bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-137 and miR-122, two outer subventricular zone-enriched non-coding RNAs, regulate basal progenitor expansion and neuronal differentiation
Authors: Tomasello Ugo , Klingler Esther , Niquille Mathieu , Mule Nandkishor , de Vevey Laura , Prados Julien , Santinha Antonio J , Platt Randall , Borrell Victor , Jabaudon Denis , Dayer Alexandre 
Published: April 2021

AbstractCortical expansion in the primate brain relies on the presence and the spatial enlargement of multiple germinal zones during development and on a prolonged developmental period. In contrast to other mammals, which have two cortical germinal zones, the ventricular zone (VZ) and subventricular zone (SVZ), gyrencephalic species display an additional germinal zone, the outer subventricular zone (OSVZ), which role is to increase the number and types of neurons generated during corticogenesis. How the OSVZ emerged during evolution is poorly understood but recent studies suggest a role for non-coding RNAs, which allow tight regulations of transcriptional programs in time and space during development (Dehay et al. 2015; Arcila et al., 2014). Here, usingin vivofunctional genetics, single-cell RNA sequencing, live imaging and electrophysiology to assess progenitor and neuronal properties in mice, we identify two ferret and human OSVZ-enriched microRNAs (miR), miR-137 and miR-122, which regulate key cellular features associated with cortical expansion. MiR-137 promotes basal progenitor self-replication and superficial layer neuron fate, while miR-122 slows down neuronal differentiation pace. Together, these findings support a cell-type specific role for miR-mediated transcriptional regulation in cortical expansion.
A meta-analysis of areas of structural variation in grey matter in individuals with Autism Spectrum Disorder (ASD) in relation to gene expression of candidate ASD genes
Authors: Panzeri Elisa , Camasio Alessia , Mancuso Lorenzo , Liloia Donato , Manuello Jordi , Ferraro Mario , Cauda Franco , Costa Tommaso 
Published: April 2021

AbstractAutism Spectrum Disorder (ASD) is a set of developmental pathologies with a strong genetic basis and high heritability. Although neuroimaging studies have indicated anatomical changes in grey matter (GM) morphometry, their associations with gene expression remain elusive. In the present study, we aim to understand how gene expression correlates with structural brain aberration in ASD and how it distributes in a functional network perspective. First, we performed an activation likelihood estimation (ALE) meta-analysis to determine GM alteration in the brain, then we selected genes from the SHANK, NRXN, NLGN family and MECP2, which have been implicated with ASD, particularly in regards to altered synaptic transmission. Gene expression maps were built. We then assessed the correlation between the gene expression maps and the GM alteration maps. We found that the default mode network regions were the most significantly correlated with gene expression of selected genes in both areas of GM decrease and increase. The dorsal attention and the cerebellar network regions are significantly correlated with ASD genes. Different networks, namely somatomotor, limbic and basal ganglia/thalamus network - were found in the increase; for each of these networks, however, only a few genes were significant. Our approach allowed to combine the well beaten path of genetic and brain imaging in a novel way, to specifically investigate the relation between gene expression and brain with structural damage, and individuate genes of interest for further investigation in specific functional networks.
Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?
Authors: Shook Lydia L , Bordt Evan A , Meinsohn Marie-Charlotte , Pepin David , De Guzman Rose M , Brigida Sara , Yockey Laura J , James Kaitlyn E , Sullivan Mackenzie W , Bebell Lisa M , Roberts Drucilla J , Kaimal Anjali J , Li Jonathan Z , Schust Danny , Gray Kathryn J , Edlow Andrea G 
Published: April 2021

AbstractBackgroundSex differences in vulnerability to and severity of SARS-CoV-2 infection have been described in non-pregnant populations. ACE2 and TMPRSS2, host molecules required for viral entry, are regulated by sex steroids and expressed in the placenta. We sought to investigate whether placentalACE2andTMPRSS2expression vary by fetal sex and in the presence of maternal SARS-CoV-2 infection.MethodsPlacental ACE2 and TMPRSS2 were quantified in 68 pregnant individuals (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. Maternal SARS-CoV-2 status was determined by nasopharyngeal RT-PCR. Placental SARS-CoV-2 viral load was quantified. RTqPCR was performed to quantify expression ofACE2andTMPRSS2relative to the reference geneYWHAZ. Western blots were performed on placental homogenates to quantify protein levels. The impact of fetal sex and SARS-CoV-2 exposure on ACE2 and TMPRSS2 expression was analyzed by 2-way ANOVA.ResultsSARS-CoV-2 virus was undetectable in all placentas. Maternal SARS-CoV-2 infection impacted TMPRSS2 placental gene and protein expression in a sexually dimorphic fashion (2-way ANOVA interaction p-value: 0.002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on placental ACE2 gene or protein expression. PlacentalTMPRSS2expression was significantly correlated withACE2expression in males (Spearman’s ρ=0.54, p=0.02) but not females (ρ=0.23, p=0.34) exposed to maternal SARS-CoV-2.ConclusionsSex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection. These findings may have implications for offspring vulnerability to placental infection and vertical transmission.These findings may have implications for offspring vulnerability to placental infection and vertical transmission.
Induction of Dopaminergic Neurons for Neuronal Subtype-Specific Modeling of Psychiatric Disease Risk
Authors: Powell Samuel K. , O’Shea Callan , Townsley Kayla , Prytkova Iya , Dobrindt Kristina , Elahi Rahat , Iskhakova Marina , Lambert Tova , Valada Aditi , Liao Will , Ho Seok-Man , Slesinger Paul A. , Huckins Laura M. , Akbarian Schahram , Brennand Kristen J. 
Published: April 2021

ABSTRACTDopaminergic neurons are critical to movement, mood, addiction, and stress. Current techniques for generating dopaminergic neurons from human induced pluripotent stem cells (hiPSCs) yield heterogenous cell populations with variable purity and inconsistent reproducibility between donors, hiPSC clones, and experiments. Here, we report the rapid (5 weeks) and efficient (~90%) induction of induced dopaminergic neurons (iDANs) through transient overexpression of lineage-promoting transcription factors combined with stringent selection across five donors. We observe maturation-dependent increase in dopamine synthesis, together with electrophysiological properties consistent with midbrain dopaminergic neuron identity, such as slow-rising after hyperpolarization potentials, an action potential duration of ~3ms, tonic sub-threshold oscillatory activity, and spontaneous burst firing at frequency of ~1.0-1.75 Hz. Transcriptome analysis reveals robust expression of genes involved in fetal midbrain dopaminergic neuron identity. Specifically expressed genes in iDANs, relative to their isogenic glutamatergic and GABAergic counterparts, were linked to the genetic risk architecture of a broad range of psychiatric traits, with iDANs showing particularly strong enrichment in loci conferring heritability for cannabis use disorder, schizophrenia, and bipolar disorder. Therefore, iDANs provide a critical tool for modeling midbrain dopaminergic neuron development and dysfunction in psychiatric disease.
Monitoring iron-sulfur cluster occupancy across theE. coliproteome using chemoproteomics
Authors: Bak Daniel W. , Weerapana Eranthie 
Published: April 2021

AbstractIron-sulfur (Fe-S) clusters are ubiquitous metallocofactors found across diverse protein families, where they perform myriad functions including redox chemistry, radical generation, and gene regulation. Monitoring Fe-S cluster occupancy in protein targets directly within native biological systems has been challenging. Commonly utilized spectroscopic methods to detect Fe-S clusters require purification of proteins prior to analysis. Global iron incorporation into the proteome can be monitored using radiolabeled iron, but limitations include the low resolution afforded by gel-based autoradiography. Here, we report the development of a mass spectrometry-based strategy to assess Fe-S cluster binding in a native proteome. This chemoproteomic strategy relies on monitoring changes in the reactivity of Fe-S cluster cysteine ligands upon disruption of Fe-S cluster incorporation. Application toE. colicells cultured under iron-depleted conditions enabled monitoring of disruptions to Fe-S cluster incorporation broadly across theE. coliFe-S proteome. Evaluation ofE. colideletion strains of three scaffold proteins within the Isc Fe-S biogenesis pathway enabled the identification of Fe-S clients that are reliant on each individual scaffold protein for proper cluster installation. Lastly, cysteine-reactivity changes characteristic of Fe-S ligands were used to identify previously unannotated Fe-S proteins, including the tRNA hydroxylase, TrhP, and a member of a family of membrane transporter ATPase subunits, DppD. In summary, the chemoproteomic strategy described herein provides a powerful tool to report on Fe-S cluster incorporation directly within a native proteome, to interrogate the role of scaffold and accessory proteins within Fe-S biogenesis pathways, and to identify previously uncharacterized Fe-S proteins.
Genome expression dynamics reveals parasitism regulatory landscape of the root-knot nematodeMeloidogyne incognitaand a promoter motif associated with effector genes
Authors: Da Rocha Martine , Bournaud Caroline , Dazenière Julie , Thorpe Peter , Pellegrin Clement , Bailly-Bechet Marc , Péré Arthur , Grynberg Priscila , Perfus-Barbeoch Laetitia , Eves-van den Akker Sebastian , Danchin Etienne GJ 
Published: April 2021

AbstractRoot-knot nematodes are the major contributor to the crop losses caused by nematodes. Root-knot nematodes secrete effectors into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effectors. The details of how root-knot nematodes regulate transcription remain sparse.Here, we report a life stage-specific transcriptome ofMeloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands: providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across theMeloidogynegenus and termed it Mel-DOG.Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode, and identify a new set of candidate effector genes that will guide future functional analyses.
Unsaturated fatty acids profiling in liveC. elegansusing real-time NMR spectroscopy
Authors: Cravero Bruno Hernández , Prez Gastón , Lombardo Verónica A. , Binolfi Andrés , de Mendoza Diego 
Published: April 2021

ABSTRACTUnsaturated fatty acids (UFAs) impact central cellular process in animals such as membrane function, development and disease. Perturbations of UFAs homeostasis contribute to the onset of metabolic, cardiovascular and neurodegenerative disorders. Nevertheless, links between lipid desaturation fluctuations and the dynamics of mono and polyunsaturated fatty acid synthesis in live animal physiology are poorly understood. To advance in the understanding of this process, we decided to studyde novoUFAs synthesis with the highest resolution possible in liveCaenorhabditis elegans. Conventional lipid analysis in this organism involves solvent extraction procedures coupled with analytical techniques such as chromatography and/or mass spectrometry. These methodologies are destructive and prevent the access of information, linkingin vivoUFA dynamics and functionality. To overcome these limitations, we used uniform13C isotope labeling and real-time 2D heteronuclear NMR spectroscopy in liveC. elegansto identify their UFA compositions and the dynamic response of these fatty acids during cold adaptation. Our methodology allowed us to monitor in real time the upregulation of UFA synthesis when ambient temperature is decreased. The analysis of UFAs synthesis in worms lacking the adiponectin receptor AdipoR2 homolog PAQR-2 during a temperature drop supports the pivotal role of this protein in low temperature adaptation and survival. Our results provide new insights about the environmental regulation of UFAs and establish methodological benchmarks for future investigations of fatty acid regulation under experimental conditions that recapitulate human diseases.
Optogenetic stimulation of BLA terminals in the BNST elicits long term synaptic plasticity and restores synaptic alterations induced by adolescentShank3downregulation
Authors: Glangetas Christelle , Contestabile Alessandro , Espinosa Pedro , Casarotto Giulia , Musardo Stefano , Bellone Camilla 
Published: April 2021

AbstractAnxiety disorders are the most prevalent co-morbidity factor associated with the core domains of Autism Spectrum Disorders (ASD). Investigations on potential common neuronal mechanisms that may explain the co-occurrence of ASD and anxiety disorders are still poorly unexplored. One of the key questions which remained unsolved is the role of Shank3 protein in anxiety behaviors. Here we used shRNA strategy to model Shank3 insufficiency in the bed nucleus of the stria terminalis (BNST). We found thatShank3downregulation in the BNST induced anxiogenic effects. Associated with these behavioural defects, we showed alteration of glutamatergic synaptic functions in the BNST induced by Shank3 insufficiency during adolescence. In addition, we pointed that adolescence represents a crucial time window to interfere with BNST maturation, a key hub for anxiety control. Together, these results unravelled the crucial role of Shank3 expression in the BNST during adolescence. Our study provided a new insight in the neuronal mechanisms underlying anxiety disorders. We proposed to screen a novel molecular target essential for BNST integrity during adolescence. This result may further help for the diagnosis and the development of therapeutic strategy for anxiety disorders and anxiety disorders implicated in some forms of ASD.
Benchmarking scRNA-seq imputation tools with respect to network inference highlights deficits in performance at high levels of sparsity
Authors: Steinheuer Lisa Maria , Canzler Sebastian , Hackermüller Jörg 
Published: April 2021

AbstractGene correlation network inference from single-cell transcriptomics data potentially allows to gain unprecendented insights into cell type-specific regulatory programs. ScRNA-seq data is severely affected by dropout, which significantly hampers and restrains current downstream analysis. Although newly developed tools are capable to deal with sparse data, no appropriate single-cell network inference workflow has been established. A potential way to end this deadlock is the application of data imputation methods, which already proofed to be useful in specific contexts of single-cell data analysis, e.g., recovering cell clusters. In order to infer cell-type specific networks, two prerequisites must be met: the identification of cluster-specific cell-types and the network inference itself.Here, we propose a benchmarking framework to investigate both objections. By using suitable reference data with inherent correlation structure, six representative imputation tools and appropriate evaluation measures, we were able to systematically infer the impact of data imputation on network inference. Major network structures were found to be preserved in low dropout data sets. For moderately sparse data sets, DCA was able to recover gene correlation structures, although systematically introducing higher correlation values. No imputation tool was able to recover true signals from high dropout data. However, by using an additional biological data set we could show that cell-cell correlation by means of specific marker gene expression was not compromised through data imputation.Our analysis showed that network inference is feasible for low and moderately sparse data sets by using the unimputed and DCA-prepared data, respectively. High sparsity data, on the other side, still pose a major problem since current imputation techniques are not able to facilitate network inference. The annotation of cluster-specific cell-types as a prerequisite is not hampered by data imputation but their power to restore the deeply hidden correlation structures is still not sufficient enough.
Measuring internal communication satisfaction: validating the internal communication satisfaction questionnaire
Authors: Tkalac Verčič Ana , Sinčić Ćorić Dubravka , Pološki Vokić Nina 
Published: April 2021

PurposeThe study examines the psychometric properties of internal communication satisfaction questionnaire (ICSQ), an instrument originally developed in Croatian. A need for a contemporary instrument validated among a non-English-speaking population of employees who use English as their second language motivated the authors to translate the scale.Design/methodology/approachICSQ was validated on a sample of 507 employees of a large Croatian subsidiary of a multinational bank, where English is the official corporate language.FindingsICSQ displayed satisfactory levels of psychometric properties, retaining the psychometric properties of the original version of the instrument. A confirmatory factor analysis revealed the acceptable model–data fit of the eight-factor model. Additionally, findings supported the reliability and construct validity of the English version of the instrument. Good internal consistencies of all eight internal communication satisfaction (ICS) dimensions and the total ICSQ and an adequate level of scale homogeneity according to the inter-item and inter-total correlations were found.Research limitations/implicationsIn order to generalize the study’s results to other business areas and industries, the study should be replicated in other contexts. Additionally, construct validity was tested by applying cross-sectional design, and therefore, no conclusion can be drawn on the causal direction of the relationship. Finally, the discriminant validity of ICSQ was not tested and should be examined in future studies.Practical implicationsThe resulting 32-item instrument, in English, can be used for empirical and practical purposes in improving internal communication.Originality/valueThe study confirms that internal communication is a multidimensional construct and should be measured as such.
Towards a well-informed rental housing policy in Ghana: differentiating between critics and non-critics of the rent advance system
Authors: Ehwi Richmond Juvenile , Asante Lewis Abedi , Gavu Emmanuel Kofi 
Published: April 2021

Purpose
In Ghana, the practice of landlords demanding that renters pay rent advance (RA) of between six months and five years is well noted. Surprisingly, renters appear divided into the benefits and drawbacks of the rent advance payment. Ahead of the 2020 general elections, the two leading political parties in Ghana promised to establish a rent assistance scheme to help renters working in the formal and informal sectors and earning regular incomes to pay their RA. This paper aims to scrutinize the differences in the demographic, employment and housing characteristics between the critics and non-critics of the RA payment in Ghana and the factors that predict the likelihood of being a critic of the RA system.

Design/methodology/approach
The study is exploratory and draws empirical data from surveys administered to 327 graduate renters from 13 regions in Ghana. It uses non-parametric and parametric tests, namely, Chi-square goodness-of-fit and T-test to explore these differences between both critics and non-critics of the RA.

Findings
There are statistically significant differences between critics and non-critics in terms of the association between their educational attainment on the one hand and their marital status, employment status and employment sector on the other hand. The research also reveals that monthly expenditures, number of bedrooms and RA period significantly predict the likelihood of being a critic of the RA payment or otherwise.

Practical implications
The study provides evidence which policymakers can draw upon to inform housing policy.

Originality/value
The study is the first to study the housing characteristics of graduate renters and to quantitatively distinguish between critics and non-critics of RA payment in Ghana.
Prevailing theoretical approaches predicting sustainable business models: a systematic review
Authors: Ferreira João J. , Fernandes Cristina I. , Veiga Pedro M. , Hughes Mathew 
Published: April 2021

PurposeThis study aims to map scientific publications, intellectual structure and research trends in the sustainable business model (SBM) field. Specifically, it attempts to (1) identify the fundamental contributions of research in this area of knowledge; and (2) determine the research lines that constitute the most prominent intellectual structure. We leverage these insights to formulate and propose a future research agenda for SBM.Design/methodology/approachThe authors made recourse to the bibliometric, co-citation and cluster analysis techniques. To evaluate potential patterns among articles, we analysed how articles are jointly cited. We further applied hierarchical cluster analysis to the articles and used co-citation analysis to group the interrelated articles into distinct sets.FindingsThe results enable the identification and classification of the prevailing theoretical foci in the domain of SBM: (1) SBM implementation; (2) SBM challenges; (3) institutional SBM; (4) circular SBM; and (5) emerging SBM.Originality/valueThis study identifies, explores, analyses and summarises the main theoretical approaches and themes surrounding SBM research to date, contributing to deepening the literature by identifying the priority areas concerning sustainable business models and encouraging future research of an internationally excellent standard.