bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continual inactivation of genes involved in stem cell functional identity stabilizes progenitor commitment
Authors: Rives-Quinto Noemi , Komori Hideyuki , Janssens Derek H. , Kondo Shu , Dai Qi , Moore Adrian W. , Lee Cheng-Yu 
Published: February 2020

SummaryExpansion of the pool of stem cells that indirectly generate differentiated cells through intermediate progenitors drives vertebrate brain evolution. Due to a lack of lineage information, mechanistic investigation of the competency of stem cells to generate intermediate progenitors remains impossible. Fly larval brain neuroblasts provide excellentin vivomodels for investigating the regulation of stem cell functionality during neurogenesis. Type II neuroblasts undergo indirect neurogenesis by dividing asymmetrically to generate a neuroblast and a progeny that commits to an intermediate progenitor (INP) identity. We identified Tailless (Tll) as the master regulator that maintains type II neuroblast functional identity, including the competency to generate INPs. Successive inactivation during INP commitment inhibitstllactivation by Notch, preventing INPs from reacquiring neuroblast functionality. We propose that the continual inactivation of neural stem cell functional identity genes by histone deacetylation allows intermediate progenitors to stably commit to generating diverse differentiated cells during indirect neurogenesis.
TheR2R3-MYBgene family in banana (Musa acuminata): genome-wide identification, classification and expression patterns
Authors: Pucker Boas , Pandey Ashutosh , Weisshaar Bernd , Stracke Ralf 
Published: February 2020

AbstractTheR2R3-MYBgenes comprise one of the largest transcription factor gene families in plants, playing regulatory roles in plant-specific developmental processes, defense responses and metabolite accumulation. To date MYB family genes have not yet been comprehensively identified in the major staple fruit crop banana. In this study, we present a comprehensive, genome-wide analysis of theMYBgenes fromMusa acuminataDH-Pahang (A genome). A total of 285R2R3-MYBgenes as well as genes encoding three other classes of MYB proteins containing multiple MYB repeats were identified and characterised with respect to structure and chromosomal organisation. Organ- and development-specific expression patterns were determined from RNA-seq data. For 280M. acuminata MYBgenes for which expression was found in at least one of the analysed samples, a variety of expression patterns were detected. TheM. acuminata R2R3-MYBgenes were functionally categorised, leading to the identification of seven clades containing onlyM. acuminataR2R3-MYBs. The encoded proteins may have specialised functions that were acquired or expanded inMusaduring genome evolution. This functional classification and expression analysis of theMYBgene family in banana establishes a solid foundation for future comprehensive functional analysis of MaMYBs and can be utilized in banana improvement programmes.
Survival strategies ofEnterococcus mundtiiin the gut ofSpodoptera littoralis: a live report
Authors: Mazumdar Tilottama , Teh Beng Soon , Murali Aishwarya , Schmidt-Heck Wolfgang , Schlenker Yvonne , Vogel Heiko , Boland Wilhelm 
Published: February 2020

AbstractThe complex interaction between a higher organism and its resident gut flora is a subject of immense interest in the field of symbiosis. Many insects harbor a complex community of microorganisms in their gut. Larvae ofSpodoptera littoralis, a lepidopteran pest which is prevalent in tropical and subtropical regions of the world, have a tube-like gut structure containing a simple bacterial community. This community varies both spatially (along the length of the gut) and temporally (during the life cycle of the insect).To monitor the dynamics and rapid adaptation of microbes to the gut conditions, a GFP-tagged reporterE. mundtiiwas constructed. After feeding to early instarS. littoralislarvae, the tagged-microbes recovered from the fore and hind guts by flow cytometry. The fluorescent reporter confirmed the persistence ofE. mundtiiin the gut. RNA-sequencing of the sorted bacteria highlighted various strategies that the symbiont employs to survive, including upregulated pathways for tolerating alkaline stress, forming biofilms and two-component signaling systems, resisting oxidative stress and quorum sensing. Although these symbionts depend on the host for amino acid and fatty acids, differential regulation among various metabolic pathways points to an enriched lysine synthesis pathway in the hindgut of the larvae.
Omnidirectional and omnifunctional connectivity analyses with a diverse species pool
Authors: Tessier Daphnée Lecours , Maranger Roxane , Poisot Timothée 
Published: February 2020

AbstractConnectivity among habitat patches in both natural and disturbed landscapes needs to be accounted for in conservation planning for biodiversity maintenance. Yet methods to assess connectivity are often limited, because simulating the dispersal of many species is computationally prohibitive, and current simulations make simplifying assumptions about movement that are potentially erroneous. Here we show how these limits can be circumvented and propose a novel framework for the assessment of omnifunctional and omnidirectional connectivity in a 28000 km2 area in the Laurentian region of Québec, Canada. Our approach relies on (i) the use ofOmniscape, an improved version ofCircuitscapewhich allows omnidirectional simulations that better emulate animal movement and (ii) the synthesis of large volume of species-level dispersal simulations througha posterioriclustering of the current intensity. Our analysis reveals that the movement of 93 species evaluated can be clustered into three functional dispersal guilds, corresponding to mostly aquatic species, terrestrial species able to use aquatic environments, and strictly terrestrial species. These functional guilds do not share connectivity hotspots, suggesting that corridor planning would need to account for the multiplicity of dispersal strategies. Although this approach requires a large volume of computing resources, it provides richer information on which landscape features are critical to maintain or need to be regenerated for broader biodiversity maintenance goals.
Toward an integrated classification of neuronal cell types: morphoelectric and transcriptomic characterization of individual GABAergic cortical neurons
Authors: Gouwens Nathan W. , Sorensen Staci A. , Baftizadeh Fahimeh , Budzillo Agata , Lee Brian R. , Jarsky Tim , Alfiler Lauren , Arkhipov Anton , Baker Katherine , Barkan Eliza , Berry Kyla , Bertagnolli Darren , Bickley Kris , Bomben Jasmine , Braun Thomas , Brouner Krissy , Casper Tamara , Crichton Kirsten , Daigle Tanya L. , Dalley Rachel , de Frates Rebecca , Dee Nick , Desta Tsega , Lee Samuel Dingman , Dotson Nadezhda , Egdorf Tom , Ellingwood Lauren , Enstrom Rachel , Esposito Luke , Farrell Colin , Feng David , Fong Olivia , Gala Rohan , Gamlin Clare , Gary Amanda , Glandon Alexandra , Goldy Jeff , Gorham Melissa , Graybuck Lucas , Gu Hong , Hadley Kristen , Hawrylycz Michael J. , Henry Alex M. , Hill DiJon , Hupp Madie , Kebede Sara , Kim Tae Kyung , Kim Lisa , Kroll Matthew , Lee Changkyu , Link Katherine E. , Mallory Matthew , Mann Rusty , Maxwell Michelle , McGraw Medea , McMillen Delissa , Mukora Alice , Ng Lindsay , Ng Lydia , Ngo Kiet , Nicovich Philip R. , Oldre Aaron , Park Daniel , Peng Hanchuan , Penn Osnat , Pham Thanh , Pom Alice , Potekhina Lydia , Rajanbabu Ramkumar , Ransford Shea , Reid David , Rimorin Christine , Robertson Miranda , Ronellenfitch Kara , Ruiz Augustin , Sandman David , Smith Kimberly , Sulc Josef , Sunkin Susan M. , Szafer Aaron , Tieu Michael , Torkelson Amy , Trinh Jessica , Tung Herman , Wakeman Wayne , Ward Katelyn , Williams Grace , Zhou Zhi , Ting Jonathan , Sumbul Uygar , Lein Ed , Koch Christof , Yao Zizhen , Tasic Bosiljka , Berg Jim , Murphy Gabe J. , Zeng Hongkui 
Published: February 2020

AbstractNeurons are frequently classified into distinct groups or cell types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 3,700 GABAergic mouse visual cortical neurons and reconstructed the local morphologies of 350 of those neurons. We found that most transcriptomic types (t-types) occupy specific laminar positions within mouse visual cortex, and many of those t-types exhibit consistent electrophysiological and morphological features. We observed that these properties could vary continuously between t-types, which limited the ability to predict specific t-types from other data modalities. Despite that, the data support the presence of at least 20 interneuron met-types that have congruent morphological, electrophysiological, and transcriptomic properties.HighlightsPatch-seq data obtained from>3,700 GABAergic cortical interneuronsComprehensive characterization of morpho-electric features of transcriptomic types20 interneuron met-types that have congruent properties across data modalitiesDifferent Sst met-types preferentially innervate different cortical layers
Epigenome-based Splicing Prediction using a Recurrent Neural Network
Authors: Lee Donghoon , Zhang Jing , Liu Jason , Gerstein Mark B 
Published: February 2020

AbstractAlternative RNA splicing provides an important means to expand metazoan transcriptome diversity. Contrary to what was accepted previously, splicing is now thought to predominantly take place during transcription. Motivated by emerging data showing the physical proximity of the spliceosome to Pol II, we surveyed the effect of epigenetic context on co-transcriptional splicing. In particular, we observed that splicing factors were not necessarily enriched at exon junctions and that most epigenetic signatures had a distinctly asymmetric profile around known splice sites. Given this, we tried to build an interpretable model that mimics the physical layout of splicing regulation where the chromatin context progressively changes as the Pol II moves along the guide DNA. We used a recurrent-neural-network architecture to predict the inclusion of a spliced exon based on adjacent epigenetic signals, and we showed that distinct spatio-temporal features of these signals were key determinants of model outcome, in addition to the actual nucleotide sequence of the guide DNA strand. After the model had been trained and tested (with >80% precision-recall curve metric), we explored the derived weights of the latent factors, finding they highlight the importance of the asymmetric time-direction of chromatin context during transcription.Author SummaryIn humans, only about 2% of the genome is comprised of so-called coding regions and can give rise to protein products. However, the human transcriptome is much more diverse than the number of genes found in these coding regions. Each gene can give rise to multiple transcripts through a process during transcription called alternative splicing. There is a limited understanding of the regulation of splicing and the underlying splicing code that determines cell-type-specific splicing. Here, we studied epigenetic features that characterize splicing regulation in humans using a recurrent neural network model. Unlike feedforward neural networks, this method contains an internal memory state that learns from spatiotemporal patterns – like the context in language – from a sequence of genomic and epigenetic information, making it better suited for characterizing splicing. We demonstrated that our method improves the prediction of spicing outcomes compared to previous methods. Furthermore, we applied our method to 49 cell types in ENCODE to investigate splicing regulation and found that not only spatial but also temporal epigenomic context can influence splicing regulation during transcription.
Salinomycin inhibits epigenetic modulator EZH2 to enhance Death Receptors in Colon Cancer Stem Cells
Authors: Singh Anup Kumar , Verma Ayushi , Singh Akhilesh , Arya Rakesh Kumar , Maheshwari Shrankhla , Chaturvedi Priyank , Nengroo Mushtaq Ahmad , Saini Krishan Kumar , Vishwakarma Achchhe Lal , Singh Kavita , Sarkar Jayanta , Datta Dipak 
Published: February 2020

AbstractDrug resistance is one of the trademark features of Cancer Stem Cells (CSCs). We and others have recently shown that paucity of functional death receptors (DR4/5) on the cell surface of tumor cells is one of the major reasons for drug resistance, but their involvement in the context of in CSCs is poorly understood. By harnessing CSC specific cytotoxic function of salinomycin, we discovered a critical role of epigenetic modulator EZH2 in regulating the expression of DRs in colon CSCs. Our unbiased proteome profiler array approach followed by ChIP analysis of salinomycin treated cells indicated that the expression of DRs, especially DR4 is epigenetically repressed in colon CSCs. Concurrently, EZH2 knockdown demonstrated increased expression of DR4/DR5, significant reduction of CSC phenotype such as spheroid formationin-vitroand tumorigenic potentialin-vivoin colon cancer. TCGA data analysis of human colon cancer clinical samples shows strong inverse correlation between EZH2 and DR4. Taken together, this study provides an insight about epigenetic regulation of DR4 in colon CSCs and advocates that drug resistant colon cancer can be therapeutically targeted by combining TRAIL and small molecule EZH2 inhibitors.
Optically Activated, Customizable, Excitable Cells - A Kuhl Platform for Evolving Next Gen Biosensors
Authors: Thomas Merrilee , Hughes Thom 
Published: February 2020

AbstractGenetically encoded fluorescent biosensors are powerful tools for studying complex signaling in the nervous system, and now both Ca2+and voltage sensors are available to study the signaling behavior of entire neural circuits. There is a pressing need for improved sensors to properly interrogate these systems. Improving them is challenging because testing them involves low throughput, labor-intensive processes. Our goal was to create a live cell system in HEK293 cells that use a simple, reproducible, optogenetic process for testing prototypes of genetically encoded biosensors.In this live cell system, blue light activates an adenylyl cyclase enzyme (bPAC) that increases intracellular cAMP [1]. In turn, the cAMP opens a cAMP gated ion channel (olfactory cyclic nucleotide-gated channel, CNG, or the hyperpolarization-activated cyclic nucleotide-gated channel, HCN2). This produces slow, whole-cell Ca2+transients and voltage changes. To increase the speed of these transients, we added the inwardly rectifying potassium channel Kir2.1, the bacterial voltage-gated sodium channel NAVROSD, and Connexin-43. This is a modular system in which the types of channels, and their relative amounts, can be tuned to produce the cellular behavior that is crucial for screening biosensors. The result is a highly reproducible, high-throughput live cell system that can be used to screen voltage and Ca2+sensors in multiple fluorescent wavelengths simultaneously.
Preservation and changes in oscillatory dynamics across the cortical hierarchy
Authors: Lundqvist Mikael , Bastos André M. , Miller Earl K. 
Published: February 2020

AbstractTheta (2-8 Hz), Alpha (8-12 Hz), beta (12-35 Hz) and gamma (>35 Hz) rhythms are ubiquitous in cortex. But there is little understanding of whether they have similar properties and functions in different cortical areas because they have rarely been compared across them. We record neuronal spikes and local field potentials simultaneously at several levels of the cortical hierarchy in monkeys. Theta, alpha, beta and gamma oscillations had similar relationships to spiking activity in visual, parietal and prefrontal cortex. However, the frequencies in all bands increased up the cortical hierarchy. These results suggest that these rhythms have similar functions inhibitory and excitatory across cortex. We discuss how the increase in frequencies up the cortical hierachy may help sculpt cortical flow and processing.Significance statementPhase-coupling in alpha/beta and gamma frequency ranges between cortical areas is often viewed as a means to shape brain-wide communication. However, systematic frequency differences between communicating areas are typically not considered, but equally important. Here we show that alpha/beta and gamma oscillations are of systematically higher frequency ascending the cortical hierarchy. This presents a fresh view on a widely studied topic. It has important implications in shaping cortical communication and helps explain widely observed phenomena.
Differentiating Drosophila female germ cells initiate Polycomb silencing by altering PRC2 sampling
Authors: DeLuca Steven Z , Ghildiyal Megha , Niu Wanbao , Pang Liang-Yu , Spradling Allan C. 
Published: February 2020

SummaryPolycomb silencing represses gene expression and provides a molecular memory of chromatin state that is essential for animal development. We show thatDrosophilafemale germline stem cells (GSCs) provide a powerful system for studying Polycomb silencing and how it is established. GSCs resemble pluripotent mammalian embryonic cells in lacking silenced chromatin, but most GSC daughters, like typical somatic cells, induce Polycomb silencing as they differentiate into nurse cells. Developmentally controlled changes in the levels of two Polycomb repressive complex 2 (PRC2)-interacting proteins, Pcl and Scm, initiate differentiation. In germline stem cells, abundant Pcl inhibits silencing by slowing PRC2 and diverting it from PRE sequences. During differentiation, core PRC2 represses inactive loci while Scm and residual Pcl cooperate to enrich PRC2 and silence traditional Polycomb domains. We propose that PRC2-interacting proteins regulate the transition from a variable to stable transcription state during differentiation by altering the rate that PRC2 samples regulatory sequences.
Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma
Authors: de Vargas Pinheiro Kelly , Thomaz Amanda , Souza Bárbara Kunzler , Metcalfe Victoria Anne , Freire Natália Hogetop , Brunetto André Tesainer , de Farias Caroline Brunetto , Jaeger Mariane , Bambini Victorio , Smith Christopher G.S. , Shaw Lisa , Roesler Rafael 
Published: February 2020

AbstractBackgroundA member of the Trk family of neurotrophin receptors, tropomyosin receptor kinase B (TrkB, encoded by theNTRK2gene) is an increasingly important target in various cancer types, including glioblastoma (GBM).EGFRis among the most frequently altered oncogenes in GBM, and EGFR inhibition has been tested as an experimental therapy. Functional interactions between EGFR and TrkB have been demonstrated. In the present study, we investigated the role of TrkB and EGFR, and their interactions, in GBM.Methods and ResultsAnalyses ofNTRK2andEGFRgene expression from The Cancer Genome Atlas (TCGA) datasets showed an increase inNTRK2expression in the proneural subtype of GBM, and a strong correlation betweenNTRK2andEGFRexpression in glioma CpG island methylator phenotype (G-CIMP+) samples. We showed that when TrkB and EGFR inhibitors were combined, the inhibitory effect on A172 human GBM cells was more pronounced than when either inhibitor was given alone. When U87MG GBM cells were xenografted into the flank of nude mice, tumor growth was delayed by treatment with TrkB and EGFR inhibitors, given alone or combined, only at specific time points. Intracranial GBM growth in mice was not significantly affected by drug treatments.ConclusionsOur findings indicate that correlations betweenNTRK2andEGFRexpression occur in specific GBM subgroups. Also, our results using cultured cells suggest for the first time the potential of combining TrkB and EGFR inhibition for the treatment of GBM.
Oncoprotein 18 is necessary for malignant cell proliferation in bladder cancer cells and serves as a G3-specific non-invasive diagnostic marker candidate in urinary RNA
Authors: Hanke Merle , Dubois Josephine , Kausch Ingo , Petkovic Sonja , Sczakiel Georg 
Published: February 2020

ABSTRACTBackgroundUrine-based diagnostics indicated involvement of OP18 in bladder cancer. In cell culture models we investigated the role of oncoprotein 18 for malignant cell growth.MethodsWe analyzed 113 urine samples and investigated two human BCa cell lines as a dual model: RT-4 and ECV-304, which represented differentiated (G1) and poorly differentiated (G3) BCa. We designed specific siRNA for down-regulation of OP18 in both cell lines. Phenotypes were characterized by cell viability, proliferation, and expression of apoptosis-related genes. Besides, sensitivity to cisplatin treatment was evaluated.ResultsAnalysis of urine samples from patients with urothelial BCa revealed a significant correlation of the RNA-ratio oncoprotein 18:uroplakin 1A with bladder cancer. High urinary ratios were mainly found in moderately to poorly differentiated tumors (grade G2-3) that were muscle invasive (stage T2-3), whereas samples from patients with more differentiated non-invasive BCa (G1) showed low OP18:UPK1A RNA ratios. Down-regulation of OP18 expression in ECV-304 shifted its phenotype towards G1 state. Further, OP18-directed siRNA induced apoptosis and increased chemo-sensitivity to cisplatin.ConclusionsThis study provides conclusive experimental evidence for the link between OP18-derived RNA as a diagnostic marker for molecular staging of BCa in non-invasive urine-based diagnostics and the patho-mechanistic role of OP18 suggesting this gene as a therapeutic target.
Genomic analyses reveal the origin of domestic ducks and identify different genetic underpinnings of wild ducks
Authors: Liu Rui , Liu Weiqing , Rong Enguang , Lu Lizhi , Li Huifang , Chen Li , Zhao Yong , Cao Huabin , Liu Wenjie , Chen Chunhai , Fan Guangyi , Song Weitao , Lu Huifang , Sun Yingshuai , Chen Wenbin , Liu Xin , Xu Xun , Li Ning 
Published: February 2020

AbstractDomestic ducks are considered to have been tamed from the mallard or a descendant of the mallard and the spot-billed duck. Domestic ducks show remarkable phenotypic variation in morphology, physiology and behaviour. However, the molecular genetics of the origin and phenotypic variation of ducks are still poorly studied.Here, we present mallard and spot-billed genomes and perform whole-genome sequencing on eight domestic duck breeds and eight wild duck species. Surprisingly, analyses of these data support a model in which domestic ducks diverged from their closest wild lineage (mallard ducks and spot-billed ducks) at the last glacial period (LGP, 100-300 kilo years ago (Kyr)). The wild lineage further speciated into mallard ducks and spot-billed ducks approximately 70 Kyr, whereas the domestic lineage population decreased through the LGP. A scan of wild duck genomes compared with domestic duck genomes identified numerous loci that may have been affected by positive selection in ancestral wild ducks after their divergence from domestic lineages. Function analyses suggested that genes usually affecting organ development and energy metabolism may involve long-distance flight ability. Further selective sweep analyses identified two genes associated with egg production and three genes related to feeding modulation under selection in domestic ducks. These analyses unravel a distinct evolutionary pattern of ducks and two wild duckde novogenomes, thus providing a novel resource for speciation studies.