bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy
Authors: Shang Shenglan , Wu Jiaqi , Li Xiaoli , Liu Xin , Li Pan , Zheng Chunli , Wang Yonghua , Liu Songqing , Zheng Jiang , Zhou Hong 
Published: February 2020

AbstractBackground and PurposeImmunosuppression is the predominant cause of mortality for sepsis due to failure to eradicate invading pathogens. Unfortunately, no effective and specific drugs capable of reversing immunosuppression are available for clinical use. Increasing evidence implicates vitamin D receptor (VDR) involved in sepsis-induced immunosuppression. Herein, artesunate (AS) was discovered to reverse sepsis-induced immunosuppression and its molecular mechanism is investigated.Experimental ApproachEffect of artesunate on sepsis-induced immunosuppression was investigated in mice andin vitro. VDR was predicted to be an interacted candidate of AS by bioinformatics predict, then identified using PCR and immunoblotting. VDR,ATG16L1and NF-κB p65 were modified to investigate the alteration of AS’s effect on pro-inflammatory cytokines release, bacteria clearance and autophagy activities in sepsis-induced immunosuppression.Key ResultsAS significantly reduced the mortality of cecal ligation and puncture (CLP)-induced sepsis immunosuppression mice challenged withPseudomonas Aeruginosa, and enhanced proinflammatory cytokines release and bacterial clearance to reverse sepsis-induced immunosuppressionin vivoandin vitro. Mechanically, AS interacted with VDR thereby inhibited the nuclear translocation of VDR, then influencingATG16L1transcription and subsequent autophagy activity. In addition, AS inhibited physical interaction between VDR and NF-κB p65 in LPS tolerance macrophages, then promoted nuclear translocation of NF-κB p65, which activated the transcription of NF-κB p65 target genes such as pro-inflammatory cytokines.Conclusion and ImplicationsOur findings provide an evidence that AS interacted with VDR to reverse sepsis-induced immunosuppression in an autophagy and NF-κB dependent way, highlighting a novel approach for sepsis treatment and drug repurposing of AS in the future.
Stimulus transformation into motor action: dynamic graph analysis reveals a posterior-to-anterior shift in brain network communication of older subjects
Authors: Rosjat Nils , Wang Bin A. , Liu Liqing , Fink Gereon R. , Daun Silvia 
Published: February 2020

AbstractCognitive performance slows down with increasing age. This includes cognitive processes that are essential for the performance of a motor act, such as the slowing down in response to an external stimulus. The objective of this study was to identify aging-associated functional changes in the brain networks that are involved in the transformation of external stimuli into motor action. To investigate this topic, we employed dynamic graphs based on phase-locking of Electroencephalography signals recorded from healthy younger and older subjects while performing a simple visually-cued finger-tapping task. The network analysis yielded specific age-related network structures varying in time in the low frequencies (2-7 Hz), which are closely connected to stimulus processing, movement initiation and execution in both age groups. The networks in older subjects, however, contained several additional, particularly interhemispheric, connections and showed an overall increased coupling density. Cluster analyses revealed reduced variability of the subnetworks in older subjects, particularly during movement preparation. In younger subjects, occipital, parietal, sensorimotor and central regions were - temporally arranged in this order - heavily involved in hub nodes. Whereas in older subjects, a hub in frontal regions preceded the noticeably delayed occurrence of sensorimotor hubs, indicating different neural information processing in older subjects.All observed changes in brain network organization, which are based on neural synchronization in the low frequencies, provide a possible neural mechanism underlying previous fMRI data, which report an overactivation, especially in the prefrontal and pre-motor areas, associated with a loss of hemispheric lateralization in older subjects.
Dissimilarity-Overlap Analysis of Replicate Enrichment Communities
Authors: Vila Jean C. C. , Liu Yang-Yu , Sanchez Alvaro 
Published: February 2020

AbstractThe taxonomic composition of microbial communities can vary substantially between individual hosts and within the same host over time. Efforts to build quantitative and predictive models of microbial population dynamics are underway, but fundamental questions remain. How different are population dynamics in different hosts? Do communities that share the same taxa also exhibit identical dynamics? In vitro communities can help establish baseline expectations that are critical towards resolving these questions in natural communities. Here, we applied a recently developed tool, Dissimilarity-Overlap Analysis (DOA), to a set of experimental in vitro communities that differed in nutrient composition. The Dissimilarity and Overlap of these communities are negatively correlated in replicate habitats, as one would expect if microbial population dynamics were on average strongly convergent (or “universal”) across these replicate habitats. However, the existence of such a negative correlation does not necessarily imply that population dynamics are always universal in all communities. Even in replicate, identical habitats, two different communities may contain the same set of taxa at different abundances in equilibrium. The formation of alternative states in community assembly is strongly associated with the presence of specific taxa in the communities. Our results benchmark DOA, providing support for some of its core assumptions, and suggest that communities sharing the same taxa and external abiotic factors generally (but not necessarily) have a negative correlation between Dissimilarity and Overlap.
Deciphering and modelling the TGF-β signalling interplays specifying the dorsal-ventral axis of the sea urchin embryo
Authors: Floc’hlay Swann , Molina Maria Dolores , Hernandez Céline , Haillot Emmanuel , Thomas-Chollier Morgane , Lepage Thierry , Thieffry Denis 
Published: February 2020

AbstractDuring sea urchin development, secretion of Nodal and BMP2/4 ligands and their antagonists Lefty and Chordin from a ventral organizer region specifies the ventral and dorsal territories. This process relies on a complex interplay between the Nodal and BMP pathways through numerous regulatory circuits. To decipher the interplay between these pathways, we used a combination of treatments with recombinant Nodal and BMP2/4 proteins and a computational modelling approach. We assembled a logical model focusing on cell responses to signalling inputs along the dorsal-ventral axis, which was extended to cover ligand diffusion and enable multicellular simulations. Our model simulations accurately recapitulate gene expression in wild type embryos, accounting for the specification of ventral ectoderm, ciliary band and dorsal ectoderm. Our model simulations further recapitulate various morphant phenotypes, reveals a dominance of the BMP pathway over the Nodal pathway, and stresses the crucial impact of the rate of Smad activation in D/V patterning. These results emphasise the key role of the mutual antagonism between the Nodal and BMP2/4 pathways in driving early dorsal-ventral patterning of the sea urchin embryo.Summary StatementWe propose a predictive computational model of the regulatory network controlling the dorsal-ventral axis specification in sea urchin embryos, and highlight key features of Nodal and BMP antagonism.
Myosin 1b Flattens and Prunes Branched Actin Filaments
Authors: Pernier Julien , Morchain Antoine , Caorsi Valentina , Bertin Aurélie , Bousquet Hugo , Bassereau Patricia , Coudrier Evelyne 
Published: February 2020

AbstractMotile and morphological cellular processes require a spatially and temporally coordinated branched actin network that is controlled by the activity of various regulatory proteins including the Arp2/3 complex, profilin, cofilin and tropomyosin. We have previously reported that myosin 1b regulates the density of the actin network in the growth cone. Usingin vitroF-actin gliding assays and total internal reflection fluorescence (TIRF) microscopy we show in this report that this molecular motor flattens the Arp2/3-dependent actin branches up to breaking them and reduces the probability to form new branches. This experiment reveals that myosin 1b can produce force sufficient enough to break up the Arp2/3-mediated actin junction. Together with the formerin vivostudies, this work emphasizes the essential role played by myosins in the architecture and in the dynamics of actin networks in different cellular regions.Short summaryUsingin vitroF-actin gliding assays and total internal reflection fluorescence (TIRF) microscopy we show that myosin flattens the Arp2/3-dependent actin branches up to breaking them and reduces the probability to form new branches
A systematic, label-free method for identifying RNA-associated proteinsin vivoprovides insights into vertebrate ciliary beating
Authors: Drew Kevin , Lee Chanjae , Cox Rachael M. , Dang Vy , Devitt Caitlin C. , Papoulas Ophelia , Huizar Ryan L. , Marcotte Edward M. , Wallingford John B. 
Published: February 2020

AbstractCell-type specific RNA-associated proteins (RAPs) are essential for development and homeostasis in animals. Despite a massive recent effort to systematically identify RAPs, we currently have few comprehensive rosters of cell-type specific RAPs in vertebrate tissues. Here, we demonstrate the feasibility of determining the RNA-interacting proteome of a defined vertebrate embryonic tissue using DIF-FRAC, a systematic and universal (i.e., label-free) method. Application of DIF-FRAC to cultured tissue explants ofXenopusmucociliary epithelium identified dozens of known RAPs as expected, but also several novel RAPs, including proteins related to assembly of the mitotic spindle and regulation of ciliary beating. In particular, we show that the inner dynein arm tether Cfap44 is an RNA-associated protein that localizes not only to axonemes, but also to liquid-like organelles in the cytoplasm called DynAPs. This result led us to discover that DynAPs are generally enriched for RNA. Together, these data provide a useful resource for a deeper understanding of mucociliary epithelia and demonstrate that DIF-FRAC will be broadly applicable for systematic identification of RAPs from embryonic tissues.
Identification of viruses from fungal transcriptomes
Authors: Jo Yeonhwa , Choi Hoseong , Chu Hyosub , Cho Won Kyong 
Published: February 2020

ABSTRACTViruses infecting fungi are referred to as mycoviruses. Here, we carried outin silicomycovirome studies using public fungal transcriptomes. We identified 468 virus-associated contigs assigned to five orders, 21 families, 26 genera, and 88 species. We assembled 120 viral genomes with diverse RNA and DNA genomes. The phylogenetic tree and genome organization unveiled the possible host origin of mycovirus species and diversity of their genome structures. Most identified mycoviruses were originated from fungi; however, some mycoviruses had strong phylogenetic relationships with those from insects and plants. The viral abundance and mutation frequency of mycoviruses were very low; however, the compositions and populations of mycoviruses were very complex. Although coinfection of diverse mycoviruses in the fungi was common in our study, most mycoviromes had a dominant virus species. The compositions and populations of mycoviruses were more complex than we expected.Moniliniaviromes revealed that there were strong deviations in the composition of viruses and viral abundance among samples.Gigasporaviromes showed that the chemical strigolactone might promote virus replication and mutations, while symbiosis with endobacteria might suppress virus replication and mutations. This study revealed the diversity and host distribution of mycoviruses.
CRISPR Screen in Regulatory T Cells Reveals Ubiquitination Modulators of Foxp3
Authors: Cortez Jessica T. , Montauti Elena , Shifrut Eric , Zhang Yusi , Shaked Oren , Xu Yuanming , Roth Theodore L. , Simeonov Dimitre R. , Zhang Yana , Chen Siqi , Li Zhongmei , Vogel Ian A. , Prator Grace Y. , Zhang Bin , Lee Youjin , Sun Zhaolin , Ifergan Igal , Van Gool Frédéric , Bluestone Jeffrey A. , Marson Alexander , Fang Deyu 
Published: February 2020

AbstractRegulatory T cells (Tregs) are required to control immune responses and maintain homeostasis but are a significant barrier to anti-tumor immunity1. Conversely, Treg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of pro-inflammatory properties2, can promote autoimmunity and/or facilitate more effective tumor immunity3,4. A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective Treg therapies for autoimmune disease and cancer. Despite improved functional genetic tools that now allow for systematic interrogation, dissection of the gene regulatory programs that modulate Foxp3 expression has not yet been reported. In this study, we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse Tregs and applied this technology to perform a targeted loss-of-function screen of ∼490 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We discovered several novel modulators including ubiquitin-specific peptidase 22 (Usp22), Ataxin 7 like 3 (Atxn7l3) and ring finger protein 20 (Rnf20). Members of the deubiquitination module of the SAGA chromatin modifying complex, Usp22 and Atxn7l3, were discovered to be positive regulators that stabilized Foxp3 expression; whereas the screen suggested Rnf20, an E3 ubiquitin ligase, is a negative regulator of Foxp3. Treg-specific ablation of Usp22 in mice reduced Foxp3 protein and created defects in their suppressive function that led to spontaneous autoimmunity but protected against tumor growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient Tregs could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in Tregs. These results reveal novel modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for Treg immunotherapies for cancer and autoimmune disease.
Joint profiling of DNA and proteins in single cells to dissect genotype-phenotype associations in leukemia
Authors: Demaree Benjamin , Delley Cyrille L. , Vasudevan Harish N. , Peretz Cheryl A.C. , Ruff David , Smith Catherine C. , Abate Adam R. 
Published: February 2020

AbstractStudies of acute myeloid leukemia rely on DNA sequencing and immunophenotyping by flow cytometry as primary tools for disease characterization. However, leukemia tumor heterogeneity complicates integration of DNA variants and immunophenotypes from separate measurements. Here we introduce DAb-seq, a novel technology for simultaneous capture of DNA genotype and cell surface phenotype from single cells at high throughput, enabling direct profiling of proteogenomic states in tens of thousands of cells. To demonstrate the approach, we analyze the disease of three patients with leukemia over multiple treatment timepoints and disease recurrences. We observe complex genotype-phenotype dynamics that illustrate the subtlety of the disease process and the degree of incongruity between blast cell genotype and phenotype in different clinical scenarios. Our results highlight the importance of combined single-cell DNA and protein measurements to fully characterize the heterogeneity of leukemia.
Quality control and processing of nascent RNA profiling data
Authors: Smith Jason P. , Dutta Arun B. , Sathyan Kizhakke Mattada , Guertin Michael J. , Sheffield Nathan C. 
Published: February 2020

Nascent RNA profiling is growing in popularity; however, there is no standard analysis pipeline to uniformly process the data and assess quality. Here, we introduce PEPPRO, a comprehensive, scalable work-flow for GRO-seq, PRO-seq, and ChRO-seq data. PEPPRO produces uniformly processed output files for downstream analysis and assesses adapter abundance, RNA integrity, library complexity, nascent RNA purity, and run-on efficiency. PEPPRO is restartable and fault-tolerant, records copious logs, and provides a web-based project report. PEPPRO can be run locally or using cluster, providing a portable first step for genomic nascent RNA analysis.AvailabilityBSD2-licensed code and documentation: https://peppro.databio.org.
Increasing proteome coverage using cysteine-specific DIA Mass spectrometry – Cys-DIA
Authors: Tahir Muhammad , Nawrocki Arkadiusz , Ditzel Henrik J. , Larsen Martin R. 
Published: February 2020

AbstractWe report a Data Independent Analysis (DIA) mass spectrometric method for quantitative proteomics based on cysteine-containing peptides derived by tryptic digestion from biological samples (termed Cys-DIA). This technology significantly increases the coverage of the identifiable and quantifiable proteome in DIA/SWATH analyses by >35% compared to the conventional DIA/SWATH methods. The strategy was applied here to illustrate the quantitative difference in the proteome between isogenic human cancer cell lines with different metastatic capabilities.
Brain disconnections link structural connectivity with function and behaviour
Authors: de Schotten Michel Thiebaut , Foulon Chris , Nachev Parashkev 
Published: February 2020

AbstractBrain lesions do not just disable but also disconnect brain areas, which once deprived of their input or output, can no longer subserve behaviour and cognition. The role of white matter connections has remained an open question for the past 250 years. Based on 1333 stroke lesions we reveal the human Disconnectome and demonstrate its relationship to the functional segregation of the human brain. Results indicate that functional territories are not only defined by white matter connections, but also by the highly stereotyped spatial distribution of brain disconnections. While the former has granted us the possibility to map 590 functions on the white matter of the whole brain, the latter compels a revision of the taxonomy of brain functions. Overall, our freely available Functional Atlas of the White Matter will enable improved clinical-neuroanatomical predictions for brain lesion studies and provide a platform for novel explorations in the domain of cognition.
FreiPose: A Deep Learning Framework for Precise Animal Motion Capture in 3D Spaces
Authors: Zimmermann Christian , Schneider Artur , Alyahyay Mansour , Brox Thomas , Diester Ilka 
Published: February 2020

AbstractThe increasing awareness of the impact of spontaneous movements on neuronal activity has raised the need to track behavior. We present FreiPose, a versatile learning-based framework to directly capture 3D motion of freely definable points with high precision (median error < 3.5% body length, 41.9% improvement compared to state-of-the-art) and high reliability (82.8% keypoints within < 5% body length error boundary, 72.0% improvement). The versatility of FreiPose is demonstrated in two experiments: (1) By tracking freely moving rats with simultaneous electrophysiological recordings in motor cortex, we identified neuronal tuning to behavioral states and individual paw trajectories. (2) We inferred time points of optogenetic stimulation in rat motor cortex from the measured pose across individuals and attributed the stimulation effect automatically to body parts. The versatility and accuracy of FreiPose open up new possibilities for quantifying behavior of freely moving animals and may lead to new ways of setting up experiments.
A synthetic synaptic organizer protein restores glutamatergic neuronal circuits
Authors: Suzuki Kunimichi , Elegheert Jonathan , Song Inseon , Sasakura Hiroyuki , Senkov Oleg , Kakegawa Wataru , Clayton Amber J. , Chang Veronica T. , Ferrer-Ferrer Maura , Miura Eriko , Kaushik Rahul , Ikeno Masashi , Morioka Yuki , Takeuchi Yuka , Shimada Tatsuya , Otsuka Shintaro , Stoyanov Stoyan , Watanabe Masahiko , Takeuchi Kosei , Dityatev Alexander , Aricescu A. Radu , Yuzaki Michisuke 
Published: February 2020

AbstractNeuronal synapses undergo structural and functional changes throughout life, essential for nervous system physiology. However, these changes may also perturb the excitatory/inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we report the design and characterization of CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1 to interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors. CPTX induced the formation of excitatory synapsesin vitroandin vivoand restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer’s disease and spinal cord injury, respectively. Thus, CPTX represents a prototype for novel structure-guided biologics that can efficiently repair or remodel neuronal circuits.One Sentence SummaryStructural biology information was used to design CPTX, a synthetic protein that induces functional excitatory synapses and restores normal behaviors in mouse models of neurological diseases.
Dose-dependent phorbol 12-myristate-13-acetate-mediated monocyte-to-macrophage differentiation induces unique proteomic signatures in THP-1 cells
Authors: Pinto Sneha M. , Kim Hera , Subbannayya Yashwanth , Giambelluca Miriam , Bösl Korbinian , Kandasamy Richard K. 
Published: February 2020

AbstractMacrophages are sentinels of the innate immune system, and the human monocytic cell line THP-1 is one of the widely usedin vitromodels to study immune responses. Several monocyte-to-macrophage differentiation protocols exist, with phorbol 12-myristate-13-acetate (PMA) being the widely used and accepted method. However, the concentrations and duration of PMA treatment vary widely in the published literature and their effect on protein expression is not fully deciphered. In this study, we employed a dimethyl labeling-based quantitative proteomics approach to determine the changes in the protein repertoire of macrophage-like cells differentiated from THP-1 monocytes by three commonly used PMA-based differentiation protocols. Our analysis shows that variations in PMA concentration and duration of rest post-stimulation result in downstream differences in the protein expression and cellular processes. We demonstrate that these differences result in altered gene expression of cytokines upon stimulation with various TLR agonists. Together, these findings provide a valuable resource that significantly expands the knowledge of protein expression dynamics with one of the most commonin vitromodels for macrophages, which in turn has a profound impact on the immune responses being studied.