bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution Nanopore methylome-maps reveal random hyper-methylation at CpG-poor regions as driver of chemoresistance in leukemias
Authors: Magi Alberto , Mattei Gianluca , Mingrino Alessandra , Caprioli Chiara , Ronchini Chiara , Frigè GianMaria , Semeraro Roberto , Bolognini Davide , Rambaldi Alessandro , Candoni Anna , Colombo Emanuela , Mazzarella Luca , Pelicci Pier Giuseppe 
Published: October 2022

AbstractAberrant DNA methylation at CpG dinucleotides is a hallmark of cancer and is associated with the emergence of resistance to anti cancer treatment, though molecular mechanisms and biological significance remain elusive. Genome scale methylation maps by currently used methods are based on chemical modification of DNA and are best suited for analyses of methylation at CpG rich regions (CpG islands). We report the first high coverage whole genome map in cancer using the long read nanopore technology, which allows simultaneous DNA-sequence and -methylation analyses on native DNA. We analyzed clonal epigenomic/genomic evolution in Acute Myeloid Leukemias (AMLs) at diagnosis and relapse, after chemotherapy. Long read sequencing coupled to a novel computational method allowed definition of differential methylation at unprecedented resolution, and showed that the relapse methylome is characterized by hypermethylation at both CpG islands and sparse CpGs regions. Most differentially methylated genes, however, were not differentially expressed nor enriched for chemoresistance genes. A small fraction of under-expressed and hyper-methylated genes at sparse CpGs, in the gene body, was significantly enriched in transcription factors (TFs). Remarkably, these few TFs supported large gene-regulatory networks including 50% of all differentially expressed genes in the relapsed AMLs and highly-enriched in chemoresistance genes. Notably, hypermethylated regions at sparse CpGs were poorly conserved in the relapsed AMLs, under-represented at their genomic positions and showed higher methylation entropy, as compared to CpG islands. Relapsed AMLs carried few patient specific structural variants and DNA mutations, apparently not involved in drug resistance. Thus, drug resistance in AMLs can be mainly ascribed to the selection of random epigenetic alterations at sparse CpGs of a few transcription factors, which then induce reprogramming of the relapsing phenotype, independently of clonal genomic evolution.
How a tarantula can help treat infections:Avicularia juruensis’s theraphotoxins that also act as antimicrobials
Authors: do Nascimento Soraia Maria , Roa Andrea Díaz , Mendonça Ronaldo Zucatelli , da Silva Junior Pedro Ismael 
Published: October 2022

Short abstractConsidering that there are still many species little-studied, this work aimed to analyze the venom of the spiderAvicularia juruensissearching for antimicrobial peptides. Using reverse-phase high-performance liquid chromatography, microbial growth inhibition assay, transcriptomics, and proteomics approaches we identified three antimicrobial peptides: Avilin, Juruin_2, and Juruenine. All of them showed similarities with neurotoxins that act on ion channels and, probably, they have the ICK motif. The study of animal venoms is of great importance to carry out the characterization of unknown components and that may have a biotechnological application, in special venoms from spiders that are from less studied families.Spiders are the most successful group of venomous animals, comprising more than 50,350 species distributed in all terrestrial habitats. One strategy that facility their broad distribution is the production of elaborate venoms, which are composed of inorganic salts, organic molecules with low molecular mass, free amino acids, small polypeptides, linear peptides, nucleotides, disulfide-rich peptides, enzymes, and high molecular mass proteins. Considering that there are still many species little-studied, this work aimed to analyze the venom of the mygalomorph spiderAvicularia juruensissearching for new antimicrobial peptides. Using reverse-phase high-performance liquid chromatography, microbial growth inhibition assay, transcriptomics, and proteomics approaches we identified three antimicrobial peptides that were named Avilin, Juruin_2, and Juruenine. All of them showed similarities with neurotoxins that act on ion channels and, probably, they have the ICK motif in their structure. The ICK fold seems to be conserved in several venomous animal lineages and presents elevated functional diversity, as well as gives stability to the toxins. The study of animal venoms is of great importance to carry out the characterization of unknown components and that may have a biotechnological application (like the antimicrobial peptides), in special venoms from spiders that are from less studied families.
7q11.23 CNV alters protein synthesis and REST-mediated neuronal intrinsic excitability
Authors: Mihailovich Marija , Germain Pierre-Luc , Shyti Reinald , Pozzi Davide , Noberini Roberta , Liu Yansheng , Aprile Davide , Tenderini Erika , Troglio Flavia , Trattaro Sebastiano , Fabris Sonia , Ciptasari Ummi , Rigoli Marco Tullio , Caporale Nicolò , D’Agostino Giuseppe , Vitriolo Alessandro , Capocefalo Daniele , Skaros Adrianos , Franchini Agnese , Ricciardi Sara , Biunno Ida , Neri Antonino , Kasri Nael Nadif , Bonaldi Tiziana , Aebersold Rudolf , Matteoli Michela , Testa Giuseppe 
Published: October 2022

AbstractCopy number variations (CNVs) at 7q11.23 cause Williams-Beuren (WBS) and 7q microduplication syndromes (7Dup), two neurodevelopmental disorders with shared and opposite cognitive-behavioral phenotypes. Using patient-derived and isogenic neurons, we integrated transcriptomics, translatomics and proteomics to elucidate the molecular underpinnings of this dosage effect. We found that 7q11.23 CNVs cause opposite alterations in neuronal differentiation and excitability. Genes related to neuronal transmission chiefly followed 7q11.23 dosage and appeared transcriptionally controlled, while translation and ribosomal protein genes followed the opposite trend and were post-transcriptionally buffered. Mechanistically, we uncovered REST regulon as a key mediator of observed phenotypes and rescued transcriptional and excitability alterations through REST inhibition. We identified downregulation of global protein synthesis, mGLUR5 and ERK-mTOR pathways activity in steady-state in both WBS and 7Dup, whereas BDNF stimulation rescued them specifically in 7Dup. Overall, we show that 7q11.23 CNVs alter protein synthesis and neuronal firing-established molecular and cellular phenotypes of neurodevelopmental disorders.Graphical abstract
Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band
Authors: Ortone Andrea , Vergani Alberto Arturo , Mannella Riccardo , Mazzoni Alberto 
Published: October 2022

AbstractMotor symptoms of Parkinson’s Disease (PD) are associated with dopamine deficits and pathological oscillation of basal ganglia (BG) neurons in theβrange ([12-30] Hz). However, how the dopamine depletion affects the oscillation dynamics of BG nuclei is still unclear. With a spiking neurons model, we here captured the features of BG nuclei interactions leading to oscillations in dopamine-depleted condition. We found that both the loop between subthalamic nucleus and Globus Pallidus pars externa (GPe) and the loop between striatal fast spiking and medium spiny neurons and GPe displayed resonances in theβrange, and synchronized to a commonβfrequency through interaction. Crucially, the synchronization depends on dopamine depletion: the two loops were largely independent for high levels of dopamine, but progressively synchronized as dopamine was depleted due to the increased strength of the striatal loop. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustainedβoscillations in PD subjects, and explain how this interplay depends on the level of dopamine. This paves the way to the design of therapies specifically addressing the onset of pathologicalβoscillations.Author summaryParkinson’s Disease is associated to the death of neurons generating a particular neurotransmitter: the dopamine. Motor symptoms of PD, on the other hand, are known to be due to dysfunctions in a particular subcortical area of the brain, the BG network. In particular, the BG network develops pathological oscillations in a specific frequency range (β: [12-30] Hz). What is unclear is how dopamine depletion leads to these oscillations. In this work we developed a BG network model and we found the actual reason for these abnormal oscillations is the synchronization of two loops within the network that are individually oscillating in theβrange. For healthy level of dopamine the two loops are decoupled and the oscillation power is low. When dopamine is depleted (as in PD) the two loops synchronize and originate the pathological oscillations associated with motor symptoms.
Autophagy in parvalbumin interneurons is required for inhibitory transmission and memory via regulation of synaptic proteostasis
Authors: Chalatsi Theodora , Fernandez Laura M.J. , Scholler Jules , Batti Laura , Kolaxi Angeliki , Restivo Leonardo , Lüthi Anita , Mameli Manuel , Nikoletopoulou Vassiliki 
Published: October 2022

SummaryWith the emerging role of the autophagic machinery in healthy brain development and aging, there is a pressing need to better characterize its functions in different neuronal populations, providing cellular insight into autophagy-related brain diseases. Here, we generated and characterized mice with conditional ablation ofatg5in GABAergic neurons expressing parvalbumin (PV-atg5KO), mostly comprising fast-spiking interneurons, as well as Purkinje cells in the cerebellum. Using light-sheet microscopy to image PV neurons throughout the brain, we reveal that autophagy is required for the sustenance of Purkinje cells but not of PV-interneurons. Yet, proteomic analysis showed that autophagy deficiency in cortical and hippocampal PV-interneurons alters the proteostasis of key synaptic proteins, as well as the surface expression of glutamate receptor subunits. Consistently, hippocampal autophagy-deficient PV-interneurons exhibit reduced inhibitory neurotransmission andPV-atg5KOmice display excitation-inhibition imbalance in the hippocampus and memory deficits. Our findings demonstrate a neuronal type-specific vulnerability to autophagy deficiency, while also identifying PV-interneurons as cellular substrates where autophagy is required for memory.
Chi-miR-3880 mediates the regulatory role of interferon gamma in goat mammary gland
Authors: Zhang Yue , Liu Jidan , Niu Guanglin , Wu Qiong , Cao Fangjun , Cao Binyun 
Published: October 2022

AbstractA healthy mammary gland is a necessity for milk production of dairy goats. The role of chi-miR-3880 in goat lactation is illustrated in our previous study. Among the differentially expressed genes regulated by chi-miR-3880, one seventh are interferon stimulated genes, includingMX1,MX2,IFIT3,IFI44L, andDDX58. As the inflammatory cytokine interferon gamma (IFNγ) has been identified as a potential marker of caseous lymphadenitis in lactating sheep, the interaction between IFNγ and immune-related microRNAs is explored. In this study, it was found that chi-miR-3880 could be one of the microRNAs downregulated by IFNγ in goat mammary epithelial cells (GMECs). The regulation among IFNγ, chi-miR-3880, andDDX58, as well as their roles in mammary gland were investigated. The study illustrated that IFNγ/chi-miR-3880/DDX58axis modulates GMEC proliferation and lipid formation through PI3K/AKT/mTOR pathway, and regulates apoptosis through Caspase-3 and Bcl-2/Bax. The role of the axis in involution was reflected by the expression of p53 and NF-κB. In conclusion, IFNγ/chi-miR-3880/DDX58axis plays an important part in lactation.
Union influence on change-oriented organizational citizenship behavior: evidence from China
Authors: Hu Enhua , Han Mingyan , Zhang Mengyue , Huang Lin , Shan Hongmei 
Published: October 2022

PurposeDespite the considerable research into China's industrial relation system, little attention has been focused on what do Chinese unions at the enterprise level do and how their daily work influences employees' work-related outcomes. Drawing on the theory of planned behavior, this paper aims to examine the impact of Chinese enterprise union practices on employees' change-oriented organizational citizenship behavior through the mediating roles of psychological safety, perceived insider status, and role breadth self-efficacy.Design/methodology/approachData were collected from 450 employees at 45 unionized enterprises in China through a three-wave survey. Multilevel analyses were conducted to test the hypothesized effects.FindingsChinese enterprise union practices positively predicted change-oriented organizational citizenship behavior. Critically, psychological safety and role breadth self-efficacy mediated the positive relationship between Chinese enterprise union practices and change-oriented organizational citizenship behavior.Originality/valueThis study provides new evidence on the effectiveness of Chinese enterprise union practices from a perspective of employees' work-related outcomes. It also enriches the existing literature on antecedents of change-oriented organizational citizenship behavior and provides a “planned” perspective to understand the mechanism that underlies the relationship between Chinese enterprise union practices and change-oriented organizational citizenship behavior.
Integration of Six Sigma and simulations in real production factory to improve performance – a case study analysis
Authors: Ahmed Ali , Olsen John , Page John 
Published: October 2022

Purpose
The overarching objective of this research is to integrate the Lean Six Sigma (LSS) framework with computer simulation to improve the production efficiency of a light-emitting diode (LED) manufacturing factory.

Design/methodology/approach
Recently, the idea of taking advantage of the benefits of Six Sigma and simulation models together has led both industry and the academy towards further investigation and implementation of these methodologies. From this perspective, the present research will illustrate the effectiveness of using LSS methodology in a real factory environment by using the combination of three simulation methods which are system dynamics (SD), discrete-event simulation (DES) and agent-based (AB) modelling.

Findings
The hybrid simulation method applied in this research was found to accurately mimic and model the existing real factory environment. The define, measure, analyse, control and improve (DMAIC)-based improvements showed that the applied method is able to improve machine utilization rates while balancing the workload. Moreover, queue lengths for several stations were shortened, and the average processing time was decreased by around 50%. Also, a weekly production increase of 25% was achieved while lowering the cost per unit by around 8%.

Research limitations/implications
While the case study used was for a LED manufacturing system, the proposed framework could be implemented for any other existing production system. The research also meticulously presents the steps carried out for the development of the multi-method simulation model to allow readers to replicate the model and tailor it for their own case studies and projects. The hybrid model enables managers to navigate the trade-off decisions they often face when choosing advanced production output ahead of continuous improvement practices. The adoption of methodologies outlined in this paper would attain improvements in terms of queue lengths, utilization, reduced costs and improved quality and efficiency of a real, small factory. The findings suggest improvements and create awareness among practitioners for the utilization of quality tools that will provide direct benefits to their companies. Although the multi-method simulation is effective, a limitation of the current study is the lack of micro details within each station. Furthermore, the results are all based on one specific case study which is not enough to suggest and generalized findings.

Originality/value
This research combines the use of the three main hybrid simulation paradigms (SD, DES and AB) in a unified framework DMAIC methodology. Choosing the right models in DMAIC is important, challenging and urgently necessary. Also, this paper shows empirical evidence on its effectiveness.
From static to processual analysis: how insights from Austrian economics can advance research on public policy and entrepreneurship
Authors: Bylund Per L. , Packard Mark D. , Rapp David J. 
Published: October 2022

PurposeThe purpose of this paper is to illustrate how research on the intersection of public policy and entrepreneurship has been bounded by its static approach and how a processual analysis based on Austrian economics can advance the understanding of the subject matter.Design/methodology/approachRooted in the Austrian school of economics, this conceptual paper adopts a processual approach in order to unveil the effects that public policy exerts upon entrepreneurship and the market process.FindingsThe authors argue that by interfering with the market process, public policy detrimentally alters what otherwise would have been the market's natural evolution reflecting acting individuals' subjective valuations. It causes progressively self-reinforcing market distortions which result in comparatively lower levels of both capital accumulation and societal wealth.Research limitations/implicationsThe paper urges future research to rethink public policy's effects on entrepreneurship and to explore them more comprehensively, utilizing market process analysis.Practical implicationsThis research suggests that public policy can never be neutral but necessarily comes with distortive and often detrimental effects. That is, public policy comes at the innate expense of hampering the entrepreneurial process. Thus, new public policies and those already in place should be carefully reconsidered in light of these effects.Originality/valueThis paper offers a novel take on how to best understand the effects public policy has on entrepreneurship and the market process.
How can sustainability be effectively regulated?
Authors: Teichmann Fabian Maximilian Johannes , Wittmann Chiara 
Published: October 2022

Purpose
This paper aims to examine the fundamental conditions which are necessary for the construction of a regulation which will affect a genuine advancement in the context of environmental protection.

Design/methodology/approach
The component parts of an adequately built regulation are broken down to concretise the notion of efficacy – and its proposed universality – in a regulatory context. This paper takes a comparative approach of regulations and extends to include a consideration of the monitoring and enforcement of regulation as a necessary tenant of an effective regulation.

Findings
Sustainability regulations have seen a significant development in the 20th century. Notable remain the national discrepancies to so universal problem, as well as an inconsistent acknowledgement of the purpose of sustainability regulations beyond a tick-box compliance commitment.

Originality/value
The importance of sustainability has been amplified without a due consideration of what its translation into regulation must look like. This paper argues that no meaningful change can be lobbied without understanding how its practical implementation is performed.
Relative financial deprivation, financial anxiety and financial satisfaction: the role of access to Islamic financing among MSME owners amidst COVID-19
Authors: Mahmoud Mahmoud Ahmad , Umar Umar Habibu , Baita Abubakar Jamilu , Ado Muhammad Bilyaminu 
Published: October 2022

Purpose
The purpose of this paper is to augment the present literature on the relationship between relative financial deprivation (RFD), financial anxiety (FA), access to Islamic financing (AIF) and financial satisfaction (FS) of micro, small and medium enterprise (MSME) owners. Principally, the study examines the moderating role of AIF on the RFD–FS and FA–FS relationships.

Design/methodology/approach
Quantitative survey approach was used to collect data through self-administered questionnaires from MSME owners. Partial least square (PLS) structural equation modelling (SEM) version 3.2.7 was used to analyse 208 retrieved questionnaires.

Findings
The results confirm that the RFD–FS relationship is negatively significant, but the FA–FS relationship is not significant. However, the direct relationship between AIF and FS is positively significant. Conversely, AIF failed to moderate the RFD–FS and FA–FS relationships.

Practical implications
The study specifies that the existence of RFD will decrease the FS of MSME owners, and therefore, RFD should be eliminated at all costs. However, the greater the AIF, the stronger will be the FS of MSME owners. Thus, policymakers and owners of MSMEs should emphasize on AIF to foster FS. Nevertheless, AIF could not redirect the negative impact of RFD and FA on MSME owners’ FS.

Originality/value
This study, to the best of the authors’ knowledge, is the first to examine the moderating role of AIF on the RFD–FS and FA–FS relationships among MSME owners. Notwithstanding the importance of small business owners for economic development, the literature on MSME entrepreneurs FS has been neglected. This study also uncovers new theoretical knowledge by revealing the inability of AIF to alter the RFD–FS and FA–FS relationships.
Innovative strategies to tackle post-Covid-19 tourism: case of small tourism companies
Authors: Sharma Swati , Sharma Ankita 
Published: October 2022

Purpose
The Covid-19 pandemic adversely affected the tourism industry. The highly contagious coronavirus-19 has brought the whole industry to its knees, initiating catastrophic effects in terms of loss of jobs and revenue. The purpose of this qualitative study is to identify the innovative coping strategies adopted by small tourism companies (STCs) to revive business and cope with the pandemic.

Design/methodology/approach
This study used qualitative exploration and asked open-ended questions to senior executives of STCs in India. Written responses were obtained from the respondents. Thematic analysis was performed to analyse the responses of the participants.

Findings
The findings highlight the innovative strategies adopted by STCs to cope with Covid-19-related business loss and present suggestions given by them to benefit the tourism industry.

Research limitations/implications
This study offers insightful practical and theoretical implications for tourism companies, marketing practitioners and policymakers.

Originality/value
The study builds on social practice theory, and the findings (prominent themes) are uniquely mapped with the elements of social practice theory.