bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin landscape dynamics in development of the plant parasitic nematode Meloidogyne incognita
Authors: Hassanaly-Goulamhoussen Rahim , De Carvalho Augusto Ronaldo , Marteu-Garello Nathalie , Péré Arthur , Favery Bruno , Da Rocha Martine , Danchin Etienne G.J. , Abad Pierre , Grunau Christoph , Perfus-Barbeoch Laetitia 
Published: May 2021

AbstractIn model organisms, epigenome dynamics underlies a plethora of biological processes. The role of epigenetic modifications in development and parasitism in nematode pests remains unknown. The root-knot nematode Meloidogyne incognita adapts rapidly to unfavorable conditions, despite its asexual reproduction. However, the mechanisms underlying this remarkable plasticity and their potential impact on gene expression remain unknown. This study provides the first insight into contribution of epigenetic mechanisms to this plasticity, by studying histone modifications in M. incognita. The distribution of five histone modifications revealed the existence of strong epigenetic signatures, similar to those found in the model nematode Caenorhabditis elegans. We investigated their impact on chromatin structure and their distribution relative to transposable elements (TE) loci. We assessed the influence of the chromatin landscape on gene expression at two developmental stages: eggs, and pre-parasitic juveniles. H3K4me3 histone modification was strongly correlated with high levels of expression for protein-coding genes implicated in stage-specific processes during M. incognita development. We provided new insights in the dynamic regulation of parasitism genes kept under histone modifications silencing. In this pioneering study, we establish a comprehensive framework for the importance of epigenetic mechanisms in the regulation of the genome expression and its stability in plant-parasitic nematodes.Author summaryThe nematode Meloidogyne incognita is one of the most destructive plant parasites worldwide. Its ability to infect a wide range of hosts and its high adaptability contribute to its parasitic success. We investigated the role of epigenetic mechanisms — specifically post-translational histone modifications — in the parasitic life cycle. We showed these modifications are linked to gene expression regulation and likely contribute to nematode development and pathogenicity.
CdrS is a global transcriptional regulator influencing cell division inHaloferax volcanii
Authors: Liao Yan , Vogel Verena , Hauber Sabine , Bartel Jürgen , Alkhnbashi Omer S. , Maaß Sandra , Schwarz Thandi S. , Backofen Rolf , Becher Dörte , Duggin Iain G. , Marchfelder Anita 
Published: May 2021

AbstractTranscriptional regulators that integrate cellular and environmental signals to control cell division are well known in bacteria and eukaryotes, but their existence is poorly understood in archaea. We identified a conserved gene (cdrS)that encodes a small protein and is highly transcribed in the model archaeonHaloferax volcanii. ThecdrSgene could not be deleted, but CRISPRi-mediated repression of thecdrSgene caused slow growth, cell division defects, and changed the expression of multiple genes and their products associated with cell division, protein degradation and metabolism. Consistent with this complex regulatory network, overexpression ofcdrSinhibited cell division, whereas overexpression of the operon encoding both CdrS and a tubulin-like cell division protein (FtsZ2) stimulated division. ChIP-Seq identified 18 DNA-binding sites of the CdrS protein including one upstream of the promoter for diadenylate cyclase, which is an essential gene involved in c-di-AMP signalling implicated in the regulation of cell division. These findings suggest that CdrS is a transcription factor that plays a central role in a regulatory network coordinating metabolism and cell division.ImportanceCell division is a central mechanism of life, and is essential for growth and development. Bacteria and Eukarya have different mechanisms for cell division, which have been studied in detail. In contrast, cell division in Archaea is still understudied, and its regulation is poorly understood. Interestingly, different cell division machineries appear in the Archaea, with the Euryarchaeota using a cell division apparatus based on the tubulin-like cytoskeletal protein FtsZ, as in bacteria. Here we identify the small protein CdrS as essential for survival and a central regulator of cell division in the EuryarchaeonHaloferax volcanii. CdrS also appears to coordinate other cellular pathways including synthesis of signalling molecules and protein degradation. Our results show that CdrS plays a sophisticated role in cell division, including regulation of numerous associated genes. These findings are expected to initiate investigations into conditional regulation of division in archaea.
Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir
Authors: Soh Y.Q. Shirleen , Malone Keara D. , Eguia Rachel T. , Bloom Jesse D. 
Published: May 2021

AbstractAntivirals are used not only in current treatment of influenza, but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide clinical deployment of the antiviral, and additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.
Non-coding RNAs Associated with Prader-Willi Syndrome Regulate Transcription of Neurodevelopmental Genes in Human Induced Pluripotent Stem Cells
Authors: Sledziowska Monika , Jones Matt , Maghrabi Ruba Al , Hebenstreit Daniel , Garcia Paloma , Grzechnik Pawel 
Published: May 2021

ABSTRACTMutations and aberrant gene expression during cellular differentiation lead to neurodevelopmental disorders such as Prader-Willi syndrome (PWS) which results from the deletion of an imprinted locus on chromosome 15. We analysed chromatin-associated RNA in human induced pluripotent cells (iPSCs) upon depletion of hybrid small nucleolar long non-coding RNAs (sno-lncRNAs) and 5’ snoRNA capped and polyadenylated long non-coding RNAs (SPA-lncRNAs) transcribed from the locus deleted in PWS. We found that rapid ablation of these lncRNAs affects transcription of specific gene classes. Downregulated genes contribute to neurodevelopment and neuronal maintenance while genes that are upregulated are predominantly involved in the negative regulation of cellular metabolism and apoptotic processes. Our data revealed the importance of SPA-lncRNAs and sno-lncRNAs in controlling gene expression in iPSCs and provided a platform for synthetic experimental approaches in PWS studies. We conclude that ncRNAs transcribed from the PWS locus are critical regulators of a transcriptional signature important for neuronal differentiation and development.
Molecular basis and functional consequences of the interaction between the Base Excision Repair DNA glycosylase NEIL1 and RPA
Authors: Le Meur Rémy A. , Pecen Turner J. , Le Meur Kateryna V. , Nagel Zachary D. , Chazin Walter J. 
Published: May 2021

AbstractNEIL1 is a DNA glycosylase that recognizes and initiates base excision repair of oxidized bases. The ubiquitous ssDNA binding scaffolding protein replication protein A (RPA) modulates NEIL1 activity in a manner that depends on DNA structure. Interaction between NEIL1 and RPA has been reported, but the molecular basis of this interaction has yet to be investigated. Using a combination of NMR spectroscopy and isothermal titration calorimetry (ITC), we show that NEIL1 interacts with RPA through two contact points. An interaction with the RPA32C protein recruitment domain was mapped to a motif in the common interaction domain (CID) of NEIL1 and a dissociation constant (Kd) of 200 nM was measured. A substantially weaker secondary interaction with the tandem RPA70AB ssDNA binding domains was also mapped to the CID. Together these two contact points reveal NEIL1 has a high overall affinity (Kd ∼ 20 nM) for RPA. A homology model of the complex of RPA32C with the NEIL1 RPA binding motif in the CID was generated and used to design a set of mutations in NEIL1 to disrupt the interaction, which was confirmed by ITC. The mutant NEIL1 remains catalytically active against ionizing radiation-induced DNA lesions in duplex DNA in vitro. Testing the functional effect of disrupting the NEIL1-RPA interaction in vivo using a Fluorescence Multiplex-Host Cell Reactivation (FM-HCR) reporter assay revealed that RPA interaction is not required for NEIL1 activity against oxidative damage in duplex DNA, and furthermore revealed an unexpected role for NEIL1 in nucleotide excision repair. These findings are discussed in the context of the role of NEIL1 in replication-associated repair.
Brainstem cholinergic modulation of the thalamocortical activity in urethane anesthetized mice
Authors: Hay Y Audrey 
Published: May 2021

ABSTRACTIn mammals, sleep consists in the recurrence of two main stages the rapid eye movement (REM) sleep and the slow wave sleep (SWS). The full expression of sleep rhythms requires an intact thalamocortical loop, and its modulation by neuromodulators such as acetylcholine. A high tone of acetylcholine is observed during REM sleep while a low tone of acetylcholine modulates the cortical slow waves during SWS. Brainstem Cholinergic neurons activity correlates with cortical sleep stages but these neurons do not project directly to the cortex. Instead, they could contribute to cortically-recorded sleep stage modulation via a thalamic relay, in particular via the midline thalamic nuclei. Focusing on the brainstem LDTg cholinergic neurons, I investigated how midline thalamic single unit activity and cortical sleep-like stages are modulated during optogenetic-induced activation or silencing of LDTg cholinergic neurons in urethane anesthetized mice. Thalamic neurons were more active during REM-like than SWS-like stages. Bursting activity predominated during SWS-like while tonic firing was prominent during REM-like stage. Optogenetic silencing of the brainstem LDTg cholinergic neurons abolished REM-like stages and reduced tonic spiking of thalamic neurons. Moreover, during SWS-like, silent Down states were prolonged and thalamic tonic spiking during Up states was reduced. Stimulation of the brainstem LDTg cholinergic neurons had a mild effect on thalamic activity even though tonic discharge was increased. Surprisingly, optogenetic stimulation abolished as well REM-like stages maybe through compensatory mechanisms.
FDI inflows and bank deposits: evidence from 18 MENA economies
Authors: Saif-Alyousfi Abdulazeez Y.H. 
Published: May 2021

Purpose
This paper aims to examine and compare the impact of foreign direct investment (FDI) inflows on bank deposits in aggregate as well as at the level of conventional and Islamic banks in Middle East and North Africa (MENA) countries. The study also tests hypotheses of direct and indirect impacts of FDI flow and FDI stock on bank deposits.

Design/methodology/approach
Static and dynamic panel generalized methods of moments (GMM) estimation techniques are applied to analyze a large data set of 491 commercial banks (422 conventional banks and 69 Islamic banks) across 18 MENA countries between 1993 and 2017 (12,275 year observations).

Findings
Empirical results indicate that inflowing FDI flow and FDI stock have a significant negative direct impact on deposits of MENA banks. The results lend support for the direct channel hypothesis for the effect of FDI on bank deposits and find no evidence in support of the indirect channel hypothesis. FDI inflows affect bank deposits directly via increased FDI-related excessive competition in the banking market. Deposits from conventional banks appear to be more affected than those from Islamic banks. The variation may due to the fact that Islamic banks have fewer multinational corporations (MNC) customers than conventional banks and therefore are less sensitive to fluctuations in FDI.

Practical implications
From this analysis, this study concludes that foreign investments have a higher productivity than local investments in MENA region. Attracting more FDI is aimed at increasing overall national productivity through competition. However, governments would be wise to enact such a policy to maximize benefits and minimize potential harm to local industry. Furthermore, FDI policy should encourage small to medium-size banks and firms (SMEs)’ participation and linkage with multinational banks and MNCs, while upgrading research and development institutions and innovation activities to help SMEs to benefit from potential spillovers from foreign presence in the industry. In addition, the linkage and connection between SMEs and foreign firms should be strengthened and promoted by government policy.

Originality/value
This study is the first of its kind to examine the effect of FDI inflows on bank deposits. It also provides an in-depth quantitative analysis of the impact of FDI flow and FDI stock, separately, on bank deposits for both conventional and Islamic banks. It distinguishes between direct and indirect channels through which FDI inflows may affect bank deposits. The study analyzes 25 years of panel data for 491 banks (12,275 year observations) and uses both static and dynamic panel GMM estimation techniques to analyze the data.
An investigation of factors influencing intercultural communication competence of the international students from a higher education institute in Malaysia
Authors: Nadeem Muhammad Umar , Mohammed Rosli , Dalib Syarizan , Mumtaz Samavia 
Published: May 2021

PurposeThe purpose of this study is to highlight the importance of intercultural communication competence (ICC) of international students living in Malaysia. This study considered the culture-general factors of integrated model of ICC (IMICC) established from the West with an addition of empathy and further addressed these influencers on the international students from a Malaysian university. It is proposed that empathy, sensation seeking, ethnocentrism, attitude and motivation have a direct influence on ICC.Design/methodology/approachA quantitative research methodology was considered to address the relationship between the variables of this study. Data were collected through a survey by visiting different parts of the university campus. A total of 388 international students took part in the study voluntarily. Data were analysed using statistical package for social sciences (SPSS) and structural equation modeling-analysis of a moment structures (SEM-AMOS).FindingsThe findings revealed that empathy, sensation seeking and attitude are the antecedents of ICC. However, ethnocentrism and motivation do not influence ICC significantly.Originality/valueThrough the findings of this study, a series of training sessions can be conducted by Malaysia (host country training) and sender countries (home country training) to educate international students regarding ICC. Furthermore, ministry of higher education (MoHE) Malaysia and higher education institutes (HEIs) can improve their infrastructure and services in terms of hosting and accommodating more international students by considering the findings of this study. These approaches could help international students to adjust in a new cultural setting of Malaysia.
Cross-border banking and foreign branch regulation in Europe
Authors: Gibilaro Lucia , Mattarocci Gianluca 
Published: May 2021

PurposeThis paper aims to examine the relevance of cross-border activity in the European banking sector, evaluating the role of differences in regulation to explain the level of interest in entering foreign markets.Design/methodology/approachThe sample considers all banks in the European Union (EU 28) existing at year-end 2017, and information about the ultimate owners’ nationality to classify local and foreign banks is collected. The analysis provides a mapping of regulatory restrictions for foreign banks and evaluates how they impact the role of foreign players in the deposit and lending markets.FindingsResults show that the lower are the capital adequacy requirements, the higher are the amounts of loans and deposits offered by non-European Economic Area banks and, additionally, the higher the probability of having a foreign bank operating in the country.Originality/valueThis paper provides new evidence on regulatory arbitrage opportunities in the EU and outlines differences among EU countries not previously studied.
Polypharmacy as maintenance treatment in bipolar illness: A systematic review
Authors: Amerio Andrea , Russo Daniel , Miletto Norberto , Aguglia Andrea , Costanza Alessandra , Benatti Beatrice , Odone Anna , Barroilhet Sergio A. , Brakoulias Vlasios , Dell’Osso Bernardo , Serafini Gianluca , Amore Mario , Ghaemi S. Nassir 
Published: May 2021

ABSTRACTObjectivesPolypharmacy is common in maintenance treatment of bipolar illness, but proof of greater efficacy compared to monotherapy is assumed rather than well known. We systematically reviewed the evidence from the literature to provide recommendations for clinical management and future research.MethodA systematic review was conducted on the use of polypharmacy in bipolar prophylaxis. Relevant papers published in English through 31 December 2019 were identified searching the electronic databases MEDLINE, Embase, PsycINFO, and the Cochrane Library.ResultsTwelve studies matched inclusion criteria, including 10 randomized controlled trials (RCTs). The best drug combination in prevention is represented by lithium + valproic acid which showed a significant effect on time to mood relapses (HR = 0.57) compared to valproic acid monotherapy, especially for manic episodes (HR = 0.51). The effect was significant in terms of time to new drug treatment (HR = 0.51) and time to hospitalization (HR = 0.57). A significant reduction in the frequency of mood relapses was also reported for lithium + valproic acid vs. lithium monotherapy (RR=0.12); however, the trial had a small sample size. Lamotrigine + valproic acid reported significant efficacy in prevention of depressive episodes compared to lamotrigine alone.ConclusionsThe literature to support a generally greater efficacy with polypharmacy in bipolar illness is scant and heterogeneous. Within that limited evidence base, the best drug combination in bipolar prevention is represented by lithium + valproic acid for manic, but not depressive episodes. Clinical practice should focus more on adequate monotherapy before considering polypharmacy.
Aquaporin 4 differentially modulates osmotic effects on vasopressin neurons in rat supraoptic nucleus
Authors: Wang Xiaoran , Li Tong , Liu Yang , Jia Shuwei , Liu Xiaoyu , Jiang Yunhao , Wang Ping , Parpura Vladimir , Wang Yu‐Feng 
Published: May 2021

AbstractAimGlial fibrillary acidic protein (GFAP) molecularly associates with aquaporin 4 (AQP4) in astrocytic plasticity. Here, we further examined how AQP4 modulates osmotic effects on vasopressin (VP) neurons in rat supraoptic nucleus (SON) through interactions with GFAP in astrocytes.MethodsBrain slices from adult male rats were kept under osmotic stimulation. Western blot, co‐immunoprecipitation, immunohistochemistry and patch‐clamp recordings were used for analysis of expressions and interactions between GFAP and AQP4, astrocyte‐specific proteins in the SON, as well as their influence on VP neuronal activity. Data were analysed using SPSS software.ResultsHyposmotic challenge (HOC) of acute SON slices caused an early (within 5 minutes) and transient increase in the colocalization of AQP4 with GFAP filaments. This effect was prominent at astrocytic processes surrounding VP neuron somata and was accompanied by inhibition of VP neuronal activity. Similar HOC effect was seen in the SON isolated from rats subjected to in vivo HOC, wherein a transiently increased molecular association between GFAP and AQP4 was detected using co‐immunoprecipitation. The late stage rebound excitation (10 minutes) of VP neurons in brain slices subjected to HOC and the associated astrocytic GFAP’s ‘return to normal’ were both hampered by 2‐(nicotinamide)‐1,3,4‐thiadiazole, a specific AQP4 channel blocker that itself did not influence VP neuronal activity. Moreover, this agent prevented hyperosmotic stress‐evoked excitation of VP neurons and associated reduction in GFAP filaments.ConclusionThese findings indicate that osmotically driven increase in VP neuronal activity requires the activation of AQP4, which determines a retraction of GFAP filaments.
Effect of CES1 genetic variation on enalapril steady‐state pharmacokinetics and pharmacodynamics in healthy subjects
Authors: Her Lucy H. , Wang Xinwen , Shi Jian , Choi Hee Jae , Jung Sun Min , Smith Logan S. , Wu Audrey H. , Bleske Barry E. , Zhu Hao‐Jie 
Published: May 2021

AimsEnalapril is a prodrug and needs to be activated by carboxylesterase 1 (CES1). A previous in vitro study demonstrated the CES1 genetic variant, G143E (rs71647871), significantly impaired enalapril activation. Two previous clinical studies examined the impact of G143E on single‐dose enalapril PK (10 mg); however, the results were inconclusive. A prospective, multi‐dose, pharmacokinetics and pharmacodynamics (PK/PD) study was conducted to determine the impact of the CES1 G143E variant on enalapril steady‐state PK and PD in healthy volunteers.MethodsStudy participants were stratified to G143E non‐carriers (n = 15) and G143E carriers (n = 6). All the carriers were G143E heterozygotes. Study subjects received enalapril 10 mg daily for seven consecutive days prior to a 72 hour PK/PD study. Plasma concentrations of enalapril and its active metabolite enalaprilat were quantified by an established liquid chromatography–tandem mass spectrometry (LC–MS/MS) method.ResultsThe CES1 G143E carriers had 30.9% lower enalaprilat Cmax (P =  0.03) compared to the non‐carriers (38.01 vs. 55.01 ng/mL). The carrier group had 27.5% lower AUC0–∞ (P =  0.02) of plasma enalaprilat compared to the non‐carriers (374.29 vs. 515.91 ng*h/mL). The carriers also had a 32.3% lower enalaprilat‐to‐enalapril AUC0–∞ ratio (P =  0.003) relative to the non‐carriers. The average maximum reduction of systolic blood pressure in the non‐carrier group was approximately 12.4% at the end of the study compared to the baseline (P =  0.001). No statistically significant blood pressure reduction was observed in the G143E carriers.ConclusionsThe CES1 loss‐of‐function G143E variant significantly impaired enalapril activation and its systolic blood pressure‐lowering effect in healthy volunteers.