bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reward-based invigoration of sequential reaching
Authors: Sporn Sebastian , Chen Xiuli , Galea Joseph M 
Published: June 2020

AbstractSeeking reward is a powerful tool for shaping human behaviour. While it has been demonstrated that reward invigorates performance of simple movements, its effect on more complex sequential actions is less clear. In addition, it is unknown why reward-based improvements for discrete actions are transient, i.e. performance gains are lost once reward is removed, but appear long lasting for sequential actions. We show across three experiments that reward invigorates sequential reaching performance. Driven by a reward-based increase in speed, movements also exhibited greater coarticulation, smoothness and a closer alignment to a minimum jerk trajectory. Critically, these performance gains were maintained across multiple days even after the removal of reward. We propose that coarticulation, the blending together of sub-movements into a single continuous action, provides a mechanism by which reward can invigorate sequential performance whilst also increasing efficiency. This change in efficiency appears essential for the retention of reward-based improvements in motor behaviour.
Protein tyrosine phosphatase-PEST (PTP-PEST) mediates hypoxia-induced endothelial autophagy and angiogenesis through AMPK activation
Authors: Chandel Shivam , Manikandan Amrutha , Mehta Nikunj , Nathan Abel Arul , Tiwari Rakesh Kumar , Mohapatra Samar Bhallabha , Chandran Mahesh , Jaleel Abdul , Manoj Narayanan , Dixit Madhulika 
Published: June 2020

AbstractGlobal and endothelial loss of PTP-PEST is associated with impaired cardiovascular development and embryonic lethality. Although hypoxia is implicated in vascular morphogenesis and remodelling, its effect on PTP-PEST remains unexplored. Here we report that hypoxia (1% oxygen)increases protein levels and catalytic activity of PTP-PEST in primary endothelial cells. Immunoprecipitation followed by mass spectrometry (LC/MS/MS) revealed that AMP-activated protein kinase alpha subunits (AMPK α1and α2) interact with PTP-PEST under normoxia but not in hypoxia. Co-immunoprecipitation experiments confirmed this observation and determined that AMPK α subunits interact with the catalytic domain of PTP-PEST. Knock-down of PTP-PEST abrogated hypoxia mediated tyrosine dephosphorylation and activation of AMPK (Thr172phosphorylation). Absence of PTP-PEST also blocked hypoxia-induced autophagy (measured as LC3 degradation and puncta formation) which was rescued by AMPK activator, metformin (500µM). Since endothelial autophagy is a pre-requisite for angiogenesis, knock-down of PTP-PEST also attenuated endothelial cell migration and capillary tube formation with autophagy inducer rapamycin (200nM) rescuing these effects. In conclusion, this work identifies for the first time PTP-PEST as a regulator of hypoxia-induced AMPK activation and endothelial autophagy to promote angiogenesis.
Passive Novel Isodamping Dynamometer for Mobile Measurement of Plantar Flexor Function
Authors: Drazan John F. , Hullfish Todd J , Baxter Josh R. 
Published: June 2020

ABSTRACTIsokinetic dynamometers are the gold standard tools used to assessin vivojoint and muscle function in human subjects, however, the large size and high cost of these devices prevents their widespread use outside of biomechanics lab. In this study, we developed a mobile dynamometer to allow for field measurements of joint level function. To ensure subject safety, we designed a new “isodamping” dynamometer that acted as passive energy sink which constrains velocity by forcing incompressible oil through an orifice with an adjustable diameter. We validated the performance of this device by testing plantar flexor function in six healthy adults on both a commercial isokinetic dynamometer and this novel device at three velocities/damper settings and at three different effort levels. During maximal effort contraction, measurements of peak moment and velocity at peak moment of the novel device and the commercial device were strongly correlated along the predicted quadratic line (R2> 0.708,p≤ 0.008). The setting of the damper prescribed the relationship between peak moment and velocity at peak moment across all subjects and effort levels (R2> 0.91,p< 0.001). The novel device was significantly smaller (0.75 m2footprint), lighter (30 kg), and lower cost (~$2,200 US) than commercial devices compared to commercially-available isokinetic dynamometers (5.95 m2footprint, 450 kg, and ~$40,000 US respectively).
Stick Stippling for Joint 3D Visualization of Diffusion MRI Fiber Orientations and Density
Authors: Cabeen Ryan P. , Laidlaw David H. , Toga Arthur W. 
Published: June 2020

AbstractThis paper investigates a stick stippling approach for glyph-based visualization of complex neural fiber architecture derived from diffusion magnetic resonance imaging. The presence of subvoxel crossing fibers in the brain has prompted the development of advanced modeling techniques; however, there remains a need for improved visualization techniques to more clearly convey their rich structure. While tractography can illustrate large scale anatomy, visualization of diffusion models can provide a more complete picture of local anatomy without the known limitations of tracking. We identify challenges and evaluate techniques for visualizing multi-fiber models and identified techniques that improve on existing methods. We conducted experiments to compare these representations and evaluated them within vivodiffusion MR datasets that vary in voxel resolution and anisotropy. We found that stick rendering as 3D tubes increased legibility of fiber orientation and that encoding fiber density by tube radius reduced clutter and reduced dependence on viewing orientation. Furthermore, we identified techniques to reduce the negative perceptual effects of voxel gridding through a jittering and re-sampling approach to produce a stippling effect. Looking forward, this approach provides a new way to explore diffusion MRI datasets that may aid in the visual analysis of white matter fiber architecture and microstructure. Our software implementation is available in the Quantitative Imaging Toolkit (QIT).
Papiliotrema maritimif.a. sp. nov., a new tremellaceous yeast species associated to macrophytes in a Marshland of South Brazil
Authors: Ramírez-Castrillón Mauricio , Gomes Fernanda Fraga , de Souza Andrea Formoso , Leite Belize Rodrigues , Pagani Danielle Machado , Valente Patricia 
Published: June 2020

AbstractOne new yeast species,Papiliotrema maritimisp. nov., is being proposed to be suitable into the Rhynchogastremataceae family, belonging to the Tremellales clade. This new species is related to six others from thePapiliotremagenus:P. taeanensis, P. siamense, P. perniciosus, P. nemorosus, P. bandonii, P. japonicaandP. fuscus. The novel species is proposed based on the phylogenetic species concept through analysis of the D1/D2 region, part of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region. A total of 11 strains ofPapiliotrema maritimisp. nov. were obtained from macrophytes leaves collected in south Brazil.Papiliotrema maritimisp. nov. differs by 12, 15, 25, 25, 25 and 29 substitutions in the D1/D2 domain from the relatedspecies P. fuscus, P. japonica, P. siamense, P. nemorosus, P. bandonii, and P. perniciosus, respectively. Concerning the ITS region, there are 11 substitutions and 52 or more substitutions when compared toP. teanensisand its closest relatives. The type strain ofPapiliotrema maritimisp. nov. is UFMG-CM-Y6048. The MycoBank number forPapiliotrema maritimisp. nov. is MB 835603.
Chemical Systems Biology Reveals Mechanisms of Glucocorticoid Receptor Signaling
Authors: Bruno Nelson E. , Nwachukwu Jerome C. , Srinivasan Sathish , Nettles Charles C. , Izard Tina , Jin Zhuang , Boregowda Siddaraju V. , Phinney Donald G. , Elemento Olivier , Liu Xu , Ortlund Eric A. , Houtman René , Stavreva Diana A. , Hager Gordon L. , Kamenecka Theodore M. , Kojetin Douglas J. , Nettles Kendall W. 
Published: June 2020

AbstractGlucocorticoids display remarkable anti-inflammatory activity, but their use is limited by on-target adverse effects including insulin resistance and skeletal muscle atrophy. We used a chemical systems biology approach, Ligand Class Analysis (LCA), to examine ligands designed to modulate glucocorticoid receptor activity through distinct structural mechanisms. These ligands displayed diverse activity profiles, providing the variance required to identify target genes and coregulator interactions that were highly predictive of their effects on myocyte glucose disposal and protein balance. Their anti-inflammatory effects were linked to glucose disposal but not muscle atrophy. This approach also predicted selective modulationin vivo, identifying compounds that were muscle sparing or anabolic for protein balance and mitochondrial potential. LCA defined the mechanistic links between the ligand-receptor interface and ligand-driven physiological outcomes, a general approach that can be applied to any ligand-regulated allosteric signaling system.
Surprising amount of stasis in repetitive genome content across the Brassicales
Authors: Beric Aleksandra , Mabry Makenzie E. , Harkess Alex E. , Schranz M. Eric , Conant Gavin C. , Edger Patrick P. , Meyers Blake C. , Pires J. Chris 
Published: June 2020

ABSTRACTGenome size of plants has long piqued the interest of researchers due to the vast differences among organisms. However, the mechanisms that drive size differences have yet to be fully understood. Two important contributing factors to genome size are expansions of repetitive elements, such as transposable elements (TEs), and whole-genome duplications (WGD). Although studies have found correlations between genome size and both TE abundance and polyploidy, these studies typically test for these patterns within a genus or species. The plant order Brassicales provides an excellent system to test if genome size evolution patterns are consistent across larger time scales, as there are numerous WGDs. This order is also home to one of the smallest plant genomes,Arabidopsis thaliana- chosen as the model plant system for this reason - as well as to species with very large genomes. With new methods that allow for TE characterization from low-coverage genome shotgun data and 71 taxa across the Brassicales, we find no correlation between genome size and TE content, and more surprisingly we identify no significant changes to TE landscape following WGD.
Morphogenesis of the islets of Langerhans is guided by extra-endocrine Slit2/3 signals
Authors: Gilbert Jennifer M. , Adams Melissa T. , Sharon Nadav , Jayaraaman Hariharan , Blum Barak 
Published: June 2020

AbstractThe spatial architecture of the islets of Langerhans is vitally important for their correct function, and alterations in islet morphogenesis often result in diabetes mellitus. We have previously reported that Roundabout (Robo) receptors are required for proper islet morphogenesis. As part of the Slit-Robo signaling pathway, Robo receptors work in conjunction with Slit ligands to mediate axon guidance, cell migration, and cell positioning in development. However, the role of Slit ligands in islet morphogenesis has not yet been determined. Here we report that Slit ligands are expressed in overlapping and distinct patterns in both endocrine and non-endocrine tissues in late pancreas development. We show that function of either Slit2 or Slit3, which are predominantly expressed in the pancreatic mesenchyme, is required and sufficient for islet morphogenesis, while Slit1, which is predominantly expressed in the β cells, is dispensable for islet morphogenesis. We further show that Slit functions as a repellent signal to β cells. These data suggest that clustering of endocrine cells during islet morphogenesis is guided, at least in part, by repelling Slit2/3 signals from the pancreatic mesenchyme.
Cellular debris, not mucilage polysaccharides, dominate extracts ofPlantago ovataandPlantago lanceolatacalli grownin vitro
Authors: Cowley James M. , Herliana Lina , Betts Natalie S. , Burton Rachel A. 
Published: June 2020

AbstractMucilage is a hydrophilic mixture of polysaccharides produced by seeds of many species, and used in research, industrial processes and as human health supplements. As such, demand often outweighs supply. In recent years, several researchers have reported that mucilage can be produced efficiently fromin vitro-cultured calli as a direct ‘plant-less’ alternative to seed mucilage; however, this mucilage has not been rigorously characterised. Here we replicate previously published culturing and extraction procedures and couple them with compositional analysis to determine whether the mucilage produced fromPlantago ovataandP. lanceolatacalli are similar to seed mucilage. Our monosaccharide profiling and microscopy show that, while calli derived from either seedling hypocotyls or roots yield more material than seeds using the same extraction techniques, the majority of extract mass is cellular debris. Debris polysaccharide composition was significantly different to seed mucilage from both species. Plant tissue culture as an alternative source of high yields of useful mucilage polysaccharides, at least by these and similar methods, is likely to not be possible.
GlypNirO: An automated workflow for quantitativeN- andO-linked glycoproteomic data analysis
Authors: Phung Toan K. , Pegg Cassandra L. , Schulz Benjamin L. 
Published: June 2020

AbstractMass spectrometry glycoproteomics is rapidly maturing, allowing unprecedented insights into the diversity and functions of protein glycosylation. However, quantitative glycoproteomics remains challenging. We developed GlypNirO, an automated software pipeline which integrates the complementary outputs of Byonic and Proteome Discoverer to allow high-throughput automated quantitative glycoproteomic data analysis. The output of GlypNirO is clearly structured, allowing manual interrogation, and is also appropriate for input into diverse statistical workflows. We used GlypNirO to analyse a published plasma glycoproteome dataset and identified changes in site-specificN- andO-glycosylation occupancy and structure associated with hepatocellular carcinoma as putative biomarkers of disease.
Integrated analysis of glycan and RNA in single cells
Authors: Minoshima Fumi , Ozaki Haruka , Odaka Haruki , Tateno Hiroaki 
Published: June 2020

ABSTRACTSingle-cell sequencing has emerged as an indispensable technology to dissect cellular heterogeneity but never been applied to the simultaneous analysis of glycan and RNA. Using oligonucleotide-labeled lectins, we first established lectin-based glycan profiling of single cells by sequencing (scGlycan-seq). We then combined the scGlycan-seq with single-cell transcriptome profiling (scRNA-seq) for joint analysis of glycan and RNA in single cells (scGR-seq). Using scGR-seq, we analyzed the two modalities in human induced pluripotent stem cells (hiPSCs) before and after differentiation into neural progenitor cells at the single cell resolution. The combination of RNA and glycan separated the two cell types clearer than either one of them. Furthermore, integrative analysis of glycan and RNA modalities in single cells found known and novel lectins that were specific to hiPSCs and coordinated with neural differentiation. Taken together, we demonstrate that scGR-seq can reveal the cellular heterogeneity and biological roles of glycans across multicellular systems.
The Rab11 effectors Fip5 and Fip1 regulate zebrafish intestinal development
Authors: Jewett Cayla E. , Appel Bruce H. , Prekeris Rytis 
Published: June 2020

ABSTRACTThe Rab11 apical recycling endosome pathway is a well-established regulator of polarity and lumen formation; however, Rab11-vesicular trafficking also directs a diverse array of other cellular processes, raising the question of how Rab11 vesicles achieve specificity in space, time, and content of cargo delivery. In part, this specificity is achieved through effector proteins, yet the role of Rab11 effector proteinsin vivoremains vague. Here, we use CRISPR/Cas9 gene editing to study the role of the Rab11 effector Fip5 during zebrafish intestinal development. Zebrafish contain two paralogous genes,fip5aandfip5b, that are orthologs of humanFIP5. We find thatfip5aandfip5bmutant fish show phenotypes characteristic of microvillus inclusion disease, including microvilli defects, inclusion bodies, and lysosomal accumulation. Single and double mutant analysis suggest thatfip5aandfip5bfunction in parallel and regulate apical trafficking pathways required for assembly of keratin at the terminal web. Remarkably, in some genetic backgrounds, the absence of Fip5 triggers protein upregulation of a closely related family member, Fip1. This compensation mechanism occurs both during zebrafish intestinal development and in tissue culture models of lumenogenesis. In conclusion, our data implicate the Rab11 effectors Fip5 and Fip1 in a trafficking pathway required for apical microvilli formation.
A multiple ion-uptake phenotyping platform reveals shared mechanisms that affect nutrient uptake by maize roots
Authors: Griffiths Marcus , Roy Sonali , Guo Haichao , Seethepalli Anand , Huhman David , Ge Yaxin , Sharp Robert E. , Fritschi Felix B. , York Larry M. 
Published: June 2020

Nutrient uptake is critical for crop growth and determined by root foraging in soil. Growth and branching of roots lead to effective root placement to acquire nutrients, but relatively less is known about absorption of nutrients at the root surface from the soil solution. This knowledge gap could be alleviated by understanding sources of genetic variation for short-term nutrient uptake on a root length basis. A new modular platform for high-throughput phenotyping of multiple ion uptake kinetics was designed to determine nutrient uptake rates inZea mays. Using this system, uptake rates were characterized for the crop macronutrients nitrate, ammonium, potassium, phosphate and sulfate among the Nested Association Mapping (NAM) population founder lines. The data revealed that substantial genetic variation exists for multiple ion uptake rates in maize. Interestingly, specific nutrient uptake rates (nutrient uptake rate per length of root) were found to be both heritable and distinct from total uptake and plant size. The specific uptake rates of each nutrient were positively correlated with one another and with specific root respiration (root respiration rate per length of root), indicating that uptake is governed by shared mechanisms. We selected maize lines with high and low specific uptake rates and performed an RNA-seq analysis, which identified key regulatory components involved in nutrient uptake. The high-throughput multiple ion uptake kinetics pipeline will help further our understanding of nutrient uptake, parameterize holistic plant models, and identify breeding targets for crops with more efficient nutrient acquisition.Significance StatementNutrient uptake is among the most limiting factors for plant growth and yet has not been used as a selection criterion in breeding. This is partly due to the lack of high-throughput phenotyping methods for measuring nutrient uptake. Here we describe a novel high-throughput phenotyping pipeline for quantification of multiple ion uptake rates. Using this new phenotyping system, our results demonstrate that specific ion uptake performance by maize plants is positively correlated among the macronutrients nitrogen, phosphorus, potassium and sulfur, and that substantial variation exists within a genetically diverse population. The findings reveal components of regulatory pathways possibly related with enhanced uptake, and confirm that nutrient uptake itself is a potential target for breeding of nutrient-efficient crops.
Transforming the Language of Life: Transformer Neural Networks for Protein Prediction Tasks
Authors: Nambiar Ananthan , Liu Simon , Hopkins Mark , Heflin Maeve , Maslov Sergei , Ritz Anna 
Published: June 2020

AbstractThe scientific community is rapidly generating protein sequence information, but only a fraction of these proteins can be experimentally characterized. While promising deep learning approaches for protein prediction tasks have emerged, they have computational limitations or are designed to solve a specific task. We present a Transformer neural network that pre-trains task-agnostic sequence representations. This model is fine-tuned to solve two different protein prediction tasks: protein family classification and protein interaction prediction. Our method is comparable to existing state-of-the art approaches for protein family classification, while being much more general than other architectures. Further, our method outperforms all other approaches for protein interaction prediction. These results offer a promising framework for fine-tuning the pre-trained sequence representations for other protein prediction tasks.
Isolation of protein N-terminal peptides by charge-mediated position-selective enrichment using strong cation exchange chromatography
Authors: Chang Chih-Hsiang , Chang Hsin-Yi , Rappsilber Juri , Ishihama Yasushi 
Published: June 2020

ABSTRACTWe developed a simple and rapid method to enrich protein N-terminal peptides, in which the protease TrypN is first employed to generate protein N-terminal peptides without Lys or Arg and internal peptides with two positive charges at their N-termini, and then the N-terminal peptides are separated from the internal peptides by means of CHArge-Mediated Position-selective (CHAMP) enrichment using strong cation exchange (SCX) chromatography. This CHAMP-SCX approach was applied to 20 μg of human HEK293T cell lysate proteins to profile the N-terminal proteome. On average, 1,550 acetylated and 200 unmodified protein N-terminal peptides were successfully identified in a single LC/MS/MS run with less than 3% contamination with internal peptides, even when we accepted only canonical protein N-termini registered in the Swiss-Prot database. Since this method involves only two steps, protein digestion and chromatographic separation, without the need for tedious chemical reactions, it should be useful for comprehensive profiling of protein N-termini, including proteoforms with neo-N-termini.