bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUMOylation of GMFB regulates the stability and function of GMFB in RPE cells under oxidative stress and inflammation
Authors: Sun Wan , Wang Juan , Zhang Jieping , Gao Furong , Ou Qingjian , Tian Haibin , Jin Caixia , Xu Jingying , Zhang Jingfa , huang Jian , Xu Guo-Tong , Lu Lixia 
Published: March 2021

AbstractGlia maturation factor beta (GMFB) is a growth and differentiation factor that act as an intracellular regulator of signal transduction pathways. The SUMOylation is a post-translational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. But little is known about the relationship between GMFB and SUMOylation. Here we first report that GMFB can be mono-SUMOylated at multiple sites by the covalent addition of a single SUMO1 protein, and identified K20, K35, K58, and K97 as major SUMO acceptor sites. We also found that SUMOylation leading to increased stability and trans-localization of GMFB. Furthermore, RNA-seq data and Real-time quantitative polymerase chain reaction (rt-qPCR) also indicated that the SUMOylated GMFB upregulated multiple pathways, including the cytokine-cytokin receptor interaction, NOD-like receptor signaling pathway, TNF signaling pathway, RIG-I-like receptor signaling pathway, and NF-kappa B signaling pathway. Our studies intend to provide a novel direction for the study into the biofunction of GMFB, SUMOylated GMFB and the mechanism, clinical therapy, and prognosis of inflammation-related RPE disorders like age-related macular degeneration (AMD) and diabetic retinopathy (DR).
Towards high spatially resolved microproteomics using expansion microscopy
Authors: Drelich Lauranne , Aboulouard Soulaimane , Franck Julien , Salzet Michel , Fournier Isabelle , Wisztorski Maxence 
Published: March 2021

AbstractExpansion microscopy is an emerging approach for morphological examination of biological specimens at nanoscale resolution using conventional optical microscopy. To achieve physical separation of cell structures, tissues are embedded in a swellable polymer and expanded several folds in an isotropic manner. This work shows the development and optimization of physical tissue expansion as a new method for spatially resolved large scale proteomics. Herein, we established a novel method to enlarge the tissue section to be compatible with manual microdissection on regions of interest and to carry out MS-based proteomic analysis. A major issue in the Expansion microscopy is the loss of proteins information during the mechanical homogenization phase due to the use of Proteinase K. For isotropic expansion, different homogenization agents are investigated, both to maximize protein identification and to minimize protein diffusion. Better results are obtained with SDS. From a tissue section enlarge more than 3-fold, we have been able to manually cut out regions of 1mm in size, equivalent to 300µm in their real size. We identified up to 655 proteins from a region corresponding to an average of 940 cells. This approach can be performed easily without any expensive sampling instrument. We demonstrated the compatibility of sample preparation for expansion microscopy and proteomic study in a spatial context.Abstract graphic
Emergence of function from single RNA sequences by Darwinian evolution
Authors: Wachowius Falk , Porebski Benjamin T. , Johnson Christopher M. , Holliger Philipp 
Published: March 2021

AbstractThe spontaneous emergence of function from pools of random sequence RNA is widely considered an important transition in the origin of life. However, the plausibility of this hypothetical process and the number of productive evolutionary trajectories in sequence space are unknown. Here we demonstrate that function can arise starting from a single RNA sequence by an iterative process of mutation and selection. Specifically, we describe the discovery of both specific ATP or GTP aptamers - with micromolar affinity for their nucleotide ligand - starting each from a single, homopolymeric poly-A sequence flanked by conserved primer binding sites. Our results indicate that theab initiopresence of large, diverse random sequence pools is not a prerequisite for the emergence of functional RNAs and that the process of Darwinian evolution has the capacity to generate function even from single, largely unstructured RNA sequences with minimal molecular and informational complexity.
Bi-directional protein-protein interactions control liquid-liquid phase separation of PSD-95 and its interaction partners
Authors: Christensen Nikolaj Riis , Pedersen Christian Parsbæk , Sereikaite Vita , Pedersen Jannik Nedergaard , Vistrup-Parry Maria , Sørensen Andreas Toft , Otzen Daniel , Arleth Lise , Teilum Kaare , Madsen Kenneth L. , Strømgaard Kristian 
Published: March 2021

SUMMARYThe organization of the postsynaptic density (PSD), a protein-dense semi-membraneless organelle, is mediated by numerous specific protein-protein interactions (PPIs) which constitute a functional post-synapse. Postsynaptic density protein 95 (PSD-95) interacts with a manifold of proteins, including the C-terminal of transmembrane AMPA receptor (AMAPR) regulatory proteins (TARPs). Here, we uncover the minimal essential peptide responsible for the stargazin (TARP-γ2) mediated liquid-liquid phase separation (LLPS) formation of PSD-95 and other key protein constituents of the PSD. Furthermore, we find that pharmacological inhibitors of PSD-95 can facilitate formation of LLPS. We found that in some cases LLPS formation is dependent on multivalent interactions while in other cases short peptides carrying a high charge are sufficient to promote LLPS in complex systems. This study offers a new perspective on PSD-95 interactions and their role in LLPS formation, while also considering the role of affinity over multivalency in LLPS systems.
Patterns of gene content and co-occurrence constrain the evolutionary path toward animal association in CPR bacteria
Authors: Jaffe Alexander L. , He Christine , Keren Ray , Valentin-Alvarado Luis E. , Munk Patrick , Bouma-Gregson Keith , Farag Ibrahim F. , Amano Yuki , Sachdeva Rohan , West Patrick T. , Banfield Jillian F. 
Published: March 2021

ABSTRACTCandidate Phyla Radiation (CPR) bacteria are small, likely episymbiotic organisms found across Earth’s ecosystems. Despite their prevalence, the distribution of CPR lineages across habitats and the genomic signatures of transitions amongst these habitats remain unclear. Here, we expand the genome inventory for Absconditabacteria (SR1), Gracilibacteria, and Saccharibacteria (TM7), CPR bacteria known to occur in both animal-associated and environmental microbiomes, and investigate variation in gene content with habitat of origin. By overlaying phylogeny with habitat information, we show that bacteria from these three lineages have undergone multiple transitions from environmental habitats into animal microbiomes. Based on co-occurrence analyses of hundreds of metagenomes, we extend the prior suggestion that certain Saccharibacteria have broad bacterial host ranges and constrain possible host relationships for Absconditabacteria and Gracilibacteria. Full-proteome analyses show that animal-associated Saccharibacteria have smaller gene repertoires than their environmental counterparts and are enriched in numerous protein families, including those likely functioning in amino acid metabolism, phage defense, and detoxification of peroxide. In contrast, some freshwater Saccharibacteria encode a putative rhodopsin. For protein families exhibiting the clearest patterns of differential habitat distribution, we compared protein and species phylogenies to estimate the incidence of lateral gene transfer and genomic loss occurring over the species tree. These analyses suggest that habitat transitions were likely not accompanied by large transfer or loss events, but rather were associated with continuous proteome remodeling. Thus, we speculate that CPR habitat transitions were driven largely by availability of suitable host taxa, and were reinforced by acquisition and loss of some capacities.IMPORTANCEStudying the genetic differences between related microorganisms from different environment types can indicate factors associated with their movement among habitats. This is particularly interesting for bacteria from the Candidate Phyla Radiation because their minimal metabolic capabilities require symbiotic associations with microbial hosts. We found that shifts of Absconditabacteria, Gracilibacteria, and Saccharibacteria between environmental ecosystems and mammalian mouths/guts probably did not involve major episodes of gene gain and loss; rather, gradual genomic change likely followed habitat migration. The results inform our understanding of how little-known microorganisms establish in the human microbiota where they may ultimately impact health.
LCK Regulates Homologous Recombination DNA Repair Identifying a New Target for Sensitizing PARP Inhibitors in HR Proficient Ovarian Cancer
Authors: Dey Goutam , Bharti Rashmi , Braley Chad , Alluri Ravi , Esakov Emily , Crean-Tate Katie , McCrae Keith , Joehlin-Price Amy , Rose Peter G. , Lathia Justin , Gong Zihua , Reizes Ofer 
Published: March 2021

AbstractPoly-ADP Ribose Polymerase (PARP) targeted therapy is clinically approved for the treatment of homologous recombination (HR) repair deficient tumors. The remarkable success in treatment of HR repair deficient cancers has not translated to HR-proficient cancer. Our studies identify the mechanism of non-receptor lymphocyte-specific protein tyrosine kinase (LCK) in HR repair in endometrioid epithelial ovarian cancer (eEOC). LCK expression is induced and activation in the nucleus in response to DNA damage insult. LCK inhibition attenuates expression of RAD51, BRCA1, and BRCA2 proteins necessary for HR-mediated DNA repair, sufficient to suppress RAD51 foci formation, and augments γH2AX foci formation. Mechanistically, DNA damage leads to direct interaction of LCK with RAD51 and BRCA1 in a kinase dependent manner. Attenuation of LCK sensitized HR-proficient eEOC cells to PARP inhibitor in cell culture and pre-clinical mouse studies. These findings identify a new mechanism for expanding utility of PARP inhibitors in HR proficient ovarian cancer.Graphical Abstract
Autism-associated CHD8 keeps proliferation of human neural progenitors in check by lengthening the G1 phase of the cell cycle
Authors: Coakley-Youngs Emma , Shorter Susan , Ranatunga Medhavi , Richardson Simon , Getti Giulia , Fivaz Marc 
Published: March 2021

AbstractCHD8 (Chromodomain Helicase DNA Binding Protein 8) is a chromatin remodeler that preferentially regulates expression of genes implicated in early development of the cerebral cortex.De novomutations (DNMs) in CHD8 are strongly associated with a specific subtype of autism characterized by enlarged foreheads and distinct cranial features. The vast majority of these DNMs are heterozygous loss-of-function mutations with high penetrance for autism. HowCHD8haploinsufficiency alters the normal developmental trajectory of the human cortex is poorly understood and debated. Previous studies in the mammalian developing cortex have shown progressive lengthening of the G1 phase of the cell cycle as neural stem cells transition from proliferative to neurogenic divisions. G1 length has been proposed to operate as a molecular clock that controls timing of this crucial developmental switch. To determine the influence of CHD8 on cell cycle timing, we disrupted one allele ofCHD8in human embryonic stem cells (hESCs), differentiated these cells into neural precursor cells (NPCs), and imaged cell cycle progression of individualCHD8+/−NPCs — in parallel with their isogenicCHD8+/+counterparts — during several rounds of cell division. We found a specific and marked decrease in G1 duration inCHD8+/−NPCs, resulting in an overall shortening of the cell cycle. Consistent with faster progression ofCHD8+/−NPCs through G1 and the G1/S checkpoint, we observed increased expression of E cyclins and elevated phosphorylation of Erk in these mutant cells — two central signalling pathways involved in S phase entry. Together, our findings show dysregulated proliferation of NPCs in a human stem cell model ofCHD8haploinsufficiency and predict enlargement of the neural progenitor pool inCHD8+/−developing brains, a phenotype that may explain macrocephaly in individuals withCHD8DNMs. Furthermore, our work provides further evidence for a link between autism and cancer and identifies MAPK signaling as a potential therapeutic target for the treatment of this autism subtype.
Offsite construction skills evolution: an Australian case study
Authors: Ginigaddara Buddhini , Perera Srinath , Feng Yingbin , Rahnamayiezekavat Payam 
Published: March 2021

Purpose
The construction industry is currently responding to pressures of industrialisation happening across all sectors. Consequently, offsite construction (OSC) has become a vehicle to achieve industrialisation. This requires changes in traditional construction processes resulting in possible changes in construction skill requirements. Accordingly, the purpose of this study is to identify and review prevailing OSC practices and skills in the Australian construction industry. This study aims to critically analyse the existing skill profile classifications through a single case study and identify the need for an OSC specific skill classification.

Design/methodology/approach
This study follows a case study design, with an in-depth analysis of a single construction project. Only one case study was studied because scientifically, one example was enough to prove that the prevailing skill classifications do not represent OSC skills in a modern context. Data was retrospectively collected through semi-structured interviews of project stakeholders representing design, manufacture and assembly. Content analysis was conducted to analyse the collected data and produce findings.

Findings
This study identifies the inadequacy of the existing classification system, unavailability and the need of OSC specific skill categorisation. It highlights new skills that enter OSC; building information modelling engineer, three-dimensional draftsperson, OSC project manager and project coordinator, which are not identified in the available Australian skill classifications. These, together with existing skills need to be carved in to create a new skill classification.

Originality/value
This study is the first of its kind where a comprehensive OSC project is evaluated as a case study to determine OSC skill classification requirements in Australia.
Configuration analysis of influencing factors of operating efficiency based on fsQCA: evidence from China’s property insurance industry
Authors: Li Zhiguang , Li Yaokuang , Zhang Wei 
Published: March 2021

PurposeBased on the perspective of complexity theory, the operation process of property insurance companies can be regarded as a complex dynamic nonlinear chaotic system. This paper aims to measure the operating efficiency of 29 Chinese domestic property and casualty (P&C) companies and 18 foreign-invested P&C companies from 2011 to 2017 and outline the path to achieving high-quality development.Design/methodology/approachThe data were obtained from the Chinese Insurance Yearbook and China Statistical Yearbook 2012–2018. The data envelopment analysis method was used to calculate the technical efficiency of property insurance companies and fuzzy set qualitative comparative analysis is used for configuration analysis of determinants affecting technical efficiency.FindingsThis paper founds the average technical efficiency of Chinese domestic P&C insurance companies was 0.914 and that of foreign-invested P&C insurance companies was 0.895. The average total factor productivity of Chinese domestic P&C insurance companies was 1.058 and that of foreign-invested P&C insurance companies was 1.051. There were three modes to improve the company’s technical efficiency, with high loss ratio and low reinsurance ratio, poor employee education and higher leverage ratio and high leverage ratio and low reinsurance ratio as the core conditions.Originality/valueThis study puts forward four applicable, targeted and proven ways to improve the technical efficiency of China’s P&C insurance industry. These configurations were verified by the cases of existing property insurance companies, which can provide practical references for the insurance industry.
Strategies to mitigate the impact of COVID-19 on supply chain disruptions: a multiple case analysis of buyers and distributors
Authors: Butt Atif Saleem 
Published: March 2021

PurposeThis paper explores the steps/countermeasures taken by buying and distributing firms to address supply chain disruptions caused by COVID-19.Design/methodology/approachThis study employs a multiple case study methodology and conducts 36 semi-structured interviews with senior managers of nine different firms producing, procuring or distributing products from China and other highly impacted South Asian regions (Pakistan, Sri Lanka, India).FindingsResults reveal that buying firms are moving to agile production, focusing on tier-1 supplier risk, enhancing inbound material visibility and temporarily closing production facilities to respond to the challenges posed by COVID-19. Furthermore, distribution centres are modifying their inventory policies, evaluating alternative outbound routes and sources of supply to manage disruptions caused to their business operations amid COVID-19 outbreak.Practical implicationsSupply chain firms can use the countermeasures provided in this study to mitigate the impact of COVID-19 and make the best out of this pandemic.Originality/valueThis study contributes to the supply chain literature by exploring the countermeasures taken by firms to mitigate the impact of COVID-19. In particular, this study explores such countermeasures from the perspective of two different entities (buyers and distributors) along the supply chain. Firms can use the countermeasures highlighted in this study to mitigate the impact of COVID-19 on the supply chain.
Role of ICT in emancipation of digital entrepreneurship among new generation women
Authors: Shukla Anuja , Kushwah Priyanka , Jain Eti , Sharma Shiv Kumar 
Published: March 2021

Purpose
The role of information and communications technology (ICT) has been tested in various contexts of online shopping and the results show that ICT has successfully transformed the way of doing business. This study aims to propose that if women have adequate internet skills, namely, operative, informational and creative skills, their entrepreneurial intentions will be high.

Design/methodology/approach
This is descriptive research. The data was collected from 246 university students and analyzed using PLS-SEM.

Findings
The results of the study show that students belonging to entrepreneurial backgrounds have a positive attitude toward entrepreneurship. The impact of internet skills was mixed on the relationship of entrepreneurial attitude and entrepreneurial intention.

Research limitations/implications
The sample was not generalized as the sample consisted of urban and internet-using women. Future research can test the model for rural women entrepreneurs or usage of m-commerce for the same.

Practical implications
The results of the study show that women having the skills to operate the internet have higher intentions to become an entrepreneur. Thus, the e-commerce web-space can use the results to influence women of the new generation to use available tools in their journey of entrepreneurship.

Social implications
Women are an indispensable part of society. Empowering them will not only improve their confidence but will also strengthen the pillars of society.

Originality/value
Extensive research work has been done in the context of women entrepreneurship. The study is a novel attempt to test the effects of internet skills on entrepreneurial intention among new generation women. The results will be very much useful for future research and will extend the body of academic literature.
Fraud in higher education: a system for detection and prevention
Authors: de Souza-Daw Tony , Ross Robert 
Published: March 2021

Purpose
Academic corruption and fraudulent practices have become problematic in recent years. Governments around the world have introduced dedicated higher education commissions to regulate higher education providers. The purpose of this paper is to design a system for the detection and prevention framework of fraudulent behaviour in higher education.

Design/methodology/approach
This paper performs a survey on academic misconduct practices and expands the survey by analysing the accreditation process. This study further identifies common corrupt practices in the accreditation process with reference to particular accreditation standards or laws. If the accreditation process is as thorough as, this paper is led to believe, a higher institute may stop being compliant immediately after the accreditation process. playing a catch-me-if-you-can at the next accreditation cycle. The survey of the accreditation process and identification of corrupt practices lead to an identification of preventative and detective measures.

Findings
The review of accreditation procedures and conditions identifies that fraudulent practices can occur at every part of any policy and procedure. The framework prevents repudiation and allows for spontaneous investigations internally and externally. The blockchain prevented changes to the system and allow for auditing of changes. A system such as this could suppress accreditation fraud and minimise its corrupt impact. Not to mention identify with relative ease the severity and life of corrupt practice.

Originality/value
Contributions are made in the framework for detecting and preventing corrupt practices in Higher Education using blockchain immutable transactions. This enables real-time accreditation compliance checks and monitoring of conditions. External complaints or reviews can be conducted with minimum interactions from higher education providers.
The relationship between financial development and effectiveness of monetary policy: new evidence from ASEAN-3 countries
Authors: Abdul Karim Zulkefly , Kamal Basa Danie Eirieswanty , Abdul Karim Bakri 
Published: March 2021

PurposeThis paper aims to investigate the relationship between financial development (FD) and monetary policy effectiveness (MPE) on output and inflation in ASEAN-3 countries (Singapore, Malaysia and the Philippines).Design/methodology/approachThis study uses an open economy structural vector autoregressive model to generate MPE. Then, an autoregressive distributed lagged (ARDL) model is used to analyze the effect of FD on MPE across countries.FindingsThe findings revealed that FD plays a different role in MPE across countries. In Malaysia, a more developed financial system tends to reduce the MPE on output, whereas in Singapore, results show that the more developed financial system (stock market capitalization) tends to increase MPE on output. However, in the Philippines, the main results show that the effect of FD (liquid liabilities) upon MPE on output is depending on the policy variable (interest rates or money supply).Originality/valueThis paper fills this gap by providing the first study of ASEAN-3 countries in examining how effective is a monetary policy in response to the development of the financial market across the country. Second, this paper considers two FD indicators, namely, the banking sector and capital market development in investigating its effect on MPE on output and inflation. Third, the authors construct the MPE in each country using a structural (identified) VAR model by aggregating the response of output growth and inflation rate on monetary policy changes (interest rate and money supply) using impulse–response function. Regarding this, the results of this study provide new empirical evidence and insight into the long debate on the relationship between FD and the MPE.