bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging-related iron deposit prevents the benefits of HRT from late postmenopausal atherosclerosis
Authors: Xu Tianze , Cai Jing , Wang Lei , Xu Li , Zhao Hongting , Wang Fudi , Meyron-Holtz Esther , Missirlis Fanis , Qiao Tong , Li Kuanyu 
Published: June 2022

AbstractPostmenopausal atherosclerosis has been attributed to estrogen deficiency. The beneficial effect of hormone replacement therapy (HRT), however, is lost in late postmenopausal women with atherogenesis. We asked whether aging-related iron accumulation affects estrogen receptor α (ERα) expression explaining HRT inefficacy. A negative correlation between aging-related systemic iron deposition and ERα expression in postmenopausal AS patients was established. In an ovariectomized ApoE-/- mouse model, estradiol treatment had contrasting effects on ERα expression in early versus late postmenopausal mice. ERα expression was inhibited by iron treatment in cell culture and iron-overloaded mice. Combined treatment with estradiol and iron further decreased ERα expression, mediated by iron-regulated E3 ligase Mdm2. In line with these observations, cellular cholesterol efflux was reduced and endothelial homeostasis was disrupted and, consequently, atherosclerosis was aggravated. Accordingly, systemic iron chelation attenuated estradiol-triggered progressive atherosclerosis in late postmenopausal mice. Thus, iron and estradiol together downregulate ERα through Mdm2-mediated proteolysis, explaining failures of HRT in late postmenopausal subjects with aging-related iron accumulation. HRT is recommended immediately after menopause along with appropriate iron chelation to protect from atherosclerosis.
Cerebral Organoids In Primary Progressive Multiple Sclerosis Reveal Stem Cell Disruption And Failure To Produce Oligodendrocytes
Authors: Daviaud Nicolas , Chen Eric , Edwards Tara , Sadiq Saud A 
Published: June 2022

ABSTRACTMultiple sclerosis (MS) is an auto-immune inflammatory disorder affecting the central nervous system. The cause of the disease is unknown but both genetic and environmental factors are implicated in the pathogenesis. We derived cerebral organoids from induced pluripotent stem cells (iPSC) of healthy control subjects as well as from primary progressive MS (PPMS), secondary progressive MS (SPMS) and relapsing remitting MS (RRMS) patients to better understand the pathologic basis of the varied clinical phenotypic expressions of MS. In MS organoids, most notably in PPMS, we observed a decrease of proliferation marker Ki67 and a reduction of the SOX2+ stem cell pool associated with an increased expression of neuronal markers CTIP2 and TBR1. This dysregulation of the stem cell pool is associated with a decreased expression of the cell cycle inhibitor p21. Our findings show that the genetic background of a patient can directly alter stem cell function. This study also provides new insights on the innate cellular dysregulation in MS and identifies p21 pathway as a new potential target for therapeutic strategies in MS.Summary StatementUsing cerebral organoids derived from patients with multiple sclerosis we detected that p21 decrease may induce a disruption of the stem cell cycle leading to a defect of oligodendrocyte differentiation
Regulation of urea cycle by reversible high stoichiometry lysine succinylation
Authors: Zhang Ran , Xie Xueshu , Carrico Chris , Meyer Jesse G. , Wei Lei , Bons Joanna , Rose Jacob , Riley Rebeccah , Kwok Ryan , Kumaar Prasanna A. , He Wenjuan , Nishida Yuya , Liu Xiaojing , Locasale Jason W. , Schilling Birgit , Verdin Eric 
Published: June 2022

AbstractThe post-translational modification, lysine succinylation is implicated in the regulation of various metabolic pathways. However, its biological relevance remains uncertain due to methodological difficulties in determining high-impact succinylation sites. In the present study, using stable isotope labeling and data-independent acquisition mass spectrometry, we quantified lysine succinylation stoichiometries in mouse livers. Despite the low overall stoichiometry of lysine succinylation, several high stoichiometry sites were identified, especially upon deletion of the desuccinylase SIRT5. In particular, multiple high stoichiometry lysine sites identified in argininosuccinate synthase (ASS1), a key enzyme in urea cycle, are regulated by SIRT5. Mutation of the high stoichiometry lysine in ASS1 to succinyl-mimetic glutamic acid significantly decreased its enzymatic activity. Metabolomics profiling confirms that SIRT5 deficiency decreases urea cycle activity in liver. Importantly, SIRT5 deficiency compromises ammonia tolerance and reduces locomotor and exploratory activity in male mice upon high-ammonium diet feeding. Therefore, lysine succinylation is functionally important in ammonia metabolism.
Experimental support for human papillomavirus genome amplification early after infectious delivery
Authors: Zwolinska Katarzyna , Bienkowska-Haba Malgorzata , Scott Rona S. , Sapp Martin 
Published: June 2022

ABSTRACTEven though replication and transcription of human papillomavirus type 16 (HPV16) has been intensively studied, little is known about immediate early events of the viral life cycle due to the lack of an efficient infection model allowing genetic dissection of viral factors. We employed the recently developed infection model (Bienkowska-Haba et al. PLOS Pathogen 2018) to investigate genome amplification and transcription immediately after infectious delivery of viral genome to nuclei of primary keratinocytes. Using EdU pulse labeling and highly sensitive fluorescencein situhybridization, we observed that the HPV16 genome is replicated and amplified in an E1 and E2 dependent manner. Knockout of E1 resulted in failure of the viral genome to replicate and amplify. In contrast, knockout of the E8^E2 repressor led to increased viral genome copy number confirming previous reports. Genome copy control by E8^E2 was confirmed for differentiation-induced genome amplification. Lack of functional E1 had no effect on transcription from the early promoter, suggesting that viral genome replication is not required for p97 promoter activity. However, infection with an HPV16 mutant virus defective for E2 transcriptional function revealed a requirement of E2 for efficient transcription from the early promoter. In absence of the E8^E2 protein, early transcript levels are unaltered and even decreased when normalized to genome copy number. Surprisingly, lack of functional E8^E2 repressor did not affect E8^E2 transcript levels when normalized to genome copy number. These data suggest that the main function of E8^E2 in the viral life cycle is to control genome copy number.IMPORTANCEIt is being assumed that HPV utilizes three different modes of replication during its lifecycle: initial amplification during the establishment phase, genome maintenance and differentiation-induced amplification. However, HPV16 initial amplification was never formally proven due to a lack of an infection model. Using our recently established infection model (Bienkowska-Haba et al. PLOS Pathogen 2018), we demonstrate herein that viral genome is indeed amplified in an E1 and E2 dependent manner. Furthermore, we find that the main function of the viral repressor E8^E2 is to control viral genome copy number. We did not find evidence that it regulates its own promoter in a negative feedback loop. Our data also suggest that the E2 transactivator function is required for stimulation of early promoter activity, which has been debated in the literature. Overall, this report confirms the usefulness of the infection model for studying early events of the HPV lifecycle using mutational approaches.
Human Papillomavirus Genome Copy Number Is Maintained by S Phase Amplification, Leakage to the Cytosol during Mitosis and Lysosomal Degradation in G1 Phase
Authors: Bienkowska-Haba Malgorzata , Zwolinska Katarzyna , Keiffer Timothy , Sapp Martin 
Published: June 2022

ABSTRACTThe current model for human papillomavirus (HPV) replication is comprised of three modes of replication. Following infectious delivery, the viral genome is amplified during the establishment phase to reach up to some hundred copies per cell. HPV genome copy number remains constant during the maintenance stage. Differentiation of infected cells induces HPV genome amplification. Using highly sensitive in situ hybridization (DNAscope) and freshly HPV16-infected as well as established HPV16-positive cell lines, we observed that viral genome is amplified in each S phase of undifferentiated keratinocytes cultured as monolayers. Nuclear viral genome copy number is reset to pre-S phase levels during mitosis. The majority of viral genome fails to tether to host chromosomes and is lost to the cytosol. Cytosolic viral genome gradually decreases during cell cycle progression. Loss of cytosolic genome is blocked in presence of NH4Cl or other drugs interfering with lysosomal acidification, suggesting the involvement of autophagy in viral genome degradation. These observations were also made with HPV31 cell lines obtained from patient samples. Cytosolic viral genome was not detected in UMSCC47 cells carrying integrated HPV16 DNA. Analyses of organotypic raft cultures derived from keratinocytes harboring episomal HPV16 revealed the presence of cytosolic viral genome as well. We conclude that HPV maintains viral genome copy number by balancing viral genome amplification during S phase with loss of viral genome that is lost to the cytosol during mitosis. It seems plausible that restrictions to viral genome tethering to mitotic chromosomes resets genome copy number in each cell cycle.IMPORTANCEHPV genome maintenance is currently being thought to be achieved by regulating expression and activity of viral replication factors E1 and E2. In addition, the E8^E2 repressor has been shown to be important for restricting genome copy number by competing with E1 and E2 for binding to the viral origin of replication and by recruitment of repressor complexes. Herein, we demonstrate that HPV viral genome is amplified in each S phase. Nuclear genome copy number is reset during mitosis by a failure of the majority of genomes to tether to mitotic chromosomes. Rather, they accumulate in the cytoplasm of freshly divided cells. Cytosolic viral DNA is quickly degraded in G1 in a lysosome dependent manner contributing to the genome copy reset. Our data imply that the mode of replication during establishment and maintenance is the same and further suggest that restrictions to genome tethering significantly contributes to viral genome maintenance.
Assessing the role of information and communication technology in reducing the gap between rich and poor: the case of South Asia
Authors: Ahmad Seemab , Khan Dilawar , Haq Ihtisham ul 
Published: June 2022

PurposeThe widening income gap between rich and poor has gained worldwide recognition in recent decades. This income gap between rich and poor is defined as the extent of income unevenly distributed in a host country. This study provides an empirical view of the association between information and communication technology and the widening of the income gap.Design/methodology/approachThe study used panel data from 2005 to 2019. To detect unit root issues, Levin and Lin (LL) and Im, Pesaran and Shin (IPS) tests were first employed. The pooled mean group and mean group estimators were employed to investigate the short and long -term impact of information and communication technology and other control factors on reducing the gap between rich and poor in South Asia.FindingsThe results showed that the Pooled mean group's findings are more efficient and consistent as compared to mean group estimators. The results of the paper showed that the greater penetration of information and communication technologies in the economy negatively and significantly affects income inequality. Moreover, the information and communication technology, foreign remittances and foreign direct investment (FDI) significantly reduce the gap between rich and poor in the long run.Practical implicationsAt last, the findings of the study serve as an excellent roadmap for policymakers seeking to address the issue of growing income inequality in the South Asian regions and worldwide.Originality/valueBased on the findings of this study, South Asia can reduce the gap between rich and poor by investing more in the information and communication technology sector.Peer reviewThe peer review history for this article is available at:https://publons.com/publon/10.1108/IJSE-10-2021-0638
Audit fees under the COVID-19 pandemic: evidence from Oman
Authors: Al-Qadasi Adel , Baatwah Saeed Rabea , Omer Waddah Kamal 
Published: June 2022

PurposeThe worldwide spread of the coronavirus disease 2019 (COVID-19) has significant effects on financial markets and companies, causing an unprecedented level of uncertainty in reporting and auditing companies' financial statements. This study explores whether and how COVID-19 affects audit fees.Design/methodology/approachUsing a sample of 268 firm-year observations from the Omani capital market between 2017 and 2020, the ordinary least squares (OLS) regression with a robust standard error is applied to answer the research question of this study.FindingsThe authors find that the pandemic has a significant and positive association with audit fees and abnormal audit fees. This finding suggests that the threat of risk, complexity and legal liability circumstances resulting from the pandemic can be compensated by charging higher audit fees. In addition, the authors provide evidence that Big4 audit firms are those most responding to COVID-19 by charging higher audit fees. Finally, the authors conclude that large companies are less sensitive to the pandemic.Practical implicationsUsers of financial reports and audit firms should anticipate changes in the audit efforts resulting in increased audit fees during COVID-19. Thus, this paper may guide practitioners and businesses in determining the audit fees and associated costs of any potential pandemic.Originality/valueThe study results are among the earliest empirical insights into the effect of COVID-19 on audit fees in Oman.
Longitudinal study of perceived environmental uncertainty. An application of Rasch methodology to SMES
Authors: García-Pérez Ana María , Yanes-Estévez Vanessa 
Published: June 2022

PurposeThis work develops a longitudinal analysis of perceived environmental uncertainty applying the Rasch methodology (1960). The environmental uncertainty is defined as an individual's perceived inability to predict the environment accurately (Milliken, 1987). The study focuses on analysing the state uncertainty from the perspective of the information and under the cognitive approach to the business reality.Design/methodology/approachRasch measurement theory (1960) is applied, specifically the differential item functioning analysis based on the responses to a survey of SMEs.FindingsThe main sources of uncertainty for all the SMEs in the sample are two sectors in their general environment: economic and political-legal ones. These segments are the only ones in the environment that generate uncertainty that in 2016 is significantly different from that in 2019, being lower in the latter year.Originality/valueThis is a pioneering analysis of uncertainty both for its longitudinal nature and the methodology applied.
EggLib 3: A python package for population genetics and genomics
Authors: Siol Mathieu , Coudoux Thomas , Ravel Sébastien , De Mita Stéphane 
Published: June 2022

AbstractRapid and repeatable polymorphism analyses have become a necessity with the current amount of genomic data that can be collected in many organisms. Traditionally, such analyses are conducted using a variety of tools in combination, often requiring numerous format translation and manipulation. Here, we present a massively updated version of our previous software package egglib, intended to alleviate such costly and error‐prone tinkering with the data. egglib has been streamlined into a python package and thoroughly updated and optimized to accommodate modern‐day sized dataset. We show the main characteristics of the package making it a tool of choice to perform population genetics analyses. Once the data are imported (whatever their encoding), they can be filtered, edited, analysed and compared to coalescent simulations very easily and efficiently. Furthermore, the list of diversity and polymorphism statistics that can now be calculated has been greatly expanded. The software and its full documentation are available at https://egglib.org/.
The Effect of Reporting Opacity on Trading Opacity: New Evidence from American Depositary Receipt Trades in Dark Pools*
Authors: Boulton Thomas J. , Braga‐Alves Marcus V. , Chakrabarty Bidisha 
Published: June 2022

ABSTRACTTrading volume is increasingly shifting to dark venues, and the causes of this move are not well understood. We examine whether a firm's reporting opacity affects its dark pool trading and provide robust evidence that (partly) explains this volume migration. Exploiting the exogenous variation in home‐country reporting opacity in a sample of American Depositary Receipts (ADRs) and using multiple metrics for reporting opacity, we find that greater opacity associates with increased dark pool trading. This relation holds after controlling for firms' information environments, country‐specific governance issues, observable differences between ADRs and other securities that trade in dark pools (matched sample analysis), volume migration to dark pools during earnings announcements, informed trading in lit versus dark venues, ADR levels, IFRS reporting requirements, and the possible endogenous determination of home‐country reporting opacity and dark pool volume. The positive relation is stronger for ADRs held by (quasi‐indexing) institutions with low turnover and diversified holdings and weaker for ADRs favored by (transient) institutions that trade frequently and (dedicated) institutions that hold concentrated portfolios. Bid‐ask spreads are greater for higher opacity ADRs that trade in dark pools, indicating that reporting opacity is associated with the negative effect of dark pool trading on market quality. Our findings help inform the current debate on off‐exchange trading by showing how reporting regimes affect the trading venue choice.
TheWeight: A simple and flexible algorithm for simulating non‐ideal, age‐structured populations
Authors: Waples Robin S. 
Published: June 2022

Abstract

The Wright–Fisher model, which directs how matings occur and how genes are transmitted across generations, has long been a lynchpin of evolutionary biology. This model is elegantly simple, analytically tractable and easy to implement, but it has one serious limitation: essentially no real species satisfies its many assumptions. With growing awareness of the importance of jointly considering both ecology and evolution in eco‐evolutionary models, this limitation has become more apparent, causing many researchers to search for more realistic simulation models.

A recently described variation retains most of the Wright–Fisher simplicity but provides greater flexibility to accommodate departures from model assumptions. This generalized Wright–Fisher model relaxes the assumption that all individuals have identical expected reproductive success by introducing a vector of parental weights w that specifies relative probabilities different individuals have of producing offspring. With parental weights specified this way, expectations of key demographic parameters are simple functions of w. This allows researchers to quantitatively predict the consequences of non‐Wright–Fisher features incorporated into their models.

An important limitation of the Wright–Fisher model is that it assumes discrete generations, whereas most real species are age structured. Here I show how an algorithm (TheWeight) that implements the generalized Wright–Fisher model can be used to model evolution in age‐structured populations with overlapping generations. Worked examples illustrate simulation of seasonal and lifetime reproductive success and show how the user can pick vectors of weights expected to produce a desired level of reproductive skew or a desired Ne/N ratio. Alternatively, weights can be associated with heritable traits to provide a simple, quantitative way to model natural selection. Using TheWeight, it is easy to generate positive or negative correlations of individual reproductive success over time, thus allowing explicit modelling of common biological processes like skip breeding and persistent individual differences.

Code is provided to implement basic features of TheWeight and applications described here, including one scenario implemented in SLiM. However, required coding changes to the Wright–Fisher model are modest, so the real value of the new algorithm is to encourage users to adopt its features into their own or others' models.
Former auditors on the audit committee and earnings management: Evidence from African banks
Authors: Mnif Yosra , Slimi Imen 
Published: June 2022

AbstractThis paper investigates whether former auditors on the audit committee constrain earnings management through loan loss provisions. Based on an analysis of the annual reports of 82 African listed banks over the period 2011–2016, findings show that the presence of former auditors on an audit committee is associated with lower earnings management. This result suggests that audit committee members with auditing expertise and background contribute to effective monitoring of management’s accounting practices. Furthermore, results reveal that the reducing effect on earnings management of former auditors is strongest for directors who are unaffiliated with the bank’s current external auditor.
Fire severity and the post‐fire soil environment affect seedling regeneration success of the threatened Persoonia hirsuta (Proteaceae)
Authors: Andres Samantha E. , Powell Jeff R. , Rymer Paul D. , Emery Nathan J. 
Published: June 2022

AbstractClimate change and land management decisions have considerably altered fire regimes globally resulting in increased risks of extreme fire seasons. Fire intensity is one characteristic of fire regime which is projected to increase. However, the magnitude and impact of intense fires on plant habitat and life history characteristics (such as the soil environment or seedling recruitment) remain unclear for many species. The widespread 2019–2020 Black Summer fires across Eastern Australia provided the opportunity to examine the impact of these fires on the short‐term regeneration of the Endangered Persoonia hirsuta (Proteaceae), an obligate seeding (reliant on regeneration from seed following fire) shrub presently threatened by population decline and dieback (plant death from branch and root tips backwards) of an unknown cause. In this study, we used a combination of metrics to estimate fire severity in the field at 22 plots across three fire‐affected populations which we used as a proxy to understand the relative impacts of fire intensity on P. hirsuta regeneration post‐fire. We also recorded the recruitment, growth, dieback and mortality of P. hirsuta seedlings at these plots over 21 months following the fires and examined whether the post‐fire soil environment (carbon, nitrogen and phosphorus) was related to fire severity and seedling responses. Seedling recruitment and growth were variable across sites and showed no relationship to fire severity. However, seedling dieback and mortality were significantly higher among plots exposed to high severity fires. Additionally, characteristics of the post‐fire soil environment varied by fire severity and explained variation in seedling recruitment, growth and dieback. Our work provides important evidence that already vulnerable populations of P. hirsuta may be further threatened by increasing fire severity, highlighting the importance of understanding the effects of fire on habitat and life history characteristics for threatened plants.