bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuron Type-Specific Translatomes in Spinal Cords of Naïve and Neuropathic Mice
Authors: Das Gupta R.R. , Scheurer L. , Pelczar P. , Ralvenius W.T. , Wildner H. , Zeilhofer H.U. 
Published: March 2020

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, the molecular identity of the underlying neurons and signaling mechanisms are still only partially understood. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (VGLUT2+) and inhibitory GABA and/or glycinergic (VGAT+or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are primarily set apart by the expression of genes encoding transcription factors or genes related to the production, release or re-uptake of their principal neurotransmitters (glutamate, GABA or glycine). Subsequent gene ontology (GO) term analyses revealed that neuropeptide signaling-related GO terms were highly enriched in the excitatory population. Eleven neuropeptide genes displayed largely non-overlapping expression patterns closely adhering to the laminar and hence also functional organization of the spinal cord grey matter, suggesting that they may serve as major determinants of modality-specific processing. Since this modality-specific processing of sensory input is severely compromised in chronic, especially neuropathic, pain, we also investigated whether peripheral nerve damage changes the neuron typespecific translatome. In summary, our results suggest that neuropeptides contribute to modalityspecific sensory processing in the spinal cord but also indicate that altered sensory encoding in neuropathic pain states occurs independent of major translatome changes in the spinal neurons.
CitrusKB: A Comprehensive Knowledge Base for Transcriptome and Interactome ofCitrusspp. Infected byXanthomonas citrisubsp.citriat Different Infection Stages
Authors: Ferrasa Adriano , Murata Mayara M. , Cofre Teresa D. C. G. , Cavallini Juliana S. , Peron Gustavo , Julião Maria H. M. , Belasque José , Ferreira Henrique , Ferro Maria Inês T. , Leite Rui P. , Penha Helen A. , Carvalho Flávia M. S. , Varani Alessandro M. , Herai Roberto H. , Ferro Jesus A. 
Published: March 2020

AbstractCitrus canker type A is a serious disease caused byXanthomonas citrisubsp.citri(X. citri), which is responsible for severe losses to growers and to the citrus industry worldwide. To date, no canker-resistant citrus genotypes are available, and there is limited information regarding the molecular and genetic mechanisms involved in the early stages of the citrus canker development. Here, we present the knowledge base for transcriptome ofin vivocitrus interactome, the CitrusKB. This is the firstin vivointeractome database for different citrus cultivars, and it was produced to provide a valuable source of information on citrus and their interaction with the citrus canker bacteriumX. citri. The database provides tools for a user-friendly web interface to search and analyze a large amount of information regarding eight citrus cultivars with distinct levels of susceptibility to the disease and their interaction, at different stages of infection, with the citrus canker bacteriumX. citri. Currently, CitrusKB comprises a reference citrus genome and its transcriptome, expressed transcripts, pseudogenes and predicted genomic variations (SNPs and SSRs). The updating process will continue by incorporating annotations and analysis tools. We expect that CitrusKB may substantially contribute to the area of citrus genomics. CitrusKB is accessible athttp://bioinfo.deinfo.uepg.br/citrus. Users can download all the generated raw sequences and generated datasets by this study from the CitrusKB website.
Exercise promotes satellite cell contribution to myofibers in a load-dependent manner
Authors: Masschelein Evi , D’Hulst Gommaar , Zvick Joel , Hinte Laura , Soro-Arnaiz Inés , Gorski Tatiane , von Meyenn Ferdinand , Bar-Nur Ori , De Bock Katrien 
Published: March 2020

AbstractSatellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown. By performing SC fate tracing experiments, we show that 8-weeks of voluntary wheel running increased SC contribution to myonuclei in mouse plantar flexor muscles in a load-dependent but fiber type-independent manner. Increased SC fusion however was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy. Due to nuclear propagation, nuclear fluorescent fate tracing mouse models were inadequate to quantify SC contribution to myonuclei. Ultimately, by performing fate tracing at the DNA level, we show that SC contribution mirrors myonuclear accretion during exercise. Collectively, these findings provide direct evidence that mechanical load during exercise independently promotes SC contribution to existing myofibers.
CDK8 fine-tunes IL-6 transcriptional activities by limiting STAT3 resident time at the gene loci
Authors: Martinez-Fabregas J. , Wang L. , Pohler E. , Cozzani A. , Kazemian M. , Mitra S. , Moraga I. 
Published: March 2020

ABSTRACTCytokines are highly pleiotropic ligands that critically contribute to a balanced immune response. We have an incomplete understanding of how cytokines elicit their functional pleiotropy, which has limited their therapeutic use. Here, using Interleukin-6 (IL-6) as a model system, we have performed detailed phosphoproteomic and transcriptomic studies in human Th-1 cells to address the molecular bases defining cytokine functional pleiotropy. We have identified CDK8 as a new negative regulator of STAT3 transcriptional activities that contributes to the diversification of IL-6 responses. We found that CDK8 is a major regulator of the IL-6 phosphoproteome and interacts with STAT3 in the nucleus upon IL-6 stimulation. Inhibition of CDK8 activity, using specific small molecules inhibitors, reduced the IL-6-induced phosphoproteome by 23% in Th-1 cells, including STAT3 Ser727 phosphorylation. This, in turn, resulted in retention of tyrosine phosphorylated STAT3 in the nucleus, which increased the binding of STAT3 to target DNA sites in the genome with a concomitant increase in STAT3 mediated transcriptional activity. Importantly, inhibition of CDK8 activity under Th-17 polarizing conditions resulted in an enhancement of Th-17 differentiation. Our results support a model where CDK8 regulates STAT3 transcriptional processivity via modulation of its gene loci resident time, critically contributing to tuning STAT3 mediated responses.
Kentrophoros magnussp. nov. (Ciliophora, Karyorelictea), a new flagship species of marine interstitial ciliates
Authors: Seah Brandon K. B. , Volland Jean-Marie , Leisch Nikolaus , Schwaha Thomas , Dubilier Nicole , Gruber-Vodicka Harald R. 
Published: March 2020

ABSTRACTThe karyorelictean ciliateKentrophoroslacks a defined oral apparatus but has a dense coat of symbiotic bacteria that it consumes by phagocytosis. Body size, shape, and nuclear characters are variable in this genus. We formally describe a new species,K. magnusfrom Elba (Italy), which has unusual folding of its symbiont-bearing surface into pouch-like compartments, a body form that we term “pseudotrophosomal”.K. magnuscells are large (2100 ± 700 × 170 ± 23 μm in vivo), but contain only one micronucleus and two macronuclei, although these are much bigger than otherKentrophoros(widths 20 ± 2.5 and 31 ± 4.0 μm respectively inK. magnus). We also present morphological observations on a close relative from Twin Cayes (Belize), which also has relatively large nuclei (micronuclei 13 ± 1.5 μm, mature macronuclei 20 ± 2.8 μm), but unlikeK. magnus, it has on average 22 nuclei per cell, with different developmental stages of the macronuclei present simultaneously, and lacks pouch-like folding. Nuclear number and arrangement are important characters for karyorelicts. We suggest the use of a “nuclear formula” to simplify descriptions. Our discovery of large and morphologically distinctive new species underlines the incompleteness of our knowledge about meiofaunal ciliates.
EFA6B regulates a stop signal for collective invasion in breast cancer
Authors: Racha Fayad , Monserrat Vázquez Rojas , Mariagrazia Partisani , Pascal Finetti , Shiraz Dib , Virginie Virolle , Olivier Cabaud , Marc Lopez , Daniel Birnbaum , François Bertucci , Michel Franco , Frédéric Luton 
Published: March 2020

AbstractCancer is initiated by somatic mutations in oncogenes or tumor suppressor genes, however additional mutations provide selective advantages to the tumor cells to resist treatment and develop metastases, therefore identification of secondary mutations is of paramount importance. EFA6B (Exchange Factor for ARF6, B) expression is reduced in breast cancer. To study the pro-tumoral impact of the loss of EFA6B we have invalidated its gene in normal human mammary cells. We found that EFA6B knock-out triggers a transcriptional reprogramming of the cell-to-ECM interaction machinery and unleashes CDC42-dependent collective invasion in collagen. In addition, invasive and metastatic tumors isolated from patients have lower expression of EFA6B and display gene ontology signatures identical to those of EFA6B knock-out cells. Thus, we reveal a new EFA6B-regulated molecular mechanism that controls the invasive potential of mammary cells; this finding opens up new avenues for the treatment of invasive breast cancer.
The histone variant H2A.W and linker histone H1 co-regulate heterochromatin accessibility and DNA methylation
Authors: Bourguet Pierre , Picard Colette L. , Yelagandula Ramesh , Pélissier Thierry , Lorković Zdravko J. , Feng Suhua , Pouch-Pélissier Marie-Noëlle , Schmücker Anna , Jacobsen Steven E. , Berger Frédéric , Mathieu Olivier 
Published: March 2020

AbstractIn flowering plants, heterochromatin is demarcated by the histone variant H2A.W, elevated levels of the linker histone H1, and specific epigenetic modifications, such as high levels of DNA methylation at both CG and non-CG sites. How H2A.W regulates heterochromatin organization and interacts with other heterochromatic features is unclear. To analyze thein vivofunction of H2A.W, we created ah2a.wnull mutant via CRISPR-Cas9,h2a.w-2.We find that H2A.W antagonizes deposition of H1 at heterochromatin and that non-CG methylation and accessibility are moderately decreased inh2a.w-2heterochromatin. Compared to H1 loss alone, combined loss of H1 and H2A.W greatly increases accessibility and facilitates non-CG DNA methylation in heterochromatin, suggesting co-regulation of heterochromatic features by H2A.W and H1. Our results suggest that H2A.W helps maintain optimal heterochromatin accessibility and DNA methylation by promoting chromatin compaction together with H1, while also inhibiting excessive H1 incorporation.
Mouth magnetoencephalography: A unique perspective on the human hippocampus
Authors: Tierney Tim M. , Levy Andrew , Barry Daniel N. , Meyer Sofie S. , Shigihara Yoshihito , Everatt Matt , Mellor Stephanie , Lopez Jose David , Bestmann Sven , Holmes Niall , Roberts Gillian , Hill Ryan M , Boto Elena , Leggett James , Shah Vishal , Brookes Matthew J. , Bowtell Richard , Maguire Eleanor A. , Barnes Gareth R. 
Published: March 2020

AbstractTraditional magnetoencephalographic (MEG) brain imaging scanners consist of a rigid sensor array surrounding the head; this means that they are maximally sensitive to superficial brain structures. New technology based on optical pumping means that we can now consider more flexible and creative sensor placement. Here we explored the magnetic fields generated by a model of the human hippocampus not only across scalp but also at the roof of the mouth. We found that simulated hippocampal sources gave rise to dipolar field patterns with one scalp surface field extremum at the temporal lobe and a corresponding maximum or minimum at the roof of the mouth. We then constructed a fitted dental mould to accommodate an Optically Pumped Magnetometer (OPM). We collected data using a previously validated hippocampal-dependent task to test the empirical utility of a mouth-based sensor, with an accompanying array of left and right temporal lobe OPMs. We found that the mouth sensor showed the greatest task-related theta power change. We also found that, as predicted by the simulations, the mouth sensor was anti-correlated with those on over the temporal lobes. We found that this sensor had a mild effect on the reconstructed power in the hippocampus (~10% change) but that coherence images between the mouth sensor and reconstructed source images showed a global maximum in the right hippocampus. We conclude that augmenting a scalp-based MEG array with sensors in the mouth shows unique promise for both basic scientists and clinicians interested in interrogating the hippocampus.
Zebrafish Ski7 tunes RNA levels during the oocyte-to-embryo transition
Authors: Cabrera Quio Luis Enrique , Schleiffer Alexander , Mechtler Karl , Pauli Andrea 
Published: March 2020

AbstractPost-transcriptional mechanisms are crucial for the regulation of gene expression. These mechanisms are particularly important during rapid developmental transitions such as the oocyte-to-embryo transition, which is characterized by dramatic changes to the developmental program in the absence of nuclear transcription. Under these conditions, changes to the RNA content are solely dependent on RNA degradation. Although several mechanisms that promote RNA decay during embryogenesis have been identified, it remains unclear which cellular machineries contribute to remodeling the maternal transcriptome during the oocyte-to-embryo transition. Here, we focused on the auxiliary 3’-to-5’ degradation factor Ski7 in zebrafish as its mRNA peaks during this time frame. Homozygousski7mutant fish were viable and developed into morphologically normal adults, yet they had decreased fertility. Consistent with the idea that Ski7 participates in remodeling the transcriptome during the oocyte-to-embryo transition, transcriptome profiling identified stage-specific mRNA targets of Ski7. Genes upregulated inski7mutants were generally lowly expressed in wild type, suggesting that Ski7 maintains low transcript levels for this subset of genes. GO enrichment analyses of genes mis-regulated inski7mutants implicated Ski7 in the regulation of redox processes. This was confirmed experimentally by an increased resistance ofski7mutant embryos to reductive stress. Overall, our results provide first insights into the physiological role of vertebrate Ski7 as an important post-transcriptional regulator during the oocyte-to-embryo transition.
Methylglyoxal induces nuclear accumulation of p53 and γH2AX in normal and cancer cells
Authors: Veß Astrid , Hollemann Thomas 
Published: March 2020

AbstractThe formation and accumulation of methylglyoxal (MGO) is associated with age-related diseases such as diabetes, cancer and neurodegenerative disorders. MGO is the major precursor of non-enzymatic glycation of macromolecules affecting their function and structure. We now show for the first time that MGO stress not only led to cellular aging responses like DNA double-strand breaks indicated by an accumulation of γH2AX in the nucleus. We also observed an immediate increase of Ser15 phosphorylated p53 in the nucleus of MGO treated cell lines which will change the cellular expression pattern with adverse effects on the cell cycle and other cellular functions not necessarily related to aging.
Cortical inactivation does not block response enhancement in the superior colliculus
Authors: Kordecka Katarzyna , Foik Andrzej T. , Wierzbicka Agnieszka , Waleszczyk Wioletta J. 
Published: March 2020

AbstractRepetitive visual stimulation is successfully used in a study on the visual evoked potential (VEP) plasticity in the visual system in mammals. Practicing visual tasks or repeated exposure to sensory stimuli can induce neuronal network changes in the cortical circuits and improve the perception of these stimuli. However little is known about the effect of visual training at the subcortical level. In the present study, we extend the knowledge showing positive results of this training in the rat’s superior colliculus (SC). In electrophysiological experiments, we showed that a single training session lasting several hours induces a response enhancement both in the primary visual cortex (V1) and in the SC. Further, we tested if collicular responses will be enhanced without V1 input. For this reason, we inactivated the V1 by applying xylocaine solution onto the cortical surface during visual training. Our results revealed that SC’s response enhancement was present even without V1 inputs and showed no difference in amplitude comparing to VEPs enhancement while the V1 was active. These data suggest that the visual system plasticity and facilitation can develop independently but simultaneously in different parts of the visual system.
Bar-seq strategies for the LeishGEdit toolbox
Authors: Beneke Tom , Gluenz Eva 
Published: March 2020

AbstractThe number of fully sequenced genomes increases steadily but the function of many genes remains unstudied. To accelerate dissection of gene function inLeishmaniaspp. and other kinetoplastids we developed previously a streamlined pipeline for CRISPR-Cas9 gene editing, which we termed LeishGEdit [1]. To facilitate high-throughput mutant screens we have adapted this pipeline by barcoding mutants with unique 17-nucleotide barcodes, allowing loss-of-function screens in mixed populations [2]. Here we present primer design and analysis tools that facilitate these bar-seq strategies. We have developed a standalone easy-to-use pipeline to design CRISPR primers suitable for the LeishGEdit toolbox for any given genome and have generated a list of 14,995 barcodes. Barcodes and oligos are now accessible through our websitewww.leishgedit.netallowing to pursue bar-seq experiments in all currently available TriTrypDB genomes (release 41). This will streamline CRISPR bar-seq assays in kinetoplastids, enabling pooled mutant screens across the community.HighlightsDeveloping tools for pooled bar-seq mutant screens across the kinetoplastid communityDevelopment of a standalone script to design primers suitable for the LeishGEdit toolboxGeneration of 14,995 barcodes that can be used for bar-seq strategies in kinetoplastidsBar-seq primers for all TriTrypDB genomes (release 41) can be obtained fromwww.leishgedit.net
SPHERE: A novel approach to 3D and active sound localization
Authors: Gaveau V. , Coudert A. , Salemme R. , Koun E. , Desoche C. , Truy E. , Farne A. , Pavani F. 
Published: March 2020

AbstractIn everyday life, localizing a sound source in free-field entails more than the sole extraction of monaural and binaural auditory cues to define its location in the three-dimensions (azimuth, elevation and distance). In spatial hearing, we also take into account all the available visual information (e.g., cues to sound position, cues to the structure of the environment), and we resolve perceptual ambiguities through active listening behavior, exploring the auditory environment with head or/and body movements. Here we introduce a novel approach to sound localization in 3D named SPHERE (European patent n° WO2017203028A1), which exploits a commercially available Virtual Reality Head-mounted display system with real-time kinematic tracking to combine all of these elements (controlled positioning of a real sound source and recording of participants’ responses in 3D, controlled visual stimulations and active listening behavior). We prove that SPHERE allows accurate sampling of the 3D spatial hearing abilities of normal hearing adults, and it allowed detecting and quantifying the contribution of active listening. Specifically, comparing static vs. free head-motion during sound emission we found an improvement of sound localization accuracy and precisions. By combining visual virtual reality, real-time kinematic tracking and real-sound delivery we have achieved a novel approach to the study of spatial hearing, with the potentials to capture real-life behaviors in laboratory conditions. Furthermore, our new approach also paves the way for clinical and industrial applications that will leverage the full potentials of active listening and multisensory stimulation intrinsic to the SPHERE approach for the purpose rehabilitation and product assessment.
Transposable elements resistant to epigenetic resetting in the human germline are epigenetic hotspots for development and disease
Authors: Dietmann Sabine , Keogh Michael J , Tang Walfred , Magnusdottir Erna , Kobayashi Toshihiro , Chinnery Patrick F , Surani M. Azim 
Published: March 2020

ABSTRACTDespite the extensive erasure of DNA methylation in the early human germline, nearly eight percent of CpGs are resistant to the epigenetic resetting in the acutely hypomethylated primordial germ cells (week 7-9 hPGCs). Whether this occurs stochastically or represents relatively conserved layer of epigenetic information is unclear. Here we show that several predominantly hominoid-specific families of transposable elements (TEs) consistently resist DNA demethylation (henceforth called hPGC-methylated TEs or ‘escapees’) during the epigenetic resetting of hPGCs. Some of them undergo subsequent dynamic epigenetic changes during embryonic development. Our analysis of the fetal cerebral cortex also revealed multiple classes of young hPGC-methylated TEs within putative and established enhancers. Remarkably, specific hPGC-methylated TE subfamilies were associated with a multitude of adaptive human traits, including hair color and intelligence, and diseases including schizophrenia and Alzheimer’s disease. We postulate that hPGC-methylated TEs represent potentially heritable information within the germline with a role in human development and evolution.
DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain
Authors: Zhang Jing , Bellani Marina A. , James Ryan , Pokharel Durga , Zhang Yongqing , Reynolds John J. , McNee Gavin S. , Jackson Andrew P. , Stewart Grant S. , Seidman Michael M. 
Published: March 2020

AbstractDuplication of mammalian genomes requires replisomes to overcome numerous impediments during passage through open (eu) and condensed (hetero) chromatin. Typically, studies of replication stress characterize mixed populations of challenged and unchallenged replication forks, averaged across S phase, and model a single species of “stressed” replisome. However, in cells containing potent obstacles to replication, we find two different lesion proximal replisomes. One is bound by the DONSON protein and is more frequent in early S phase, in regions marked by euchromatin. The other interacts with the FANCM DNA translocase, is more prominent in late S phase, and favors heterochromatin. The two forms can also be detected in unstressed cells. CHIP-seq of DNA associated with DONSON or FANCM confirms the bias of the former towards regions that replicate early and the skew of the latter towards regions that replicate late.