bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic risk scores for psychiatric, inflammatory, and cardio-metabolic traits and diseases highlight possible genetic overlaps with suicide attempt and treatment-emergent suicidal ideation
Authors: Fanelli Giuseppe , Sokolowski Marcus , Wasserman Danuta ,   European College of Neuropsychopharmacology (ECNP) Network on Suicide Research and Prevention, Kasper Siegfried , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Forloni Gianluigi , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Ronchi Diana De , Serretti Alessandro , Fabbri Chiara 
Published: March 2021

AbstractSuicide is the second leading cause of death among young people. Genetics may contribute to suicidal phenotypes and their co-occurrence in other psychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 22 psychiatric, inflammatory, and cardio-metabolic traits and diseases with suicide attempt (SA) or treatment-worsening/emergent suicidal ideation (TWESI).PRSs were computed based on summary statistics of genome-wide association studies. Regression analyses were performed between PRSs and SA or TWESI in four clinical cohorts, including up to 3,834 individuals, and results were meta-analyzed across samples. Stratified genetic covariance analyses were performed to investigate the biology underlying cross-phenotype PRS associations. After Bonferroni correction, PRS for major depressive disorder (MDD) was positively associated with SA (p=1.7e-4). Nominal associations were shown between PRSs for coronary artery disease (CAD) (p=4.6e-3) or loneliness (p=0.009) and SA, PRSs for MDD or CAD and TWESI (p=0.033 and p=0.032, respectively). Genetic covariance between MDD and SA was shown in 35 gene sets related to drugs having anti-suicidal effects.A higher genetic liability for MDD may underlie a higher risk of SA. Further, but milder, possible modulatory factors are genetic risk for loneliness and CAD.
Evolutionary dynamics of the OR gene repertoire in teleost fishes: evidence of an association with changes in olfactory epithelium shape
Authors: Policarpo Maxime , Bemis Katherine E , Tyler James C , Metcalfe Cushla J , Laurenti Patrick , Sandoz Jean-Christophe , Rétaux Sylvie , Casane Didier 
Published: March 2021

AbstractTeleost fishes perceive their environment through a range of sensory modalities, among which olfaction often plays an important role. Richness of the olfactory repertoire depends on the diversity of receptors coded by homologous genes classified into four families: OR, TAAR, VR1 and VR2. Herein, we focus on the OR gene repertoire. While independent large contractions of the OR gene repertoire associated with ecological transitions have been found in mammals, little is known about the diversity of the OR gene repertoire and its evolution within teleost fishes, a group that includes more than 34,000 living species. We analyzed genomes of 163 species representing diversity in this large group. We found a large range of variation in the number of functional OR genes, from 15 inSyngnathus typhleandMola mola, to 429 inMastacembelus armatus. The number of OR genes was higher in species with an extensively folded olfactory epithelium, that is, for example, when a multi-lamellar rosette was present in the olfactory organ. Moreover, the number of lamellae was correlated with the richness of the OR gene repertoire. While a slow and balanced birth-and-death process generally drives evolution of the OR gene repertoire, we inferred several episodes of high rates of gene loss, sometimes followed by large gains in the number of OR genes. These gains coincide with morphological changes of the olfactory organ and suggest a strong functional association between changes in the morphology and the evolution of the OR gene repertoire.
Mapping of Whole-Brain Resting-State Networks with Half-Millimetre Resolution
Authors: Yun Seong Dae , Pais-Roldán Patricia , Palomero-Gallagher Nicola , Shah N. Jon 
Published: March 2021

AbstractResting-state fMRI has been used in numerous studies to map networks in the brain that employ spatially disparate regions. However, attempts to map networks with high spatial resolution have been hampered by conflicting technical demands and associated problems. Results from recent fMRI studies have shown that spatial resolution remains around 0.7 × 0.7 × 0.7 mm3, with only partial brain coverage. This work presents a novel fMRI method, TR-external EPI with keyhole (TR-external EPIK), which can provide a nominal spatial resolution of 0.51 × 0.51 × 1.00 mm3(0.26 mm3voxel) with whole-brain coverage. TR-external EPIK enabled the identification of various resting-state networks distributed throughout the brain from a single fMRI session, with mapping fidelity onto the grey matter at 7T. The high-resolution functional image further revealed mesoscale anatomical structures, such as small cerebral vessels and the internal granular layer of the cortex within the postcentral gyrus.
MinION barcodes: biodiversity discovery and identification by everyone, for everyone
Authors: Srivathsan Amrita , Lee Leshon , Katoh Kazutaka , Hartop Emily , Kutty Sujatha Narayanan , Wong Johnathan , Yeo Darren , Meier Rudolf 
Published: March 2021

AbstractBackgroundDNA barcodes are a useful tool for discovering, understanding, and monitoring biodiversity which are critical tasks at a time of rapid biodiversity loss. However, widespread adoption of barcodes requires cost-effective and simple barcoding methods. We here present a workflow that satisfies these conditions. It was developed via “innovation through subtraction” and thus requires minimal lab equipment, can be learned within days, reduces the barcode sequencing cost to <10 cents, and allows fast turnaround from specimen to sequence by using the portable, real-time sequencer MinION.ResultsWe describe cost-effective and rapid procedures for barcoding individual specimens with MinION sequencing. We illustrate how tagged amplicons can be obtained and sequenced with the portable, real-time MinION sequencer in many settings (field stations, biodiversity labs, citizen science labs, schools). We also provide amplicon coverage recommendations that are based on several runs of the latest generation of MinION flow cells (“R10.3”) which suggest that each run can generate barcodes for >10,000 specimens. Next, we present a novel software, ONTbarcoder, which overcomes the bioinformatics challenges posed by MinION reads. The software is compatible with Windows 10, Macintosh, and Linux, has a graphical user interface (GUI), and can generate thousands of barcodes on a standard laptop within hours based on only two input files (FASTQ, demultiplexing file). We document that MinION barcodes are virtually identical to Sanger and Illumina barcodes for the same specimens (>99.99%) and provide evidence that MinION flow cells and reads have improved rapidly since 2018.ConclusionsWe propose that barcoding with MinION is the way forward for government agencies, universities, museums, and schools because it combines low consumable and capital cost with scalability. Small projects can use the flow cell dongle (“Flongle”) while large projects can rely on MinION flow cells that can be stopped and re-used after collecting sufficient data for a given project.
Establishing farm dust as a useful viral metagenomic surveillance matrix
Authors: Kwok Kirsty T. T. , de Rooij Myrna M. T. , Messink Aniek B. , Wouters Inge M. , Smit Lidwien A. M. , Cotten Matthew , Heederik Dick J.J. , Koopmans Marion P. G. , Phan My V. T. 
Published: March 2021

ABSTRACTFarm animals may harbor viral pathogens, some with zoonotic potential which can possibly cause severe clinical outcomes in animals and humans. Documenting the viral content of dust may provide information on the potential sources and movement of viruses. Here, we describe a dust sequencing strategy that provides detailed viral sequence characterization from farm dust samples and use this method to document the virus communities from chicken farm dust samples and paired feces collected from the same broiler farms in the Netherlands. From the sequencing data,ParvoviridaeandPicornaviridaewere the most frequently found virus families, detected in 85-100% of all fecal and dust samples with a large genomic diversity identified from thePicornaviridae. Sequences from theCaliciviridaeandAstroviridaefamiles were also obtained. This study provides a unique characterization of virus communities in farmed chickens and paired farm dust samples and our sequencing methodology enabled the recovery of viral genome sequences from farm dust, providing important tracking details for virus movement between livestock animals and their farm environment. This study serves as a proof of concept supporting dust sampling to be used in viral metagenomic surveillance.
A Focused Small-Molecule Screen Identifies PHA-680626 as an Amphosteric Inhibitor Disrupting the Interaction between Aurora-A and N-Myc
Authors: Souvalidou Fani , Boi Dalila , Montanari Roberta , Polverino Federica , Marini Grazia , Capelli Davide , Pochetti Giorgio , Contestabile Roberto , Trisciuoglio Daniela , Tramonti Angela , Carpinelli Patrizia , Ascanelli Camilla , Lindon Catherine , De Leo Alessandro , Di Santo Roberto , Costi Roberta , Guarguaglini Giulia , Paiardini Alessandro 
Published: March 2021

ABSTRACTNeuroblastoma is a severe childhood disease, accounting for ~10% of all infant cancers. The amplification of the MYCN gene, coding for the N-Myc transcriptional factor, is an essential marker correlated with tumor progression and poor prognosis. In neuroblastoma cells, the mitotic kinase Aurora-A (AURKA), also frequently overexpressed in cancer, prevents N-Myc degradation, by directly binding to a highly conserved N-Myc region, i.e. Myc Box I. As a result, elevated levels of N-Myc, which are required for the growth of MYCN amplified cells, are observed. During the last years, it has been demonstrated that the ATP competitive inhibitors of AURKA CD532, MLN8054 and Alisertib also cause essential conformational changes in the structure of the activation loop of the kinase that prevent N-Myc binding, thus impairing the formation of the AURKA/N-Myc complex. In this study, starting from a screening of crystal structures of AURKA in complex with known inhibitors, we identified additional compounds affecting the conformation of the kinase activation loop. We assessed the ability of such compounds to disrupt the interaction between AURKA and N-Mycin vitro, using Surface Plasmon Resonance competition assays, and in tumor cell lines overexpressing MYCN, by performing Proximity Ligation Assays. Finally, their effects on N-Myc cellular levels and cell viability were investigated. Our results, identifying PHA-680626 as an amphosteric inhibitor bothin vitroand MYCN overexpressing cell lines, expand the repertoire of known conformational disrupting inhibitors of the AURKA/N-Myc complex, and confirm that altering the conformation of the activation loop of AURKA with a small molecule is an effective strategy to destabilize the AURKA/N-Myc interaction in neuroblastoma cancer cells.
PhyloCSF++: A fast and user-friendly implementation of PhyloCSF with annotation tools
Authors: Pockrandt Christopher , Steinegger Martin , Salzberg Steven L. 
Published: March 2021

AbstractSummaryPhyloCSF++ is an efficient and parallelized C++ implementation of the popular PhyloCSF method to distinguish protein-coding and non-coding regions in a genome based on multiple sequence alignments. It can score alignments or produce browser tracks for entire genomes in the wig file format. Additionally, PhyloCSF++ annotates coding sequences in GFF/GTF files using precomputed tracks or computes and scores multiple sequence alignments on the fly with MMseqs2.AvailabilityPhyloCSF++ is released under the AGPLv3 license. Binaries and source code are available athttps://github.com/cpockrandt/PhyloCSFpp. The software can be installed through bioconda. A variety of tracks can be accessed throughftp://ftp.ccb.jhu.edu/pub/software/phylocsfpp/.Contactpockrandt@jhu.edu,martin.steinegger@snu.ac.kr
Tight junction ZO proteins maintain tissue fluidity, ensuring efficient collective cell migration
Authors: Skamrahl Mark , Pang Hongtao , Ferle Maximilian , Gottwald Jannis , Rübeling Angela , Maraspini Riccardo , Honigmann Alf , Oswald Tabea A. , Janshoff Andreas 
Published: March 2021

AbstractTight junctions are essential components of epithelial tissues connecting neighboring cells to provide protective barriers. Albeit their general function to seal compartments is well understood, their role in collective cell migration is largely unexplored. Here, the importance of the tight junction proteins ZO1 and ZO2 for epithelial migration is investigated employing video microscopy in conjunction with velocimetry, segmentation, cell tracking, and atomic force microscopy/spectroscopy. The results indicate that ZO proteins are necessary for fast and coherent migration. In particular, ZO1 and 2 loss (dKD) induces actomyosin remodeling away from the central cortex towards the periphery of individual cells, resulting in altered viscoelastic properties. A tug-of-war emerges between two subpopulations of cells with distinct morphological and mechanical properties: 1) smaller and highly contractile cells with an outward-bulged apical membrane, and 2) larger, flattened cells, which, due to tensile stress, display a higher proliferation rate. In response, the cell density increases, leading to crowding-induced jamming and more small cells over time. Co-cultures comprising wildtype and dKD cells display phase separation based on differences in contractility rather than differential adhesion. This study shows that ZO proteins are necessary for efficient collective cell migration by maintaining tissue fluidity and controlling proliferation.
Lamb1a regulates atrial growth by limiting excessive, contractility-dependent second heart field addition during zebrafish heart development
Authors: Derrick Christopher J. , Pollitt Eric J. G. , Uruchurtu Ashley Sanchez Sevilla , Hussein Farah , Noёl Emily S. 
Published: March 2021

AbstractDuring early vertebrate heart development, the heart transitions from a linear tube to a complex asymmetric structure. This process includes looping of the tube and ballooning of the emerging cardiac chambers, which occur simultaneously with growth of the heart. A key driver of cardiac growth is deployment of cells from the Second Heart Field (SHF) into both poles of the heart, with cardiac morphogenesis and growth intimately linked in heart development. Laminin is a core component of extracellular matrix (ECM) basement membranes, and although mutations in specific laminin subunits are linked with a variety of cardiac abnormalities, including congenital heart disease and dilated cardiomyopathy, no role for laminin has been identified in early vertebrate heart morphogenesis. We identified dynamic, tissue-specific expression of laminin subunit genes in the developing zebrafish heart, supporting a role for laminins in heart morphogenesis.lamb1amutants exhibit cardiomegaly from 2dpf onwards, with subsequent progressive defects in cardiac morphogenesis characterised by a failure of the chambers to compact around the developing atrioventricular canal. We show that loss oflamb1aresults in excess addition of SHF cells to the atrium, revealing that Lamb1a functions to limit heart size during cardiac development by restricting SHF addition to the venous pole.lamb1amutants exhibit hallmarks of altered haemodynamics, and specifically blocking cardiac contractility inlamb1amutants rescues heart size and atrial SHF addition. Furthermore, we identify that FGF and RA signalling, two conserved pathways promoting SHF addition, are regulated by heart contractility and are dysregulated inlamb1amutants, suggesting that laminin mediates interactions between SHF deployment, heart biomechanics, and biochemical signalling during heart development. Together, this describes the first requirement for laminins in early vertebrate heart morphogenesis, reinforcing the importance of specialised ECM composition in cardiac development.
Shank3 influences mammalian sleep development
Authors: Medina Elizabeth , Schoch Hannah , Wintler Taylor , Ford Kaitlyn , Singletary Kristan G. , Peixoto Lucia 
Published: March 2021

ABSTRACTSleep problems are prevalent in Autism Spectrum Disorder (ASD), can be observed before diagnosis, and are associated with increased restricted and repetitive behaviors. Therefore, sleep abnormalities may be a core feature of the disorder, but the developmental trajectory remains unknown. Animal models provide a unique opportunity to understand sleep ontogenesis in ASD. Previously we showed that adult mice with a truncation in the high-confidence ASD geneShank3(Shank3ΔC) recapitulate the clinical sleep phenotype. In this study we used longitudinal electro-encephalographic (EEG) recordings to define, for the first time, changes in sleep from weaning to young adulthood in an ASD mouse model. We show that Shank3ΔCmice sleep less overall throughout their lifespan, have increased rapid eye movement (REM) sleep early in life despite significantly reduced non-rapid eye movement (NREM) sleep, and have abnormal responses to increased sleep pressure that emerge during a specific developmental period. We demonstrate that the ability to fall asleep quickly in response to sleep loss develops normally between 24 and 30 days in mice. However, mutants are unable to reduce sleep latency after periods of prolonged waking and maintain the same response to sleep loss regardless of age. This phenomenon seems independent of homeostatic NREM sleep slow-wave dynamics. Overall, our study recapitulates both preclinical models and clinical studies showing that reduced sleep is consistently associated with ASD and suggests that problems falling asleep may reflect abnormal development of sleep and arousal mechanisms.SIGNIFICANCE STATEMENTIn this first longitudinal sleep study in an Autism mouse model, we demonstrate that sleeping less seems a core feature of the disorder while problems falling asleep emerge during development.
A photoswitchable helical peptide with light-controllable interface / transmembrane topology in lipidic membranes
Authors: Gutiérrez-Salazar Mónica , Santamaría-Aranda Eduardo , Schaar Louise , Salgado Jesús , Sampedro Diego , Lorenz-Fonfria Victor A. 
Published: March 2021

AbstractAccording to the three-step model, the spontaneous insertion and folding of helical transmembrane (TM) polypeptides into lipid bilayers is driven by three sequential equilibria: solution-to-membrane interface (MI) partition, unstructured-to-helical folding, and MI-to-TM helix insertion. However, understanding these three steps with molecular detail has been challenged by the lack of suitable experimental approaches to rapidly and reversibly perturb membrane-bound hydrophobic polypeptides out of equilibrium. Here, we report on a 24-residues-long hydrophobic α-helical polypeptide, covalently coupled to an azobenzene photoswitch (KCALP-azo), which displays a light-controllable TM/MI equilibrium in hydrated lipid bilayers. FTIR spectroscopy shows that dark-adapted KCALP-azo (transazobenzene) folds as a TM α-helix, with its central TM region displaying an average tilt of 36 ± 4° with the membrane normal (TM topology). Aftertrans-to-cisphotoisomerization of the azobenzene moiety with UV light (reversed with blue light), spectral changes by FTIR spectroscopy indicate that the helical structure of KCALP-azo is maintained but the peptide experiences a more polar environment. Interestingly, pH changes induced similar spectral alterations in the helical peptide LAH4, with a well-characterized pH-dependent TM/MI equilibrium. Polarized experiments confirmed that the membrane topology of KCALP-azo is altered by light, with its helix tilt changing reversibly from 32 ± 5° (TM topology, blue light) to 79 ± 8° (MI topology, UV light). Further analysis indicates that, while thetransisomer of KCALP-azo is ~100% TM, thecisisomer exists in a ~90% TM and ~10% MI mixture. Strategies to further increase the perturbation of the TM/MI equilibrium with the light are briefly discussed.
Differential expression of H2A isoforms contribute to tissue and lineage specificity with HIST2H2AC as a potential cancer biomarker
Authors: Girish Shah Sanket , Rashid Mudasir , Natu Abhiram , Gupta Sanjay 
Published: March 2021

AbstractRecent advancements in the field of histone biology imply non-redundancy in the function of histone H2A isoforms; however, the expression of H2A isoforms in various normal tissue types, the correlation among organs and tumor/tumor type-specific expression remain poorly investigated. The profiling of sixteen H2A isoforms in eleven different normal human tissue types strongly suggests their tissue-specific or predominant expression. Further, clustering analysis shows a lineage-specific correlation of H2A isoforms. In continuation, the expression analysis in twelve human tumor types shows overexpression of HIST2H2AC. Moreover, overexpression was observed exclusively in tumor samples but not with fetal samples; highlighting the cancer-specific association of HIST2H2AC. Further,in silicoanalysis of TCGA pan-cancer data also showed tumor-specific over-expression of the HIST2H2AC isoform. Our findings provide insights into tissue-type-specificity of histone H2A isoforms expression patterns and advance our understanding of their importance in lineage specification and cancer.
Neural Basis of the Delayed Gratification
Authors: Gao Zilong , Wang Hanqing , Lu Chen , Froudist-Walsh Sean , Chen Ming , Wang Xiao-jing , Hu Ji , Sun Wenzhi 
Published: March 2021

AbstractBalancing instant gratification versus delayed, but better gratification is important for optimizing survival and reproductive success. Although psychologists and neuroscientists have long attempted to study delayed gratification through human psychological and brain activity monitoring, and animal research, little is known about its neural basis. We successfully trained mice to perform a waiting-and-water-reward delayed gratification task and used these animals in physiological recording and optical manipulation of neuronal activity during the task to explore its neural basis. Our results showed that the activity of DA neurons in ventral tegmental area (VTA) increases steadily during the waiting period. Optical activation vs. silencing of these neurons, respectively, extends or reduces the duration of waiting. To interpret this data, we developed a reinforcement learning (RL) model that reproduces our experimental observations. In this model, steady increases in DAergic activity signal the value of waiting and support the hypothesis that delayed gratification involves real-time deliberation.TEASERSustained ramping dopaminergic activation helps individuals to resist impulsivity and wait for laerger but later return.