bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced negative emotional processing limits behavioral flexibility in a mouse model of autism spectrum disorder
Authors: Yun Miru , Kim Eunjoon , Jung Min Whan 
Published: June 2021

AbstractImpaired behavioral flexibility might underlie some of the symptoms associated with autism spectrum disorder (ASD). We investigated whether and how behavioral flexibility is impaired in a mouse model of ASD by testing Shank2-knockout (Shank2-KO) mice in reversal learning. Shank2-KO mice were trained in probabilistic classical conditioning with two odor cues paired with water and air puff. Upon the reversal of cue-outcome contingency, Shank2-KO mice were significantly slower than wild-type mice in reversing their anticipatory licking responses. Shank2-KO mice also showed stronger anticipatory eye closure responses than wild-type mice to the air puff, raising a possibility that the impairment might be because of enhanced negative emotional processing. Indeed, Shank2-KO mice showed intact reversal learning when the strong air puff was replaced with a mild air puff. Shank2-KO mice also showed intact reversal learning between two odor cues predicting rewards with different probabilities. These results indicate that enhanced negative emotional processing suppresses reversal learning despite of intact capability to learn cue-outcome contingency changes in Shank2-KO mice in our behavioral settings. Our findings suggest that behavioral flexibility may be seriously limited by abnormal emotional processing in ASD.
The role of obesity in female reproductive conditions: A Mendelian Randomisation study
Authors: Venkatesh Samvida S. , Ferreira Teresa , Benonisdottir Stefania , Rahmioglu Nilufer , Becker Christian M. , Granne Ingrid , Zondervan Krina T. , Holmes Michael V. , Lindgren Cecilia M. , Wittemans Laura B. L. 
Published: June 2021

AbstractBackgroundObesity is observationally associated with altered risk of many female reproductive conditions. These include polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, infertility, and pregnancy-related disorders. However, the roles and mechanisms of obesity in the aetiology of reproductive disorders remain unclear.Methods and FindingsWe estimated observational and genetically predicted causal associations between obesity, metabolic hormones, and female reproductive conditions using logistic regression, generalised additive models, and Mendelian randomisation (two-sample, non-linear, and multivariable) applied to data from UK Biobank and publicly available genome-wide association studies (GWAS).Body mass index (BMI), waist-hip ratio (WHR), and WHR adjusted for BMI (WHRadjBMI) were observationally (odds ratios (ORs) = 1.02 – 1.87 per 1 S.D. obesity trait) and causally (ORs = 1.06 – 2.09) associated with uterine fibroids (UF), PCOS, heavy menstrual bleeding (HMB), and pre-eclampsia. Causal effect estimates of WHR and WHRadjBMI, but not BMI, were attenuated compared to their observational counterparts. Genetically predicted visceral adipose tissue mass was causal for the development of HMB, PCOS, and pre-eclampsia (ORs = 1.01 - 3.38). Increased waist circumference also posed a higher causal risk (ORs = 1.16 – 1.93) for the development of these disorders and UF than did increased hip circumference (ORs = 1.06 – 1.10). Leptin, fasting insulin, and insulin resistance each mediated between 20% -50% of the total causal effect of obesity on pre-eclampsia. Reproductive conditions clustered based on shared genetic components of their aetiological relationships with obesity.ConclusionsIn this first systematic, large-scale, genetics-based analysis of the aetiological relationships between obesity and female reproductive conditions, we found that common indices of overall and central obesity increased risk of reproductive disorders to heterogenous extents, mediated by metabolic hormones. Our results suggest exploring the mechanisms mediating the causal effects of overweight and obesity on gynaecological health to identify targets for disease prevention and treatment.
Arousal-dependent auditory responses in the brain of Bengalese finches measured by gene expression
Authors: Iizuka Takafumi , Mori Chihiro , Okanoya Kazuo 
Published: June 2021

AbstractSongbirds use auditory feedback to maintain their own songs. Juveniles also memorize a tutor song and use memory as a template to make up their own songs through auditory feedback. A recent electrophysiological study revealed that HVC neurons respond to BOS playback only in low arousal, sleeping, or anesthetized conditions. One outstanding question is how does auditory suppression occur in the brain? Here, we determined how arousal affects auditory responses simultaneously in the whole brain and over the song neural circuit in Bengalese finches, using the immediate early gene egr-1 as a marker of neural activity. Our results showed that auditory responses in the low-arousal state were less susceptible to gating, which was also confirmed by gene expression, and that the suppression may be weaker than observed in previous zebra finch studies. This may be because the Bengalese finch is a domesticated species. In addition, our results suggest that information may flow from the MLd.I of the midbrain to higher auditory regions. Altogether, this study presents a new attempt to explore the auditory suppression network by simultaneously investigating the whole brain using molecular biology methods.
Distinct spatiotemporal contribution of morphogenetic events and mechanical tissue coupling during Xenopus neural tube closure
Authors: Christodoulou Neophytos , Skourides Paris A. 
Published: June 2021

AbstractNeural tube closure (NTC) is a fundamental process during vertebrate embryonic development and is indispensable for the formation of the central nervous system. Here, using Xenopus laevis embryos, live imaging, single cell tracking, optogenetics and loss of function experiments we examine the contribution of convergent extension (CE) and apical constriction (AC) and we define the role of the surface ectoderm (SE) during NTC. We show that NTC is a two-stage process and that CE and AC do not overlap temporally while their spatial activity is distinct. PCP driven CE is restricted to the caudal part of the neural plate (NP) and takes place during the first stage. CE is essential for correct positioning of the NP rostral most region in the midline of the dorsoventral axis. AC occurs after CE throughout the NP and is the sole contributor of anterior NTC. We go on to show that the SE is mechanically coupled with the NP providing resistive forces during NTC. Its movement towards the midline is passive and driven by forces generated through NP morphogenesis. Last, we show that increase of SE resistive forces is detrimental for NP morphogenesis, showing that correct SE development is permissive for NTC.
Brief exposure of neuronal cells to levels of short chain fatty acids observed in human systemic circulation impair the cell lipid metabolism resulting in associated cell death by apoptosis
Authors: Fillier Tiffany A. , Shah Shrushti , Doody Karen M. , Pham Thu H. , Aubry Isabelle , Tremblay Michel L. , Cheema Sukhinder K. , Blundell Jacqueline , Thomas Raymond H. 
Published: June 2021

AbstractCommunication between gut microbiota and the brain is an enigma. Alterations in the gut microbial community affects enteric metabolite levels, such as SCFAs. SCFAs have been proposed as a possible mechanism through which the gut microbiome modulate brain health and function. This study analyzed for the first time the effects of SCFAs at levels reported in human systemic circulation on human neuronal cell energy metabolism, viability, survival and the brain lipidome. Cell and rat brain lipidomics was done using UHPLC-HESI-HRAMS/MS. Neuronal cells viability, survival and energy metabolism were analyzed via flow cytometer, immunofluorescence, and SeahorseXF platform. Lipidomics analysis demonstrated that SCFAs significantly remodeled the brain lipidome in vivo and in vitro. The most notable remodulation was observed in the metabolism of phosphatidylethanolamine plasmalogens, and mitochondrial lipids carnitine and cardiolipin. Increased mitochondrial mass, fragmentation, and hyperfusion occurred concomitant with the altered mitochondrial lipid metabolism resulting in decreased neuronal cell respiration, ATP production, and increased cell death. This suggests SCFAs at levels observed in human systemic circulation can adversely alter the brain lipidome and neuronal cell function potentially negatively impacting brain health outcomes.
Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts
Authors: Gulyaeva Anastasia , Garmaeva Sanzhima , Ruigrok Renate A.A.A. , Wang Daoming , Riksen Niels P. , Netea Mihai G. , Wijmenga Cisca , Weersma Rinse K. , Fu Jingyuan , Vila Arnau Vich , Kurilshikov Alexander , Zhernakova Alexandra 
Published: June 2021

SummaryThe crAss-like phages are a diverse group of related viruses that includes one of the most abundant viruses of the human gut. To explore their diversity and functional role in human population and clinical cohorts, we analyzed gut metagenomic data collected from more than 2000 individuals from the Netherlands. We discovered 125 novel species-level and 32 novel genus-level clusters of crAss-like phages, all belonging to five previously recognized groups associated with the human gut. Analysis of their genomic features revealed that closely related crAss-like phages can possess strikingly divergent regions responsible for transcription, presumably acquired through recombination. Prediction of crAss-like phage hosts pointed primarily to bacteria of the phylum Bacteroidetes, consistent with previous reports. Finally, we explored the temporal stability of crAss-like phages over a 4-year period and identified associations between the abundance of crAss-like phages and several human phenotypes, including depletion of crAss-like phages in inflammatory bowel disease patients.Highlights125 tentative new species of crAss-like phages were discoveredClosely related crAss-like phages often possess highly divergent transcription gene modules possibly acquired via recombinationCrAss-like fraction of the human gut virome remains relatively stable over the period of 4 yearsPrevalence of crAss-like phages in the human gut is associated with several metabolic, dietary and health phenotypesGut crAss-like phages are depleted in inflammatory bowel disease patients
The draft chromosome-level genome assembly of tetraploid ground cherry (Prunus fruticosa Pall.) from long reads
Authors: Wöhner Thomas W. , Emeriewen Ofere F. , Wittenberg Alexander H.J. , Schneiders Harrie , Vrijenhoek Ilse , Halász Júlia , Hrotkó Károly , Hoff Katharina J. , Gabriel Lars , Keilwagen Jens , Berner Thomas , Schuster Mirko , Peil Andreas , Wünsche Jens , Kropop Stephan , Flachowsky Henryk 
Published: June 2021

AbstractBackgroundCherries are stone fruits and belong to the economically important plant family of Rosaceae with worldwide cultivation of different species. The ground cherry, Prunus fruticosa Pall. is one ancestor of cultivated sour cherry, an important tetraploid cherry species. Here, we present a long read chromosome-level draft genome assembly and related plastid sequences using the Oxford Nanopore Technology PromethION platform and R10.3 pore type.FindingThe final assemblies obtained from 117.3 Gb cleaned reads representing 97x coverage of expected 1.2 Gb tetraploid (2n=4x=32) and 0.3 Gb haploid (1n=8) genome sequence of P. fruticosa were calculated. The N50 contig length ranged between 0.3 and 0.5 Mb with the longest contig being ∼6 Mb. BUSCO estimated a completeness between 98.7 % for the 4n and 96.1 % for the 1n datasets.Using a homology and reference based scaffolding method, we generated a final consensus genome sequence of 366 Mb comprising eight chromosomes. The N50 scaffold was ∼44 Mb with the longest chromosome being 66.5 Mb.The repeat content was estimated to ∼190 Mb (52 %) and 58,880 protein-coding genes were annotated. The chloroplast and mitochondrial genomes were 158,217 bp and 383,281 bp long, which is in accordance with previously published plastid sequences.ConclusionThis is the first report of the genome of ground cherry (P. fruticosa) sequenced by long read technology only. The datasets obtained from this study provide a foundation for future breeding, molecular and evolutionary analysis in Prunus studies.
Phenotypic and transcriptomic analyses reveal major differences between apple and pear scab nonhost resistance
Authors: Vergne Emilie , Chevreau Elisabeth , Ravon Elisa , Gaillard Sylvain , Pelletier Sandra , Bahut Muriel , Perchepied Laure 
Published: June 2021

AbstractNonhost resistance is the outcome of most plant/pathogen interactions, but it has rarely been described in Rosaceous fruit species. Apple (Malus x domesticaBorkh.) have a nonhost resistance toVenturia pyrina, the scab species attacking European pear (Pyrus communisL.). Reciprocally,P. communishave a nonhost resistance toVenturia inaequalis, the scab species attacking apple. The major objective of our study was to compare the scab nonhost resistance in apple and in European pear, at the phenotypic and transcriptomic levels. Macro- and microscopic observations after reciprocal scab inoculations indicated that, after a similar germination step, nonhost apple/V. pyrinainteraction remained nearly symptomless, whereas more hypersensitive reactions were observed during nonhost pear/V. inaequalisinteraction. Comparative transcriptomic analyses of apple and pear nonhost interactions withV. pyrinaandV. inaequalis, respectively, revealed differences. Very few differentially expressed genes were detected during apple/V. pyrinainteraction, preventing the inferring of underlying molecular mechanisms. On the contrary, numerous genes were differentially expressed during pear/V. inaequalisinteraction, allowing a deep deciphering. Pre-invasive defense, such as stomatal closure, could be inferred, as well as several post-invasive defense mechanisms (apoplastic reactive oxygen species accumulation, phytoalexin production and alterations of the epidermis composition). In addition, a comparative analysis between pear scab host and nonhost interactions indicated that, although specificities were observed, two major defense lines seems to be shared in these resistances: cell wall and cuticle potential modifications and phenylpropanoid pathway induction. This first deciphering of the molecular mechanisms underlying a nonhost scab resistance in pear offers new possibilities for the genetic engineering of sustainable scab resistance in this species. Concerning nonhost scab resistance in apple, further analyses must be considered with the aid of tools adapted to this resistance with very few cells engaged.
Ciliated protozoa from industrial WWTP activated sludge: a biodiversity survey including trophic interactions and redescription ofBakuella subtropica(Spirotrichea, Hypotrichia) according to Next Generation Taxonomy
Authors: Liao Wanying , Serra Valentina , Gammuto Leandro , Spennati Francesco , Mori Gualtiero , Munz Giulio , Modeo Letizia , Petroni Giulio 
Published: June 2021

SummaryOptimization of wastewater treatment with biological processes is a fundamental challenge of modern society. During past years new technologies have been developed for the purpose and prokaryotic organisms involved in the process extensively investigated. Nevertheless, relatively few studies so far analysed the protozoan community in these systems using modern integrative approaches, despite its obvious role in shaping ecological dynamics and, possibly, process efficiency. In the present study, we characterized the ciliate community in biological reactors of an Italian industrial (tannery) wastewater treatment plant (WWTP) applying modified Ludzack-Ettinger (MLE) process. This plant is characterized by moderate salinity, high solids retention time and high concentration of organic compounds, including a significant recalcitrant fraction. We performed the morphological and 18S rDNA characterizations of almost all the 21 ciliates retrieved along a one-year sampling period, and provided preliminary data on species occurrence, community dynamics, and trophic interactions. Only 16 species were observed on the sample collection day and most of them had an occurrence higher than 50%. The most frequently occurring and highly abundant organisms wereAspidiscacf.cicada,Euplotesspp.,Paramecium calkinsi, andPhialinasp.Cyclidiumcf.marinumwas only found on a single date and its presence was possibly related to a summer break-induced perturbation. All the species showed the capability to survive the short oxic/anoxic cycling typical of the studied WWTP process. Intriguingly, some of them (i.e.,Bakuella subtropicaandTrochiliopsis australis) turned out to be species isolated from brackish natural environment rich in organic load as well. As forB. subtropica, we provided an emended redescription according to the most recent taxonomy standards that include also mitogenomic sequencing.
SynergyFinder Plus: Toward Better Interpretation and Annotation of Drug Combination Screening Datasets
Authors: Zheng Shuyu , Wang Wenyu , Aldahdooh Jehad , Malyutina Alina , Shadbahr Tolou , Tanoli Ziaurrehman , Pessia Alberto , Tang Jing 
Published: June 2021

AbstractCombinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The SynergyFinder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report the major updates to the SynergyFinder R package for improved interpretation and annotation of drug combination screening results. Unlike the existing implementations, the updated SynergyFinder R package includes five main innovations. (1) We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape. (2) We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values. (3) We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy. (4) We evaluate drug combination synergy and sensitivity to provide an unbiased interpretation of the clinical potential. (5) We enable fast annotation of drugs and cell lines, including their chemical and target information. These annotations will improve the interpretation of the mechanisms of action of drug combinations. To facilitate the use of the R package within the drug discovery community, we also provide a web server at www.synergyfinderplus.org as a user-friendly interface to enable a more flexible and versatile analysis of drug combination data.
Attention Networks and the Intrinsic Network Structure of the Human Brain
Authors: Markett Sebastian , Nothdurfter David , Focsa Antonia , Reuter Martin , Jawinski Philippe 
Published: June 2021

AbstractAttention network theory states that attention is not a unified construct but consists of three independent systems that are supported by separable distributed networks: an alerting network to deploy attentional resources in anticipation of upcoming events, an orienting network to direct attention to a cued location, and a control network to select relevant information at the expense of concurrently available information. Ample behavioral and neuroimaging evidence supports the dissociation of the three attention domains. The strong assumption that each attentional system is realized through a separable network, however, raises the question how these networks relate to the intrinsic network structure of the brain.Our understanding of brain networks has advanced majorly in the past years due to the increasing focus on brain connectivity. It is well established that the brain is intrinsically organized into several large-scale networks whose modular structure persists across task states. Existing proposals on how the presumed attention networks relate to intrinsic networks rely mostly on anecdotal and partly contradictory arguments. We addressed this issue by mapping different attention networks with highest spatial precision at the level of cifti-grayordinates. Resulting group maps were compared to the group-level topology of 23 intrinsic networks which we reconstructed from the same participants’ resting state fMRI data. We found that all attention domains recruited multiple and partly overlapping intrinsic networks and converged in the dorsal fronto-parietal and midcingulo-insular network. While we observed a preference of each attentional domain for its own set of intrinsic networks, implicated networks did not match well to those proposed in the literature. Our results indicate a necessary refinement of the attention network theory.
Song preferences predict the quality of vocal learning in zebra finches
Authors: Rodríguez-Saltos Carlos Antonio , Bhise Aditya , Karur Prasanna , Khan Ramsha Nabihah , Lee Sumin , Ramsay Gordon , Maney Donna L. 
Published: June 2021

AbstractIn songbirds, learning to sing is a highly social process that likely involves social reward. Here, we hypothesized that the degree to which a juvenile songbird learns a song depends on the degree to which it finds that song rewarding to hear during vocal development. We tested this hypothesis by measuring song preferences in young birds during song learning and then analyzing their adult songs. Song preferences were measured in an operant key-pressing assay. Juvenile male zebra finches (Taeniopygia guttata) had access to two keys, each of which was associated with a higher likelihood of playing the song of their father or that of another familiar adult (“neighbor”). To minimize the effects of exposure on learning, we implemented a reinforcement schedule that allowed us to detect preferences while balancing exposure to each song. On average, the juveniles significantly preferred the father’s song early during song learning, before they were themselves singing. At around post-hatch day 60, their preference shifted to the neighbor’s song. At the end of the song learning period, we recorded the juveniles’ songs and compared them to the father’s and the neighbor’s song. All of the birds copied father’s song. The accuracy with which the father’s song was imitated was positively correlated with the peak strength of the preference for the father’s song during the sensitive period. Our results show that preference for a social stimulus, in this case a vocalization, predicted social learning during development.