bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimizing biosignal recording sites for hybrid noninvasive brain/neural robot control
Authors: Cavallo Alessia , Roth Vincent , Haslacher David , Nann Marius , Soekadar Surjo R. 
Published: April 2020

AbstractNoninvasive brain/neural controlled robots are promising tools to improve autonomy and quality of life in severe paralysis, but require biosignal recordings, such as electroencephalography (EEG) and electrooculography (EOG), from various sites distributed over the user’s head. This limits the applicability and practicality of noninvasive brain/neural robot control on an everyday basis. It would thus be very desirable to minimize the number of necessary recording sites paving the way for miniaturized, headset-like EEG/EOG systems that users with hemiplegia can mount by themselves. Here, we introduce a novel EEG/EOG brain/neural robot control strategy using only scalp electrodes placed near cortical sensorimotor areas. The strategy was tested across 16 healthy volunteers engaging in an EEG/EOG brain/neural control task. Classification accuracies were compared using scalp electrodes only vs. the conventional electrode placements across the scalp and face. To evaluate whether cranial muscle artifacts impede classification accuracy, participants were asked to chew during the task. We found that brain/neural classification accuracy was comparable and that chewing did not impact classification accuracies when using scalp electrodes only. Our results suggest that the proposed new strategy allows for reliable EEG/EOG-based brain/neural robot control, a critical prerequisite to broaden the use of noninvasive brain/neural assistive and rehabilitative technologies.
Dynamic changes in the urine proteome of tumor-bearing mouse models of B16 melanoma and RM-1 prostate cancer
Authors: Li Lujun , Pan Xuanzhen , Liu Yongtao , Wang Ting , Gao Youhe 
Published: April 2020

AbstractUrine can accumulate changes and reflect early physiological and pathological changes of various diseases, such as tumors. Therefore, urine is an ideal source for identification of early biomarkers. In this study, melanoma and prostate cancer-bearing mouse models were established by subcutaneous injection of B16 and RM-1 cells, respectively. Urine samples were collected at four time points during tumor growth. Based on data-independent acquisition (DIA) technology, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for quantitative analysis. Compared with those before the injection of B16 cells, 38 human homologous differential proteins were identified, and 18 proteins were reported to be related to melanoma. Before the tumor was visible, there were 4 differential proteins, and all were reported to be related to melanoma. Compared with that before the injection of RM-1 cells, a total of 14 human homologous differential proteins were identified, and 9 proteins were reported to be associated with prostate cancer. Before the tumor was palpable, 9 proteins showed significant differences. There were significant differences between the two tumor-bearing models. Through the above experiments and analysis, we found that the urine proteome can reflect the changes in the development and provide early biomarkers of the two tumors and provide clues for the early clinical diagnosis of these diseases.
A Region of UNC-89 (obscurin) Lying Between Two Protein Kinase Domains is a Highly Elastic Spring Required for Proper Sarcomere Assembly
Authors: Qadota Hiroshi , Moody Jasmine C. , Lesanpezeshki Leila , Moncrief Taylor , Kitzler Deborah , Bhat Purnima Devaki , Vanapalli Siva A. , Oberhauser Andres F. , Benian Guy M. 
Published: April 2020

AbstractInC. elegans, unc-89encodes a set of giant multi-domain proteins (up 8,081 residues) localized to the M-lines of muscle sarcomeres and required for normal sarcomere organization and whole-animal locomotion. Multiple UNC-89 isoforms contain two protein kinase domains. There is conservation in arrangement of domains between UNC-89 and its two mammalian homologs, obscurin and SPEG: kinase, a non-domain region of 647-742 residues, Ig domain, Fn3 domain and a second kinase domain. In all three proteins, this non-domain “interkinase region” has low sequence complexity, high proline content and lacks predicted secondary structure. We report that a major portion of this interkinase (571 residues out of 647 residues) when examined by single molecule force spectroscopyin vitrodisplays the properties of a random coil and acts as an entropic spring. We used CRISPR/Cas9 to create nematodes carrying an in-frame deletion of the same 571-residue portion of the interkinase. These animals express normal levels of giant internally deleted UNC-89 proteins, and yet show severe disorganization of all portions of the sarcomere in body wall muscle. Super-resolution microscopy reveals extra, short-A-bands lying close to the outer muscle cell membrane and between normally spaced A-bands. Nematodes with this in-frame deletion show defective locomotion and muscle force generation. We designed our CRISPR-generated in-frame deletion to contain an HA tag at the N-terminus of the large UNC-89 isoforms. This HA tag results in normal organization of body wall muscle, but dis-organization of pharyngeal muscle, small body size, and reduced muscle force, likely due to poor nutritional uptake.HighlightsThe giant muscle proteins UNC-89 and its mammalian homologs have an ∼700 aa non-domain region lying between two protein kinase domainsBy single molecule force spectroscopy UNC-89 non-domain region is an elastic random coilNematodes lacking this non-domain region have disorganized sarcomeres and reduced whole animal locomotionUNC-89 non-domain region is required for proper assembly of A-bands from thick filaments
Obtusaquinone is a cysteine modifying compound that targets Keap1 for degradation
Authors: Badr Christian E. , da Hora Cintia Carla , Kirov Aleksandar B. , Tabet Elie , Amante Romain , Nibbs Antoinette E. , Fitzsimons Evelyn , Chen John W. , Chiu Norman , Nakano Ichiro , Haas Wilhelm , Mazitschek Ralph , Tannous Bakhos A. 
Published: April 2020

ABSTRACTWe have previously identified the natural product Obtusaquinone (OBT) as a potent antineoplastic agent with promising in vivo activity in glioblastoma and breast cancer through the activation of oxidative stress; however, the molecular properties of this compound remained elusive. We used a multidisciplinary approach comprising medicinal chemistry, quantitative mass spectrometry-based proteomics, functional studies in cancer cells, pharmacokinetic analysis, as well as mouse xenograft models to develop and validate novel OBT analogs and charaterize the molecular mechanism of action of OBT. We here show that OBT and analogs, which have improved pharmacological properties, bind to cysteine residues with particular affinity to cysteine-rich Keap1, a member of the CUL3 ubiquitin ligase complex. This binding promotes an overall stress response and results in ubiquitination and proteasomal degradation of Keap1 and downstream activation of the Nrf2 pathway.
Hydrogen-deuterium exchange mass spectrometry captures distinct dynamics upon substrate and inhibitor binding to a transporter
Authors: Jia Ruyu , Martens Chloe , Shekhar Mrinal , Pant Shashank , Pellowe Grant A. , Lau Andy M. , Findlay Heather E. , Harris Nicola J. , Tajkhorshid Emad , Booth Paula J. , Politis Argyris 
Published: April 2020

AbstractProton-coupled transporters use transmembrane proton gradients to power active transport of nutrients inside the cell. High-resolution structures often fail to capture the coupling between proton and ligand binding, and conformational changes associated with transport. We combine HDX-MS with mutagenesis and MD simulations to dissect the molecular mechanism of the prototypical transporter XylE. We show that protonation of a conserved aspartate triggers conformational transition from outward-facing to inward-facing state. This transition only occurs in the presence of substrate xylose, while the inhibitor glucose locks the transporter in the outward-facing state. MD simulations corroborate the experiments by showing that only the combination of protonation and xylose binding, and not glucose, sets up the transporter for conformational switch. Overall, we demonstrate the unique ability of HDX-MS to distinguish between the conformational dynamics of inhibitor and substrate binding, and show that a specific allosteric coupling between substrate binding and protonation is a key step to initiate transport.
Programmable RNA Targeting using CasRx in Flies
Authors: Buchman Anna , Brogan Dan J. , Sun Ruichen , Yang Ting , Hsu Patrick , Akbari Omar S. 
Published: April 2020

AbstractCRISPR-Cas genome editing technologies have revolutionized the fields of functional genetics and genome engineering, but with the recent discovery and optimization of RNA-targeting Cas ribonucleases, we may soon see a similar revolution in the study of RNA function and transcriptome engineering. However, to date, successful proof-of-principle for Cas ribonuclease RNA targeting in eukaryotic systems has been limited. Only recently has successful modification of RNA expression by a Cas ribonuclease been demonstrated in animal embryos. This previous work, however, did not evaluate endogenous expression of Cas ribonucleases and only focused on Cas ribonuclease function in early developmental stages. A more comprehensive evaluation of this technology is needed to assess its potential impact in the field. Here we report on our efforts to develop a programmable platform for RNA-targeting using a Cas ribonuclease, CasRx, in the model organismDrosophila melanogaster. By genetically encoding CasRx in flies, we demonstrate moderate transcript targeting of known phenotypic genes in addition to unexpected toxicity and lethality. We also report on the off-target effects following on-target transcript cleavage by CasRx. Taken together, our results present the current state and limitations of a genetically encoded programmable RNA-targeting Cas system inDrosophila melanogaster, paving the way for future optimization of the system.
Whole-Brain opto-fMRI Map of Mouse VTA Dopaminergic Activation Reflects Structural Projections with Small but Significant Deviations
Authors: Ioanas Horea-Ioan , Saab Bechara John , Rudin Markus 
Published: April 2020

AbstractAscending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signalling in the mouse brain is crucial for the translational investigation of motivational control as well as of neuronal function phenotypes for diseases and interventions. In this article we use optogenetic stimulation directed at VTA dopaminergic neurons in combination with functional Magnetic Resonance Imaging (fMRI), a method widely used in human deep brain imaging. We present a comprehensive assay producing the first whole-brain opto-fMRI map of dopaminergic activation in the mouse, and show that VTA dopaminergic system function is consistent with its structural VTA projections, diverging only in a few key aspects. While the activation map predominantly highlights target areas according to their relative projection densities (e.g. strong activation of the nucleus accumbens and low activation of the hippocampus), it also includes areas for which a structural connection is not well established (such as the dorsomedial striatum). We further detail the variability of the assay with regard to multiple experimental parameters, including stimulation protocol and implant position, and provide evidence-based recommendations for assay reuse, publishing both reference results and a reference analysis workflow implementation.
FlexDotPlot: a universal and modular dot plot visualization tool for complex multifaceted data
Authors: Leonard Simon , Lardenois Aurélie , Tarte Karin , Rolland Antoine , Chalmel Frédéric 
Published: April 2020

AbstractMotivationDot plots are heatmap-like charts that provide a compact way to simultaneously display two quantitative information by means of dots of different sizes and colours. Despite the popularity of this visualization method, particularly in single-cell RNA-seq studies, existing tools used to make dot plots are limited in terms of functionality and usability.ResultsWe developed FlexDotPlot, an R package for generating dot plots from multifaceted data, including single-cell RNA-seq data. It provides a universal and easy-to-use solution with a high versatility. An interactive R Shiny application is also available allowing non-R users to easily generate dot plots with several tunable parameters.Availability and implementationSource code, detailed manual, and code to reproduce figures are available athttps://github.com/Simon-Leonard/FlexDotPlot. A Shiny app is available as a stand-alone application within the package.
Investigation in scanning beampattern generated by resonance cavities
Authors: Lu Hongwang , Ma Xin 
Published: April 2020

AbstractThe previous study has reported that the presence of a small flap in the Brown Long-Eared Bat (Plecotus auritus) generate useful spatial information by the frequency-driven beam scanning. However, it did not investigate the beampattern generating mechanism of the flap. In this study, according to the dipole equivalence principle, the two resonance cavities split by the flap are simplified to a dipole source with certain vibration orientation. The analytical solution of the dipole shows obvious frequency-driven sidelobe scanning in the beampattern, which matches the numerical results obtained from the pinna quite well. The results support the hypothesis that the frequency-driven sidelobe scanning is generated by the resonance in the two cavities split by the flap. This method can be applied to design a reflector antenna with small geometric structures for splitting existent resonance cavities to meet requirements of beam scanning.
Facile Synthesis and Metabolic Incorporation ofm-DAP Bioisosteres Into Cell Walls of Live Bacteria
Authors: Apostolos Alexis J. , Nelson Julia M. , Pires Marcos M. 
Published: April 2020

AbstractBacterial cell walls contain peptidoglycan (PG), a scaffold that provides proper rigidity to resist lysis from internal osmotic pressure and a barrier to protect cells against external stressors. It consists of repeating sugar units with a linkage to a stem peptide that becomes highly crosslinked by cell wall transpeptidases (TP). Because it is an essential component of the bacterial cell, the PG biosynthetic machinery is often the target of antibiotics. For this reason, cellular probes that advance our understanding of PG biosynthesis and its maintenance can be powerful tools to reveal novel drug targets. While synthetic PG fragments containing L-Lysine in the 3rdposition on the stem peptide are easier to access, those withmeso-diaminopimelic acid (m-DAP) pose a severe synthetic challenge. Herein, we describe a solid phase synthetic scheme based on the widely available Fmoc-protected L-Cysteine building block to assemblemeso-cystine (m-CYT), which mimics key structural features ofm-DAP. To demonstrate proper mimicry ofm-DAP, cell wall probes were synthesized withm-CYT in place ofm-DAP and evaluated for their metabolic processing in live bacterial cells. We found thatm-CYT-based cell wall probes were properly processed by TPs in various bacterial species that endogenously containm-DAP in their PG. We anticipate that this strategy, which is based on the use of inexpensive and commercially available building blocks, can be widely adopted to provide greater accessibility of PG mimics form-DAP containing organisms.
Spatio-temporal responses of butterflies to global warming on a Mediterranean island over two decades
Authors: Colom Pau , Traveset Anna , Carreras David , Stefanescu Constantí 
Published: April 2020

AbstractIn recent decades, efforts have been made to understand how global warming affects biodiversity and in this regard butterflies have emerged as a model group. The most conspicuous sign that warming is affecting the ecology of butterflies are the phenological advances occurring in many species. Moreover, rising temperatures are having a notable impact – both negative and positive – on population abundances. To date, patterns have generally been analysed at species level without taking into account possible differences between populations, which, when they are noted, are mostly attributed to large-scale climate differences across a latitudinal gradient. In this work, we use a long-term database of butterflies from the island of Menorca (Balearic Islands, Spain) to investigate how phenology and population dynamics have been affected by climate warming during the past two decades. In addition, we assess how responses are modulated by habitat characteristics and by species’ biological cycles. Our results show that species respond differently to warming at a local scale depending on season and habitat, and that coastal habitats in the Mediterranean region are particularly sensitive to the effects of climate change. Furthermore, our findings suggest that the effects of temperature could be partially offset in more inland habitats such as forests and deep ravines. The positive effect of temperature on ravine populations during the summer suggests that butterflies disperse across habitats as a response to rising temperatures during the season. This type of dispersal behaviour as a response to warming could be especially important in island ecosystems where the possibilities of modifying altitudinal or latitudinal distributions are often severely limited.
Genetic interaction between profilin and myosin II reveals a potential role for myosin II in actin filament disassemblyin vivo
Authors: Zambon Paola , Palani Saravanan , Jadhav Shekhar Sanjay , Gayathri Pananghat , Balasubramanian Mohan K. 
Published: April 2020

AbstractThe actin cytoskeleton plays a variety of roles in eukaryotic cell physiology, ranging from cell polarity and migration to cytokinesis. Key to the function of the actin cytoskeleton is the mechanisms that control its assembly, stability, and turnover. Through genetic analyses in fission yeast, we found that,myo2-S1(myo2-G515D), a myosin II mutant allele was capable of rescuing lethality caused by compromise of mechanisms involved in actin cable / ring assembly and stability. The mutation inmyo2-S1 affects the activation loop of Myosin II, which is involved in physical interaction with subdomain 1 of actin and in stimulating the ATPase activity of Myosin. Consistently, actomyosin rings inmyo2-S1 cell ghosts were severely compromised in contraction upon ATP addition, suggesting that Myo2-S1p was defective in actin binding and / or motor activity. These studies strongly suggest a role for Myo2p in actin cytoskeletal disassembly and turnover, and that compromise of this activity leads to genetic suppression of mutants defective in actin cable assembly / stability.
Analysis of Endothelial-to-Haematopoietic Transition at the Single Cell Level identifies Cell Cycle Regulation as a Driver of Differentiation
Authors: Canu Giovanni , Athanasiadis Emmanouil , Grandy Rodrigo A. , Garcia-Bernardo Jose , Strzelecka Paulina M. , Vallier Ludovic , Ortmann Daniel , Cvejic Ana 
Published: April 2020

ABSTRACTHaematopoietic stem cells (HSC) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematopoietic transition (EHT). Despite the progress achieved in recent years, the molecular mechanisms driving EHT are still poorly understood, especially in human where the AGM region is not easily accessible. In this study, we took advantage of a human pluripotent stem cell (hPSC) differentiation system and single-cell transcriptomics to recapitulate EHTin vitroand uncover mechanisms by which the haemogenic endothelium generates early haematopoietic cells. We show that most of the endothelial cells reside in a quiescent state and progress to the haematopoietic fate within a defined time window, within which they need to re-enter into the cell cycle. If cell cycle is blocked, haemogenic endothelial cells lose their EHT potential and adopt a non-haemogenic identity. Furthermore, we demonstrated that CDK4/6 and CDK1 play a key role not only in the transition but also in allowing haematopoietic progenitors to establish their full differentiation potential. Therefore, we propose a direct link between the molecular machineries that control cell cycle progression and EHT.
Hypergraphs for predicting essential genes using multiprotein complex data
Authors: Klimm Florian , Deane Charlotte M. , Reinert Gesine 
Published: April 2020

AbstractProtein-protein interactions are crucial in many biological pathways and facilitate cellular function. Investigating these interactions as a graph of pairwise interactions can help to gain a systemic understanding of cellular processes. It is known, however, that proteins interact with each other not exclusively in pairs but also in polyadic interactions and they can formmultiprotein complexes, which are stable interactions between multiple proteins. In this manuscript, we usehypergraphsto investigate multiprotein complex data. We investigate two random null models to test which hypergraph properties occur as a consequence of constraints, such as the size and the number of multiprotein complexes. We find that assortativity, the number of connected components, and clustering differ from the data to these null models. Our main finding is that projecting a hypergraph of polyadic interactions onto a graph of pairwise interactions leads to the identification of different proteins as hubs than the hyper-graph. We find in our data set that the hypergraph degree is a more accurate predictor for gene-essentiality than the degree in the pairwise graph. We find that analysing a hypergraph as pairwise graph drastically changes the distribution of the local clustering coefficient. Furthermore, using a pairwise interaction representing multiprotein complex data may lead to a spurious hierarchical structure, which is not observed in the hypergraph. Hence, we illustrate that hypergraphs can be more suitable than pairwise graphs for the analysis of multiprotein complex data.