bluuebunny/crossref_metadata_2025_split huggingface dataset:
It is Never as Good the Second Time Around: Brain Areas Involved in Salience Processing Habituate During Repeated Drug Cue Exposure in Methamphetamine and Opioid Users
Authors: Ekhtiari Hamed , Kuplicki Rayus , Aupperle Robin P , Paulus Martin P. 
Published: April 2020

AbstractIntroductionThe brain response to drug-related cues is an important marker in addiction-medicine, however, the temporal dynamics of this response in repeated exposure to the cues are not well known yet. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations.MethodsSixty-five male participants (35.8±8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD and 22 male with opioid use disorder). The second replication-sample was re-tested within two weeks.ResultsIn the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both significant condition and condition-by-time interaction with a habituation response for the drug-related cues but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed consistent lack of drug>neutral and habituation response within all selected clusters in the second cue-exposure session.ConclusionsVMPFC, amygdala and ventral striatum show a habituation in response to drug-related cues which is consistent among different clinical populations. Habituation in response in the first session of cue-exposure and lack of reactivity in the second session of exposure provide foundations for development of cue-desensitization interventions.
Identification of molecular specificity between reprogrammed cardiomyocytes and normal cardiomyocytes by bioinformatics
Authors: Liu Mengyao , Zhang yue 
Published: April 2020

AbstractThe adult human heart lacks an effective endogenous repair mechanism and cannot fully restore heart function after injury. We obtained two microarray data sets GSE99814 and GSE22292 from the NCBI GEO database, which include 5 groups of directly reprogrammed cardiomyocyte-like cells (iCMs) and 5 groups of normal mouse cardiomyocytes (CM). And through the GEO2R tool and Venn diagram software to screen the differentially expressed genes (DEG) between iCM and CM. Next, we performed functional enrichment analysis on these DEGs. The protein-protein interaction network (PPI) was constructed by STRING and Cytoscape for module analysis. We have selected a total of 243 DEGs consistently expressed genes in the two data sets, of which 127 up-regulated genes function and pathway enrichment mainly concentrated on biological processes such as innate immune response, inflammatory response, immune system process, positive regulation of apoptosis process and complement and coagulation cascade, while the 116 down-regulated genes are mainly enriched in cell cycle, cell division, cardiac development, myocardial contraction and myocardial cell development and signaling pathways such as cell cycle and adrenergic signaling in cardiomyocytes. Then in the PPI network, we found 27 central genes when analyzing these 243 DEGs by the Molecular Complex Detection (MCODE) plug-in. Finally, we reanalyzed these 27 central genes through DAVID and found that 6 genes (CCNB1, CCNB2, BUB1, TTK, CDC25C, CCNA2) significantly enriched the cell cycle signaling pathway (p<1.20E-07). Therefore, through integrated bioinformatics methods, we found that compary with iCMs and CMs, iCMs were induced by direct reprogramming of neonatal mouse cardiomyocytes, the DEGs were mainly enriched in immune-related processes and myocardial contraction and cell cycle signaling pathways (p< 0.05).
Comprehensive Chromosome End Remodeling During Programmed DNA Elimination
Authors: Wang Jianbin , Veronezi Giovana M.B. , Kang Yuanyuan , Zagoskin Maxim , O’Toole Eileen T. , Davis Richard E. 
Published: April 2020

AbstractGermline and somatic genomes are typically the same in a multicellular organism. However, in some organisms including the parasitic nematodeAscaris, programmed DNA elimination leads to a reduced somatic genome compared to germline cells. Previous work on the parasitic nematodeAscarisdemonstrated that programmed DNA elimination encompasses high fidelity chromosomal breaks at specific genome locations and loss of specific genome sequences including a major tandem repeat of 120 bp and ~1,000 germline-expressed genes. However, the precise chromosomal locations of the 120 bp repeats, the breaks regions, and the eliminated genes remained unknown. Here, we used PacBio long-read sequencing and chromosome conformation capture (Hi-C) to obtain fully assembled chromosomes ofAscarisgermline and somatic genomes, enabling a complete chromosomal view of DNA elimination. Surprisingly, we found that all 24 germline chromosomes undergo comprehensive chromosome end remodeling with DNA breaks in their subtelomeric regions and loss of distal sequences including the telomeres at both chromosome ends. All newAscarissomatic chromosome ends are recapped byde novotelomere healing. We provide an ultrastructural analysis of DNA elimination and show thatAscariseliminated DNA is incorporated into many double membrane-bound structures, similar to micronuclei, during telophase of a DNA elimination mitosis. These micronuclei undergo dynamic changes including loss of active histone marks and localize to the cytoplasm following daughter nuclei formation and cytokinesis where they form autophagosomes. Comparative analysis of nematode chromosomes suggests that germline chromosome fusions occurred formingAscarissex chromosomes that become independent chromosomes following DNA elimination breaks in somatic cells. These studies provide the first chromosomal view and define novel features and functions of metazoan programmed DNA elimination.
Mass Spectrometric Identification of SARS-CoV-2 Proteins from Gargle Solution Samples of COVID-19 Patients
Authors: Ihling Christian , Tänzler Dirk , Hagemann Sven , Kehlen Astrid , Hüttelmaier Stefan , Sinz Andrea 
Published: April 2020

AbstractMass spectrometry (MS) can deliver valuable diagnostic data that complements genomic information and allows us to increase our current knowledge of the COVID-19 disease caused by the SARS-CoV-2 virus. We developed a simple, MS-based method to specifically detect SARS-CoV-2 proteins from gargle solution samples of COVID-19 patients. Our protocol consists of an acetone precipitation and tryptic digestion of proteins contained within the gargle solution, followed by a targeted MS analysis. Our methodology identifies unique peptides originating from SARS-CoV-2 nucleoprotein. Building on these promising initial results, faster MS protocols can now be developed as routine diagnostic tools for COVID-19 patients.Graphical AbstractImage credit (left): Gerd Altmann, Pixabay License,https://pixabay.com/illustrations/corona-coronavirus-virus-covid-19-4959447
A Timescale for the Radiation of Photosynthetic Eukaryotes
Authors: Evanovich Eliane , de Souza Mendonça-Mattos Patricia Jeanne , Guerreiro João Farias 
Published: April 2020

AbstractOxygenic photosynthesis is considered the most important evolutionary innovation in the history of Earth. It depends on two photosystems, responsible for the photolysis of water and the reduction of carbon dioxide. Oxygen and carbohydrates are released at the end of the reaction. Extraordinary, the oxygen released created the stratospheric ozone layer, and transformed the ocean chemistry, whereas the carbohydrates are the primary source of energy for complex cells. Several lines of evidence indicate the photosynthesis arose in the ancestors of cyanobacteria. It was spread over some eukaryotes by the acquisition of a free-living cyanobacterium, which evolved into photosynthetic plastid, the chloroplast. The timing of the chloroplast emergence is still controversy. Estimated ages range from 600 to 2100 million years ago (Mya) in accordance to previous studies. The aim of this study is to clarify several aspects of the origin and diversification of photosynthetic eukaryotes. For this purpose, we utilized a data set based on 27 protein-coding genes from genomes of cyanobacteria and photosynthetic eukaryotes, more genes than other papers that also utilized plastid genes, and performed the Bayesian analysis method to estimate the divergence times of the photosynthetic eukaryotes. Results showed photosynthetic eukaryotes emerged Late Mesoproterozoic about 1342 Mya. The Early Proterozoic oceans did not have adequate conditions for eukaryotes, because chemical elements such as zinc and molybdenum were at reduced concentrations, and they are essential to the formation of eukaryotic proteins.
Neurophysiological indices of audiovisual speech integration are enhanced at the phonetic level for speech in noise
Authors: O’Sullivan Aisling E. , Crosse Michael J. , Di Liberto Giovanni M. , de Cheveigné Alain , Lalor Edmund C. 
Published: April 2020

AbstractSeeing a speaker’s face benefits speech comprehension, especially in challenging listening conditions. This perceptual benefit is thought to stem from the neural integration of visual and auditory speech at multiple stages of processing, whereby movement of a speaker’s face provides temporal cues to auditory cortex, and articulatory information from the speaker’s mouth can aid recognizing specific linguistic units (e.g., phonemes, syllables). However it remains unclear how the integration of these cues varies as a function of listening conditions. Here we sought to provide insight on these questions by examining EEG responses to natural audiovisual, audio, and visual speech in quiet and in noise. Specifically, we represented our speech stimuli in terms of their spectrograms and their phonetic features, and then quantified the strength of the encoding of those features in the EEG using canonical correlation analysis. The encoding of both spectrotemporal and phonetic features was shown to be more robust in audiovisual speech responses then what would have been expected from the summation of the audio and visual speech responses, consistent with the literature on multisensory integration. Furthermore, the strength of this multisensory enhancement was more pronounced at the level of phonetic processing for speech in noise relative to speech in quiet, indicating that listeners rely more on articulatory details from visual speech in challenging listening conditions. These findings support the notion that the integration of audio and visual speech is a flexible, multistage process that adapts to optimize comprehension based on the current listening conditions.Significance StatementDuring conversation, visual cues impact our perception of speech. Integration of auditory and visual speech is thought to occur at multiple stages of speech processing and vary flexibly depending on the listening conditions. Here we examine audiovisual integration at two stages of speech processing using the speech spectrogram and a phonetic representation, and test how audiovisual integration adapts to degraded listening conditions. We find significant integration at both of these stages regardless of listening conditions, and when the speech is noisy, we find enhanced integration at the phonetic stage of processing. These findings provide support for the multistage integration framework and demonstrate its flexibility in terms of a greater reliance on visual articulatory information in challenging listening conditions.
Concerted interactions between multiple gp41 trimers and the target cell lipidome may be required for HIV-1 entry
Authors: Gorai Biswajit , Sahoo Anil Kumar , Srivastava Anand , Dixit Narendra M. , Maiti Prabal K. 
Published: April 2020

ABSTRACTThe HIV-1 envelope glycoprotein gp41 mediates the fusion between viral and host cell membranes leading to virus entry and target cell infection. Despite years of research, important aspects of this process such as the number of gp41 trimers involved and how they orchestrate the rearrangement of the lipids in the apposed membranes along the fusion pathway remain obscure. To elucidate these molecular underpinnings, we performed coarse-grained molecular dynamics simulations of HIV-1 virions pinned to the CD4 T cell membrane by different numbers of gp41 trimers. We built realistic cell and viral membranes by mimicking their respective lipid compositions. We found that a single gp41 was inadequate for mediating fusion. Lipid mixing between membranes, indicating the onset of fusion, was efficient when 3 or more gp41 trimers pinned the membranes. The gp41 trimers interacted strongly with many different lipids in the host cell membrane, triggering lipid configurational rearrangements, exchange, and mixing. Simpler membranes, comprising fewer lipid types, displayed strong resistance to fusion, revealing the crucial role of the lipidomes in HIV-1 entry. Performing simulations at different temperatures, we estimated the free energy barrier to lipid mixing, and hence membrane stalk formation, with 4 tethering gp41 trimers to be ~6.2 kcal/mol, a >4-fold reduction over estimates without gp41. Together, these findings present molecular-level, quantitative insights into the early stages of gp41-mediated HIV-1 entry. Preventing the requisite gp41 molecules from tethering the membranes or altering membrane lipid compositions may be potential intervention strategies.SIGNIFICANCEInteractions between viral envelope proteins and host cell surface receptors leading to HIV-1 entry are well studied, however the role of membrane lipids remains obscure, although entry hinges on lipid mixing and the fusion of viral and cell membranes. We performed detailed simulations of HIV-1 and target cell membranes tethered by viral gp41 trimeric proteins to elucidate the proteo-lipidic contributions to viral entry. We found that the cooperative effects of multiple gp41 trimers and natural lipidomes of the membranes facilitate membrane fusion. The functional domains of gp41 altered local lipid concentrations, reduced membrane repulsions, and facilitated inter-membrane lipid mixing. These molecular-level insights offer a glimpse of the cryptic mechanisms underlying HIV-1 entry and suggest new interventions to combat HIV-1 infection.
Chronic Developmental Lead Exposure increases μ-Opiate Receptor Levels in the Adolescent Rat Brain
Authors: Albores-Garcia Damaris , McGlothan Jennifer L , Bursac Zoran , Guilarte Tomás R. 
Published: April 2020

AbstractOpioid use and abuse has reached epidemic proportion in the United States resulting in a significant numbers of deaths due to overdose. While environmental factors are implicated in opioid addiction, less is known about the role of exposure to environmental pollutants on the brain opioid system. Human and preclinical studies have suggested an association between childhood lead (Pb2+) intoxication and proclivity to substance abuse and delinquent behavior. Opioid receptors are involved in the biological effects of opioids and other drugs of abuse. In this study, we examine the effect of chronic developmental Pb2+exposure on μ-opioid receptor (MOR) levels in the rat brain using [3H]-D-Ala2-MePhe4-Gly-ol5 enkephalin ([3H]-DAMGO) quantitative receptor autoradiography.Our results indicate that chronic developmental Pb2+exposure increases the levels of [3H]-DAMGO specific binding to MOR in several limbic regions of the brain in male and female rats during the pre-adolescence (PN14) and early-adolescence (PN28) period. These changes were less pronounced in late-adolescence (PN50) and adult (PN120) animals. Our findings are important because the pre-adolescence and early adolescence period is a time in which there is higher engagement in reward and drug seeking behaviors in humans.In summary, we show that chronic exposure to Pb2+an ubiquitous and well-known environmental contaminant and neurotoxicant, alters MOR levels in brain regions associated with addiction circuits in the adolescent period with important implications to opioid drug use and abuse.
Rapid ‘multi-directed’ cholinergic transmission at central synapses
Authors: Sethuramanujam Santhosh , Matsumoto Akihiro , McIntosh J. Michael , Jing Miao , Li Yulong , Berson David , Yonehara Keisuke , Awatramani Gautam B. 
Published: April 2020

AbstractAcetylcholine (ACh) is a key neurotransmitter that plays diverse roles in many parts of the central nervous system, including the retina. However, assessing the precise spatiotemporal dynamics of ACh is technically challenging and whether ACh transmits signals via rapid, point-to-point synaptic mechanisms, or broader-scale ‘non-synaptic’ mechanisms has been difficult to ascertain. Here, we examined the properties of cholinergic transmission at individual contacts made between direction-selective starburst amacrine cells and downstream ganglion cells in the retina. Using a combination of electrophysiology, serial block-face electron microscopy, and two-photon ACh imaging, we demonstrate that ACh signaling bears the hallmarks of both non-synaptic and synaptic forms of transmission. ACh co-activates nicotinic ACh receptors located on the intersecting dendrites of pairs of ganglion cells, with equal efficiency (non-synaptic)— and yet retains the ability to generate rapid ‘miniature’ currents (∼1 ms rise times: synaptic). Fast cholinergic signals do not appear to depend on anatomically well-defined synaptic structures. We estimate that ACh spread is limited to ∼1-2µm from its sites of release, which may help starbursts drive local direction-selective cholinergic responses in ganglion cell dendrites. Together, our results establish the functional architecture for cholinergic signaling at a central synapse and propose a novel motif whereby single presynaptic sites can co-transmit information to multiple neurons on a millisecond timescale.
Quantitative partition of the rhizosphere microbiota assembly processes
Authors: Ling Ning , Xue Chao , Vandenkoornhuyse Philippe , Shen Qirong 
Published: April 2020

AbstractThe soil microbial reservoir and plant recruitment are predominant forces determining microbiota assembly in rhizosphere (i.e. active and passive processes respectively), but to date, no straightforward method to evaluate the respective contribution of forces to the rhizospheric microbiota assembly rules is available. We propose herein a promising way to quantitatively partition the assembling forces of rhizosphere microbiota using ordination metrics. We anticipate that this new method can not only weight the plants individual contributions to microbiota assembly in rhizosphere, but can also indirectly provide a way to quantitatively evaluate soil health by the contribution from plant selection.
Haploinsufficient tumour suppressor PRP4K is negatively regulated during epithelial-to-mesenchymal transition
Authors: Clarke Livia E. , Cook Allyson , Mathavarajah Sabateeshan , Bera Amit , Salsman Jayme , Habib Elias , Van Iderstine Carter , Bydoun Moamen , Lewis Stephen M. , Dellaire Graham 
Published: April 2020

ABSTRACTThe pre-mRNA processing factor 4 kinase (PRP4K, also known as PRPF4B) is an essential gene. However, reduced PRP4K expression is associated with aggressive breast and ovarian cancer phenotypes including taxane therapy resistance, increased cell migration and invasion in vitro and cancer metastasis in mice; results consistent with PRP4K being a haploinsufficient tumour suppressor. Increased cell migration and invasion is associated with epithelial-to-mesenchymal transition (EMT), but how reduced PRP4K levels affect normal epithelial cell migration or EMT has not been studied. Depletion of PRP4K by small hairpin RNA (shRNA) in non-transformed mammary epithelial cell lines (MCF10A, HMLE) reduced or had no effect on 2D migration in the scratch assay but resulted in greater invasive potential in 3D transwell assays. Depletion of PRP4K in mesenchymal triple negative breast cancer cells (MDA-MB-231) resulted in both enhanced 2D migration and 3D invasion, with 3D invasion correlated with higher fibronectin levels in both MDA-MB-231 and MCF10A cells and without changes in E-cadherin. Induction of EMT in MCF10A cells, by treatment with WNT-5a and TGF-β1, or depletion of eukaryotic translation initiation factor 3e (eIF3e) by shRNA, resulted in significantly reduced PRP4K expression. Mechanistically, induction of EMT by WNT-5a/TGF-β1 reduced PRP4K transcript levels, whereas eIF3e depletion led to reduced PRP4K translation. Finally, reduced PRP4K levels after eIF3e depletion correlated with increased YAP activity and nuclear localization, both of which are reversed by overexpression of exogenous PRP4K. Thus, PRP4K is a haploinsufficient tumour suppressor negatively regulated by EMT, that when depleted in normal mammary cells can increase cell invasion without inducing full EMT.
Endosomal spatio-temporal modulation of the cortical RhoA zone conditions epithelial cell organization
Authors: Cécile Gaston , Simon De Beco , Bryant Doss , Meng Pan , Estelle Gauquelin , Joseph D’Alessandro , Teck Lim Chwee , Benoit Ladoux , Delphine Delacour 
Published: April 2020

SummaryAt the basis of cell shape and behavior, actomyosin organization and force-generating property are widely studied, however very little is known about the regulation of the contractile network in space and time. Here we study the role of the epithelial-specific protein EpCAM, a contractility modulator, in cell shape and motility, and we show that it is required for the maturation of stress fibers and frontrear polarity acquisition at the single cell level. There, EpCAM ensures the remodeling of a transient active RhoA zone in the cortex of spreading epithelial cells. GTP-RhoA follows the endosomal pathway mediated by Rab35 and EHD1, where it co-evolves together with EpCAM. In fact, EpCAM balances GTP-RhoA turnover in order to tune actomyosin remodeling for cell shape, polarity and mechanical property acquisition. Impairment of GTP-RhoA endosomal trafficking either by EpCAM silencing or Rab35 / EHD1 mutant expression prevents correct myosin-II activity, stress fiber formation, and ultimately cell polarization. Collectively, this work shows that the coupling of EpCAM/RhoA co-trafficking to actomyosin rearrangement is critical for spreading, and advances our understanding of how biochemical and mechanical properties can be coupled for cell plasticity.
PROX1 transcription factor is a master regulator of myogenic and oncogenic features of rhabdomyosarcoma
Authors: Gizaw Nebeyu Yosef , Kallio Pauliina , Punger Tatjana , Kinnunen Matias , Gucciardo Erika , Lehti Kaisa , Haglund Caj , Böhling Tom , Varjosalo Markku , Sampo Mika , Alitalo Kari , Kivelä Riikka 
Published: April 2020

AbstractRhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue cancer in need for novel therapies. Here we show that the PROX1 transcription factor, which is essential for normal myoblast differentiation, is highly expressed in RMS tumors. We demonstrate that PROX1 is needed for RMS cell stemness and growthin vitro, and for RMS tumor formation in mouse xenograft models. In addition, we unveil that PROX1 is an essential for myogenic properties in RMS. PROX1 depletion reprogrammed the RMS transcriptome to resemble benign mesenchymal stem cells and repressed many of the previously identified RMS effector transcripts and myogenic genes. By using proximity labeling and mass spectrometry, we found that PROX1 interacts with the NuRD and CoREST complexes containing class I HDACs. Our studies reveal a major role of PROX1-HDAC interaction in RMS and give insights that inhibiting this interaction could be a promising therapeutic approach.