bluuebunny/crossref_metadata_2025_split huggingface dataset:
Members of the CUGBP Elav-Like Family of RNA-Binding Proteins are Expressed in Distinct Populations of Primary Sensory Neurons
Authors: Grlickova-Duzevik Eliza , Reimonn Thomas M , Michael Merilla , Tian Tina , Owyoung Jordan , McGrath-Conwell Aidan , Neufeld Peter , Mueth Madison , Molliver Derek C , Ward Patricia Jillian , Harrison Benjamin J 
Published: July 2021

ABSTRACTPrimary sensory Dorsal Root Ganglia (DRG) neurons are diverse, with distinct populations that respond to specific stimuli. Previously, we observed that functionally distinct populations of DRG neurons express mRNA transcript variants with different 3’ untranslated regions (3’UTR’s). 3’UTRs harbor binding sites for interaction with RNA-binding proteins (RBPs) for transporting mRNAs to subcellular domains, modulating transcript stability and regulating the rate of translation. In the current study, analysis of publicly available single-cell RNA-Sequencing (scRNA-Seq) data generated from adult mice revealed that 17 3’UTR-binding RBPs were enriched in specific populations of DRG neurons. This included 4 members of the CUGBP Elav-Like Family (CELF): CELF2 and CELF4 were enriched in peptidergic, CELF6 in both peptidergic and nonpeptidergic and CELF3 in tyrosine hydroxylase-expressing neurons.Immunofluorescence studies confirmed that 60% of CELF4+ neurons are small diameter C fibers and 33% medium diameter myelinated (likely Aδ) fibers and showed that CELF4 is distributed to peripheral termini. Co-expression analyses using transcriptomic data and immunofluorescence revealed that CELF4 is enriched in nociceptive neurons that express GFRA3, CGRP and the capsaicin receptor TRPV1. Re-analysis of published transcriptomic data from macaque DRG revealed a highly similar distribution of CELF members, and re-analysis of single-nucleus RNA sequencing data derived mouse and rat DRG after sciatic injury revealed differential expression of CELFs in specific populations of sensory neurons. We propose that CELF RNA-binding proteins may regulate the fate of mRNAs in populations of nociceptors, and may play a role in pain and/or neuronal regeneration following nerve injury.
Find me if you can: Pre- and Post-hurricane Densities of the Red-bellied Racer (Alsophis rufiventris) on St. Eustatius, and a review of the genus in the Caribbean
Authors: Madden Hannah , Fernández Denny S. , Tremblay Raymond L. , Verdel Kevin , Kaboord Brent 
Published: July 2021

ABSTRACTWe estimated population densities of the red-bellied racer (Alsophis rufiventris) on the Caribbean island of St. Eustatius in 2011, 2018 and 2019 to determine the likely influence of hurricanes Irma and Maria (September 2017), in addition to evaluating abiotic parameters which may be correlated with its presence. Surveys were conducted at seven sites in 2011 prior to the hurricanes, and at 81 and 108 sites in 2018 and 2019 respectively posterior to the hurricanes. A total of 8.2 ha was surveyed in 2011, and 11.42 ha in 2018/2019. The pre-hurricane (2011) racer density estimate was 9.2/ha (min 7.3 - max 11.6); post-hurricane estimates were 4.6/ha (min 3.4 - max 6.0) in 2018 and 5.0/ha (min 3.8 - max 6.5) in 2019. The pre-hurricane encounter rate of individual racers was 16.0 snakes/hour compared to 0.34 snakes/hour in 2018 and 0.41 snakes/hour in 2019 (post-hurricane). The decrease in encounter rates between 2011 and 2019 implies a negative impact of the hurricanes on racer abundance. Based on calculations of detection probability (0.02 in 2018 and 0.03 in 2019), post-hurricane lambda estimates were 1.82 (95% CI 0.66 - 5.01) in 2018 and 1.60 (95% CI 0.39 - 6.65) snakes/ha in 2019. Given the current small size of the remaining population and the presence of invasive species across the snake’s range, this species could be at risk of local extirpation. We suggest conservation actions such as invasive species management and habitat restoration to enable further recovery.
All-trans retinoic acid induces synaptopodin-dependent metaplasticity in mouse dentate granule cells
Authors: Lenz Maximilian , Eichler Amelie , Kruse Pia , Muellerleile Julia , Deller Thomas , Jedlicka Peter , Vlachos Andreas 
Published: July 2021

ABSTRACTThe vitamin A derivative all-trans retinoic acid (atRA) is a key mediator of synaptic plasticity. Depending on the brain region studied, distinct effects of atRA on excitatory and inhibitory neurotransmission have been reported. However, it remains unclear how atRA mediates brain region-specific effects on synaptic transmission and plasticity. Here, we used intraperitoneal injections of atRA (10 mg/kg) in adult male C57BL/6J mice to study the effects of atRA on excitatory and inhibitory neurotransmission in the mouse fascia dentata. In contrast to what has been reported in other brain regions, no major changes in synaptic transmission were observed in the ventral and dorsal hippocampus 6 hours after atRA administration. Likewise, no evidence for changes in the intrinsic properties of hippocampal dentate granule cells was obtained in the atRA-treated group. Moreover, hippocampal transcriptome analysis revealed no essential changes upon atRA treatment. In light of these findings, we tested for the metaplastic effects of atRA, i.e., for its ability to modulate synaptic plasticity expression in the absence of major changes in baseline synaptic transmission. Indeed, in vivo long-term potentiation (LTP) experiments demonstrated that systemic atRA treatment improves the ability of dentate granule cells to express LTP. The plasticity-promoting effects of atRA were not observed in synaptopodin-deficient mice, thus extending our previous results on the relevance of synaptopodin in atRA-mediated synaptic strengthening in the mouse prefrontal cortex. Taken together, our data show that atRA mediates synaptopodin-dependent metaplasticity in mouse dentate granule cells.
Linguistic modulation of the neural encoding of phonemes
Authors: Kim Seung-Goo , De Martino Federico , Overath Tobias 
Published: July 2021

AbstractSpeech comprehension entails the neural mapping of the acoustic speech signal onto learned linguistic units. This acousto-linguistic transformation is bi-directional, whereby higher-level linguistic processes (e.g., semantics) modulate the acoustic analysis of individual linguistic units. Here, we investigated the cortical topography and linguistic modulation of the most fundamental linguistic unit, the phoneme. We presented natural speech and ‘phoneme quilts’ (pseudo-randomly shuffled phonemes) in either a familiar (English) or unfamiliar (Korean) language to native English speakers while recording fMRI. This allowed us to dissociate the contribution of acoustic vs. linguistic processes towards phoneme analysis. We show that (1) the acoustic analysis of phonemes is modulated by linguistic analysis and (2) that for this modulation both of acoustic and phonetic information need to be incorporated. These results suggest that the linguistic modulation of cortical sensitivity to phoneme classes minimizes prediction error during natural speech perception, thereby aiding speech comprehension in challenging listening situations.
Compound-specific, concentration-independent biophysical properties of sodium channel inhibitor mechanism of action
Authors: Pesti Krisztina , Földi Mátyás C. , Zboray Katalin , Toth Adam V. , Lukacs Peter , Mike Arpad 
Published: July 2021

AbstractWe have developed an automated patch-clamp protocol that allows high information content screening of sodium channel inhibitor compounds. We have observed that individual compounds had their specific signature patterns of inhibition, which were manifested irrespective of the concentration. Our aim in this study was to quantify these properties. Primary biophysical data, such as onset rate, the shift of the half inactivation voltage, or the delay of recovery from inactivation, are concentration-dependent. We wanted to derive compound-specific properties, therefore, we had to neutralize the effect of concentration. This study describes how this is done, and shows how compound-specific properties reflect the mechanism of action, including binding dynamics, cooperativity, and interaction with the membrane phase. We illustrate the method using four well-known sodium channel inhibitor compounds, riluzole, lidocaine, benzocaine, and bupivacaine. Compound-specific biophysical properties may also serve as a basis for deriving parameters for kinetic modeling of drug action. We discuss how knowledge about the mechanism of action may help to predict the frequency-dependence of individual compounds, as well as their potential persistent current component selectivity. The analysis method described in this study, together with the experimental protocol described in the accompanying paper, allows screening for inhibitor compounds with specific kinetic properties, or with specific mechanisms of inhibition.
Adolescent dopamine neurons represent reward differently during action and state guided learning
Authors: McCane Aqilah M. , Wegener Meredyth A. , Faraji Mojdeh , Garcia Maria T. Rivera , Wallin-Miller Kathryn , Costa Vincent D. , Moghaddam Bita 
Published: July 2021

AbstractThe neuronal underpinning of learning cause-and-effect associations in the adolescent brain remains poorly understood. Two fundamental forms of associative learning are Pavlovian (classical) conditioning, where a stimulus is followed by an outcome, and operant (instrumental) conditioning, where outcome is contingent on action execution. Both forms of learning, when associated with a rewarding outcome, rely on midbrain dopamine neurons in the ventral tegmental area (VTA) and substantia nigra (SN). We find that in adolescent male rats, reward-guided associative learning is encoded differently by midbrain dopamine neurons in each conditioning paradigm. Whereas simultaneously recorded VTA and SN adult neurons have a similar phasic response to reward delivery during both forms of conditioning, adolescent neurons display a muted reward response during operant but a profoundly larger reward response during Pavlovian conditioning suggesting that adolescent neurons assign a different value to reward when it is not gated by action. The learning rate of adolescents and adults during both forms of conditioning was similar further supporting the notion that differences in reward response in each paradigm are due to differences in motivation and independent of state versus action value learning. Static characteristics of dopamine neurons such as dopamine cell number and size were similar in the VTA and SN but there were age differences in baseline firing rate, stimulated release and correlated spike activity suggesting that differences in reward responsiveness by adolescent dopamine neurons are not due to differences in intrinsic properties of these neurons but engagement of different networks.
Microglia and border-associated mouse macrophages maintain their embryonic origin during Alzheimer’s disease
Authors: Wu Xiaoting , Saito Takashi , Saido Takaomi C. , Barron Anna M. , Ruedl Christiane 
Published: July 2021

AbstractBrain microglia and border-associated macrophages (BAMs) display distinct spatial, developmental, and phenotypic features. Although at steady-state, the origins of distinct brain macrophages are well-documented, the dynamics of their replenishment in neurodegenerative disorders remain elusive, particularly for disease-associated microglia (DAMs) and BAMs. In this study, we conducted a comprehensive fate-mapping analysis of murine microglia and BAMs and their turnover kinetics during Alzheimer’s disease (AD) progression. We used a novel inducible AD mouse model to investigate the contribution of bone marrow cells to the pool of foetal-derived brain macrophages during the development of AD. We demonstrated that microglia and DAMs remain a remarkably stable embryonic-derived population even during the progression of AD pathology, indicating that neither parenchymal macrophage subpopulation originates from, nor are replenished by, monocytes. At the border-associated brain regions, bona fide CD206+ BAMs are minimally replaced by monocytes, and their turnover rates are not accelerated by AD. In contrast, all other myeloid cells are swiftly replenished by bone marrow progenitors. This information further elucidates the turnover kinetics of these cells not only at steady-state, but also in neurodegenerative diseases, which is crucial for identifying potential novel therapeutic targets.Impact statementInducible fate-mapping analysis demonstrates that neither microglia, disease-associated microglia nor border-associated macrophages are replenished by bone marrow-derived cells in Alzheimer’s disease.
Sexually distinct song cultures in a songbird metapopulation
Authors: Webb Wesley H. , Roper Michelle M. , Pawley Matthew D. , Fukuzawa Yukio , Harmer Aaron M. , Brunton Dianne H. 
Published: July 2021

AbstractSongbirds learn their songs culturally, through imitating tutors. The vocal culture of a songbird population changes as new song units (syllables) are introduced through immigration, copying errors, and innovation, while other syllables fall out of use. This leads to a diversification of the syllable pool across the species, much like the diversification and spatial patterns of human language. Vocal cultures have been well studied in male songbirds but have been largely overlooked in females. In particular, few studies compare spatial variation of male and female song cultures. Here we undertake one of the first comparisons of male and female song culture in birds, analysing song data from a metapopulation of New Zealand bellbirds Anthornis melanura, spanning an archipelago of six islands. Having classified 20,700 syllables, we compare population syllable repertoire sizes and overlap between sites and sexes. We show that males and females—both with complex songs—have distinct song cultures, sharing only 6–26% of syllable types within each site. Furthermore, male and female syllable types can be statistically discriminated based on acoustic properties. Despite diverse syllable repertoires within sites, few syllable types were shared between sites (both sexes had highly distinct site-specific dialects). For the few types shared between sites, sharing decreased with distance only for males. Overall, there was no significant difference between sexes in degree of site–site repertoire overlap. These results suggest different cultural processes at play for the two sexes, underlining the inadequacy of male-centric song research and calling for comparisons of male and female song cultures in many more species.
Algorithms for the discovery of cis-eQTL signals in woody species: the vine (Vitis viniferaL.) as a study model
Authors: Martínez-García Pedro José , Mas-Gómez J , Wegrzyn Jill , Botía Juan A. 
Published: July 2021

AbstractExpression quantitative trait loci (eQTLs), are associations between genetic variants, such as Single Nucleotide Polymorphisms (SNPs), and gene expression. eQTLs are an important tool to understand the genetics of gene expression of complex phenotypes. eQTLs analysis are common in human studies and in model species such as mice, rats and yeast but are very scarce in wood crop species such as fruit trees or grapevines. In this study a comprehensive bioinformatic pipeline has been carried out using genomics and expression data from 10 genotypes of grape, which has been used as model species. As a result of this study a total of 10,618 genetic variants that regulate gene expression levels of 525 genes were detected. A 78% of them, 411, received a functional annotation from UniProtKB or DAVID, between the annotated protein-coding genes are Germin-like proteins (GLPs), auxin-regulatory factors, GRFS, ANK_REP_REGION domain-containing protein, Kinesin motor domain-containing protein or RPP13like protein 2(LOC100852873). This new inventory of cis eQTLs influencing gene expression during the ripening of fruits ofVitis viniferaL. will be an important resource for future research to understand the mechanistic basis for variation in gene regulation in this species. In the future, this methodology may be applied to other woody species, once the necessary databases are generated.
Irisin stimulates the release of CXCL1 from differentiating human subcutaneous and deep-neck derived adipocytes via upregulation of NFκB pathway
Authors: Shaw Abhirup , Tóth Beáta B , Király Róbert , Arianti Rini , Csomós István , Póliska Szilárd , Vámos Attila , Korponay-Szabó Ilma R , Bacso Zsolt , Győry Ferenc , Fésüs László , Kristóf Endre 
Published: July 2021

AbstractThermogenic brown and beige adipocytes play an important role in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed “batokines”. Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primarily during exercise. We performed global RNA sequencing on adipocytes derived from human subcutaneous and deep-neck precursors, which were differentiated in the presence or absence of irisin. Irisin did not exert an effect on the expression of characteristic thermogenic genes, while upregulated genes belonging to various cytokine signaling pathways. Out of the several upregulated cytokines,CXCL1, the highest upregulated, was released throughout the entire differentiation period, and predominantly by differentiated adipocytes. Deep-neck area tissue biopsies also showed a significant release of CXCL1 during 24 hours irisin treatment. Gene expression data indicated upregulation of the NFкB pathway upon irisin treatment, which was validated by an increase of p50 and decrease of IкBα protein level, respectively. Continuous blocking of the NFκB pathway, using a cell permeable inhibitor of NFκB nuclear translocation, significantly reduced CXCL1 release. The released CXCL1 exerted a positive effect on the adhesion of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel “batokine”, CXCL1, via upregulation of NFκB pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization.
Identification of the cell-type-specific ER membrane protein Tanmp expressed in hypothalamic tanycytes and subsets of neurons
Authors: Takahashi Osamu , Tanahashi Mayuko , Yokoi Saori , Kaneko Mari , Tokuhara Tomoko , Yanaka Kaori , Nakagawa Shinichi , Maita Hiroshi 
Published: July 2021

AbstractGenomes of higher eukaryotes encode many uncharacterized proteins, and the functions of these proteins cannot be predicted from the primary sequences due to a lack of conserved functional domains. During a screening of novel noncoding RNAs abundantly expressed in mouse brains, we incidentally identified a gene termed Tanmp, which encoded an endoplasmic reticulum (ER) protein without known functional domains. Tanmp is specifically expressed in the nervous system, and the highest expression was observed in a specialized cell type called tanycyte that aligns the ventral wall of the third ventricle in the hypothalamus. Immunostaining of Tanmp revealed the fine morphology of tanycytes with highly branched apical ER membranes. Immunoprecipitation revealed that Tanmp associates with mitochondrial ATPase at least in vitro, and ER and mitochondrial signals occasionally overlapped in tanycytes. Mutant mice lacking Tanmp did not exhibit overt phenotypes, suggesting that Tanmp is not essential in mice reared under normal laboratory conditions. We also found that RNA probes that are predicted to uniquely detect Tanmp mRNA cross-reacted with uncharacterized RNAs, highlighting the importance of experimental validation of the specificity of probes during the hybridization-based study of RNA localization.
Glial place cells: complementary encoding of spatial information in hippocampal astrocytes
Authors: Curreli Sebastiano , Bonato Jacopo , Romanzi Sara , Panzeri Stefano , Fellin Tommaso 
Published: July 2021

AbstractCalcium dynamics into astrocytes influence the activity of nearby neuronal structures. However, because previous reports show that astrocytic calcium signals largely mirror neighboring neuronal activity, current information coding models neglect astrocytes. Using simultaneous two-photon calcium imaging of astrocytes and neurons in the hippocampus of mice navigating a virtual environment, we demonstrate that astrocytic calcium signals actively encode spatial information. Calcium events carrying spatial information occurred in topographically organized astrocytic subregions. Importantly, astrocytes encoded spatial information that was complementary and synergistic to that carried by neurons, improving spatial position decoding when astrocytic signals were considered alongside neuronal ones. These results suggest that the complementary place-dependence of localized astrocytic calcium signals regulates clusters of nearby synapses, enabling dynamic, context-dependent, variations in population coding within brain circuits.
Current-account breaks and stability spells in a global perspective
Authors: Camba-Crespo Alfonso , García-Solanes José , Torrejón-Flores Fernando 
Published: July 2021

PurposeThis study aims to identify structural breaks in the current account and the periods between these breaks, which the authors name stability spells, and study their characteristics and determinants.Design/methodology/approachUsing data from the IMF and the World Bank, this study applies the Lee and Strazicich test to endogenously identify breaks and the Heckman selection model to simultaneously study the determinants of structural breaks and current-account changes after breaks.FindingsThis study identifies 212 significant structural breaks and 341 stability spells. These spells become shorter and more volatile the further they are from equilibrium, and half of them last 10 years or less. The results show that economic growth and foreign-exchange piling are particularly useful to prevent breaks, while lower per capita income increases exposure to break risks.Originality/valueThis study introduces the concept of current-account stability spells to refer to the periods between structural breaks. These spells are then studied to determine their main characteristics. The authors also apply a global perspective in their analysis, using a wide sample of 181 economies between 1980 and 2018 and considering positive and negative breaks in both level and trend.