by Adenine base editing (ABE), while in a partial level, rescued the phenotypes for accelerated keratinocyte lineage-commitment. ABE also reduced the cell death in HGPS iPSCs-derived keratinocytes. These findings brought new insight into the molecular basis and therapeutic application for the skin abnormalities in HGPS.
Introducing an argonaute-facilitated PCR platform
Authors: Gao Feng , Han Bojia , Chen Yin , Sun Fangfang , Yang Jianhui , Han Chun-Yu 
Published: February 2022

AbstractArgonaute proteins are characterized by highly efficient guide DNA/RNA-directed binding to target nucleic acids with high fidelity. Employing this feature, we designed an argonaute-facilitated PCR platform by making use of an argonaute derived from Mesorhizobium japonicum (MejAgo) which does not carry nuclease activity and exposes the 3’ end of guide DNA when binding. Each reaction cycle of the MejAgo-PCR platform consists of a denaturing step and a polymerase-mediated extension step, omitting the annealing step required by the traditional PCR. More importantly, MejAgo-PCR could significantly improve the sensitivity of PCR in template detection due to the argonaute-facilitated pairing between guide DNA/primer and template. Thus, an argonaute-facilitated PCR has the potential to be developed as an advanced PCR platform with higher sensitivity and efficiency.
Structure-based design and characterization of Parkin activating mutations
Authors: Stevens Michael U. , Croteau Nathalie , Eldeeb Mohamed A. , Zeng Zhi Wei , Toth Rachel , Durcan Thomas M. , Springer Wolfdieter , Fon Edward A. , Muqit Miratul M. K. , Trempe Jean-François 
Published: February 2022

AbstractHuman autosomal recessive mutations in the Parkin gene are causal for Parkinson’s disease (PD). Parkin encodes a ubiquitin E3 ligase that functions together with the PD associated kinase, PINK1, in a mitochondrial quality control pathway. Structural studies reveal that Parkin exists in an inactive conformation mediated by multiple autoinhibitory domain interfaces. Here we have performed comprehensive mutational analysis of both human and rat Parkin to unbiasedly determine Parkin activating mutations across all major autoinhibitory interfaces. Out of 31 mutations tested, we identify 11 activating mutations clustered near the RING0:RING2 or REP:RING1 interfaces, which reduce the thermal stability of Parkin. Of these, we demonstrate that three mutations, V393D, A401D, and W403A located at the REP:RING1 interface were able to completely rescue a Parkin S65A mutant, defective in mitophagy, in cell-based studies. Overall our data extends previous analysis of Parkin activation mutants and suggests that small molecules that mimic REP:RING1 destabilisation offer therapeutic potential for PD patients harbouring select Parkin mutations.Summary blurbParkin, an E3 ubiquitin ligase involved in Parkinson’s disease, is inactive in the basal state and is activated by PINK1 to mediate mitophagy. Here we characterized 31 mutations and discovered three that activate Parkin and rescue loss of PINK1 phosphorylation.
Cell cycle progression requires repression by Groucho during S-phase and its relief at G2-phase
Authors: Bar-Cohen Shaked , Paroush Ze’ev 
Published: February 2022

AbstractThe cell cycle depends on a sequence of steps that are triggered and terminated via the synthesis and degradation of phase-specific transcripts and proteins. While much is known about how stage-specific transcription is activated, less is understood about how inappropriate gene expression is suppressed. In this paper we demonstrate that Groucho, the Drosophila orthologue of TLE1 and other related human transcriptional corepressors, regulates cell cycle progression in vivo. We show that although Groucho is expressed throughout the cell cycle, its activity is selectively inactivated by phosphorylation, except during S-phase when it represses e2f1 expression. Misregulated Groucho activity causes cell cycle arrest; in particular, both constitutive Groucho activity and failure to repress e2f1 cause cell cycle arrest phenotypes. We also show that the Cdk1 kinase is responsible for stage-specific phosphorylation of Groucho in vivo. We propose that Groucho and its orthologues play key roles in the metazoan cell cycle that may explain the links between TLE corepressors and several types of human cancer.
Long-term ketogenic diet increases expression of SOX2-dependent oligodendrocyte- and myelination-associated genes in the aged mouse brain
Authors: Stratton Matthew S. , Lopez-Dominguez Jose Alberto , Canella Alessandro , Ramsey Jon J. , Cortopassi Gino A. 
Published: February 2022

AbstractAging is associated with multiple neurodegenerative conditions that severely limit quality of life and shorten lifespan. Studies in rodents indicate that in addition to extending lifespan, the ketogenic diet improves cognitive function in aged animals, thus improving healthspan. To broadly investigate what mechanisms might be activated in the brain in response to ketogenic diet, we conducted transcriptome wide analysis on whole brain samples from 13-month-old mice, 26-month-old mice, and 26-month-old mice fed a ketogenic diet. We observed clear activation of inflammation and complement system pathways in the 26-month-old mice relative to the younger animals. Interestingly, ketogenic diet caused a modest but significant increase in the expression of SOX2-dependent oligodendrocyte/myelination markers.
Identification of a CCG-enriched expanded allele in DM1 patients using Amplification-free long-read sequencing
Authors: Tsai Yu-Chi , de Pontual Laure , Heiner Cheryl , Stojkovic Tanya , Furling Denis , Bassez Guillaume , Gourdon Geneviève , Tomé Stéphanie 
Published: February 2022

AbstractMyotonic dystrophy type 1 (DM1) exhibits highly heterogeneous clinical manifestations caused by an unstable CTG repeat expansion reaching up to 4,000 CTG. The clinical variability depends on CTG repeat number, CNG repeat interruptions and somatic mosaicism. Currently, none of these factors are simultaneously and accurately determined due to the limitations of gold standard methods used in clinical and research laboratories. An amplicon method for targeting DM1 locus using Single-Molecule Real-Time sequencing was recently developed to accurately analyze expanded alleles. However, amplicon-based sequencing still depends on PCR and the inherent bias towards preferential amplification of smaller repeats can be problematic in DM1. Thus, an amplification-free long-read sequencing method was developed using the CRISPR/Cas9 technology in DM1. This method was used to sequence the DM1 locus in patients with CTG repeat expansion ranging from 130 to > 1000 CTG. We showed that elimination of PCR amplification improves the accuracy of measurement of inherited repeat number and somatic repeat variations, two important key factors in the DM1 severity and age at onset. For the first time, an expansion composed of over 85% CCG repeats was identified using this innovative method in a DM1 family with an atypical clinical profile. No-Amplification targeted sequencing represents a promising method that can overcome research and diagnosis shortcomings, with translational implications for clinical and genetic counseling in DM1.
Egg-laying by female Aedes aegypti shapes the bacterial communities of breeding sites
Authors: Mosquera Katherine D. , Martínez Villegas Luis Eduardo , Fernandes Gabriel Rocha , David Mariana Rocha , Maciel-de-Freitas Rafael , Moreira Luciano A. , Lorenzo Marcelo G. 
Published: February 2022

ABSTRACTAedes aegypti, the main vector of multiple arboviruses, is highly associated with human dwellings. Females exhibit an opportunistic oviposition behavior, seldomly laying eggs on natural containers, but rather distributing them among human-generated breeding sites. Bacterial communities associated with such sites, as well as the compositional shifts they undergo through the development of larval stages, have been described. Some bacteria can play a direct role in supporting the success of mosquito development. Additionally, exposure to different bacteria during larval phases can have an impact on life-history traits. Whether the larvae acquire symbionts from aquatic niches, or just require bacteria as food, is still debated. Based on these facts, we hypothesized that female Ae. aegypti shape the bacterial communities of breeding sites during oviposition as a form of niche construction to favor offspring fitness. Our study presents a series of experiments to address whether gravid females modify bacterial consortia present in larval habitats. For this, we first verified if females can mechanically transfer bacteria into culture media. As evidence of mechanical transmission was obtained, we then elaborated an experimental scheme to dissect effects from factors related to the act of oviposition and mosquito-egg-water interactions. The DNA samples obtained from breeding site water belonging to five treatments were subjected to amplicon-oriented sequencing to infer their bacterial community structure. Microbial ecology analyses revealed significant differences between treatments in terms of diversity. Particularly, between-treatment shifts in abundance profiles were detected, also showing that females induce a significant decrease in alpha diversity through oviposition. In addition, indicator species analysis pinpointed bacterial taxa with significant predicting values and fidelity coefficients for the samples in which single females laid eggs. Furthermore, we provide evidence regarding how one of these indicator taxa, Elizabethkingia, exerts a positive effect upon the development and fitness of mosquito larvae, thus suggesting that the developmental niche construction hypothesis may hold in this model.
Experimental study on corrosion of 20# steel in oil-water stratified liquids based on wire beam electrode technique
Authors: Kou Jie , Ma Dongxu , Yang Le 
Published: February 2022

Purpose
Oil-water two-phase flow is the most prevalent medium in oil field gathering pipelines, and the corrosion of pipelines is often highly localized. Therefore, the purpose of this paper is to investigate the corrosion behavior of 20# pipeline steel in the oil-water stratified liquids, vary the water content of the upper emulsion and study the difference of the corrosion process.

Design/methodology/approach
Combine the wire beam electrodes (WBE) technique and the corrosion weight loss method to investigate the corrosion behavior of 20# steel in produced water simulation fluid and oil-water stratified liquids, and a corrosion mechanism model was established for analysis and explanation.

Findings
The results of mass loss experiments showed that the average corrosion rate increased with the increase in the water content of the upper emulsion. The corrosion current distribution maps indicated that the most serious corrosion occurred in the produced water simulation liquid, and the corrosion process showed the law of waterline corrosion. In addition, it was also found that the corrosion of the WBE in the stratified liquids had obvious non-uniformities. The electrode wires at the oil-water interface suffered from severe corrosion, caused by the dissolution of crude oil acids in water and the uneven distribution of oxygen in the corrosive medium.

Originality/value
The WBE technique provides a deep insight into the corrosion phenomena at the oil-water interface, which is helpful for characterization of the non-uniformity of corrosion parameters and evaluating the risks of multiphase corrosive media.
Employee emotional intelligence, organizational citizen behavior and job performance: a moderated mediation model investigation
Authors: Liao Shu-Hsien , Hu Da-Chian , Huang Yi-Ching 
Published: February 2022

PurposeEmotional intelligence (EI) affect behavior and thinking patterns are linked to physical and mental health, employee interpersonal relationships and job performance. Regarding individual EI, workplace employees expect high organizational support with positive employee relations, because they regard employee relations as a perceived support from the organization, which reflects a positive organization's citizenship behavior. Thus, in terms of human resource management, enhancing organizational citizen behavior can ensure that employees continue to improve job performance by maintaining a positive psychological state and employee relations.Design/methodology/approachUsing a questionnaire survey and structural equation modeling, this study aims to investigate the relationships between EI, psychological capital, job performance, organizational citizenship behavior (OCB) and perceived organizational support. The research subjects (N = 536) were in life insurance companies in Taiwan.FindingsThe results showed that psychological capital plays a mediating role in the effect of EI on OCB. Perceived organizational support is used to determine the existence of the effect of moderated mediation in the proposed research model.Originality/valueThis is the first study to find that the indirect effect of EI on organizational citizen behavior through psychological capital is stronger when there are higher levels of perceived organizational support than when there are lower levels of perceived organizational support. In addition, in terms of employee relation development, employee perceived organizational support from organizations is a critical influence which bridges employees' EI and organizational citizen behavior through psychological capital on the human resource management.
Vulnerability assessment of Balikpapan (Indonesia) for climate change-induced urban flooding
Authors: Ariyaningsih   , Sukhwani Vibhas , Shaw Rajib 
Published: February 2022

PurposeThe purpose of this paper is to examine the inter- and intra-relationships between climate change and urban flood risk in Balikpapan city.Design/methodology/approachThis study adopts a qualitative method by applying the driver–pressure–state–impact–response (DPSIR) framework, which helps to determine the strategies for reducing flood vulnerability in response to drivers, pressures, states and impacts. A secondary survey was conducted to understand the DPSIR.FindingsThe key drivers are identified as the population growth, land-use change, climate change and urbanization. Secondary data show that population growth due to urbanization in Balikpapan city is very high, which means that there is a lot of demand for land in the city, and the city’s current responses are mostly focused on building flood control and prevention infrastructures like detention ponds, zero Q technology policies and green open space. The study reveals that the responses that have been implemented in Balikpapan are mostly ineffective problem-solving, which cannot reduce vulnerability to flooding for the long term.Originality/valueTo the author’s knowledge, this is the first instance of the DPSIR framework being applied to Balikpapan city. It is, therefore, hoped that the study results will provide feasible directions to the city government for managing the future flood risks
Obtaining the effects of unobservable firm-specific characteristics on cost stickiness by the one-way error component regression model
Authors: Shirzad Ali 
Published: February 2022

Purpose
This research attempts to obtain the effect of unobservable firm-specific characteristics on selling, general and administrative (SG&A) cost stickiness by using panel data.

Design/methodology/approach
For this purpose, first, the authors describe the one-way error component regression model in panel data and presented that unobservable individual effect how could be estimated. Then the authors tested this panel data’s ability by estimating the effect of unobservable firm-specific characteristics on SG&A stickiness.

Findings
The authors find, for 195 firm-year of the industrial sector over 5 years, the SG&A costs increase on average at a rate of 0.76% per 1% increase in sales but decrease only 0.51% per 1% decrease in sales. In addition, the authors find that the unobservable characteristics of each company have different effects on SG&A cost stickiness.

Originality/value
As the present study is the pioneer study on describe the one-way error component regression model in panel data and presented the unobservable individual effects. The findings of this study can contribute to the realm of this study and the related literature.
The impact of anxiety levels on destination visit intention in the context of COVID-19: the mediating role of travel intention
Authors: Şengel Ümit , Genç Gökhan , Işkın Merve , Çevrimkaya Mustafa , Zengin Burhanettin , Sarıışık Mehmet 
Published: February 2022

PurposeThis study aims to investigate the effect of tourists' anxiety levels regarding pandemic on their intention to travel and intention to destination visit as a reflection of risk perception.Design/methodology/approachThis study employed a quantitative research design. Multivariate statistical methods were used because they predict cause and effect relationships. The data collection process was completed in 32 days between March 20 and April 20, 2020. Smart-PLS software was used for data analysis.FindingsAccording to the study results, the level of concern tourists have about the COVID-19 outbreak directly affected their intention to travel and indirectly affected their intention to visit destinations.Research limitations/implicationsAccording to the results of the study, people's anxiety levels about COVID-19 will negatively affect their travel behavior after the pandemic. Such results suggest that when potential travelers' pandemic-induced anxiety levels increase, their travel intention after the pandemic will decrease. In addition, there is a positive relationship between people's intention to travel and post-COVID-19 touristic visit intentions. Therefore, as people's travel intentions increase, so do their destination visit intentions. Another important theoretical implication of this research is that people's pandemic-induced anxiety levels have been shown to negatively affect their destination visit intention through the mediating variable of travel intention.Practical implicationsA multidimensional and stakeholder engagement process needs to be followed to decrease the influences of the pandemic on destinations. Destination management organizations (DMOs) can take an active role in crisis periods to encourage stakeholder participation while attracting tourism demand in the post-COVID-19 era.Originality/valueThis study is important for its topical relevance and for providing specific theoretical and practical implications concerning tourists' travel behavior.
Assessing the impact of ICT adoption on residents' self-rated health: evidence from China
Authors: Zhong Shunbin , Shen Xiaohua , Shen Weiteng , Xin Chongchong 
Published: February 2022

PurposeUtilizing data from the 2017 Chinese General Social Survey (CGSS2017), the paper aims to investigate the impact of information and communication technology (ICT) adoption on residents' self-rated health and reveals the mechanisms behind ICT.Design/methodology/approachIn the study, ICT adoption is defined as a dummy variable, which takes the value of one if respondents adopt the computers or mobile phone. Meanwhile, respondents' perceptions on five categories of self-rated health are used to construct the dependent variable. Then, based on a fixed-effects regression model, the ordinary least squares (OLS) and ordered probit approaches are applied to estimate their association. Moreover, the two-stage least squares (2SLS) and instrumental variable (IV)-oprobit methods are used to tackle the potential endogeneity of ICT adoption. Finally, the heterogeneity across individuals and regions as well as the underlying mechanisms are discussed.FindingsThe results indicate that ICT adoption significantly improves residents' self-rated health, which confirms the health utility model with ICT adoption. The conclusion is robust after overcoming the endogeneity issues with IV. In addition, heterogeneity analysis shows that ICT adoption is more beneficial to the health of residents who are male, young, better educated and those who live in the rural areas and in central and western China. Furthermore, the study demonstrates that ICT adoption for searching health-related information and improving social capital are two crucial mechanisms underlying its health effects.Practical implicationsThe findings of this research can help Chinese Government improve population health by issuing corresponding digital and health policies at the regional and individual level.Originality/valueFirst, the study provides fresh microscopic evidence on health outcomes of ICT adoption based on data from the latest wave of CGSS2017. Second, individual and regional heterogeneity is extensively discussed in contrast to most related macro studies that consider average effects. Third, the study addresses underlying mechanisms that have not been thoroughly tested or studied primarily on a theoretical level.