bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic pathway prediction using non-negative matrix factorization with improved precision
Authors: Basher Abdur Rahman M. A. , McLaughlin Ryan J. , Hallam Steven J. 
Published: May 2020

AbstractMachine learning provides a probabilistic framework for metabolic pathway inference from genomic sequence information at different levels of complexity and completion. However, several challenges including pathway features engineering, multiple mapping of enzymatic reactions and emergent or distributed metabolism within populations or communities of cells can limit prediction performance. In this paper, we present triUMPF,triple non-negative matrix factorization (NMF) with community detection formetabolicpathway inference, that combines three stages of NMF to capture myriad relationships between enzymes and pathways within a graph network. This is followed by community detection to extract higher order structure based on the clustering of vertices which share similar statistical properties. We evaluated triUMPF performance using experimental datasets manifesting diverse multi-label properties, including Tier 1 genomes from the BioCyc collection of organismal Pathway/Genome Databases and low complexity microbial communities. Resulting performance metrics equaled or exceeded other prediction methods on organismal genomes with improved precision on multi-organismal datasets.Availability and implementationThe software package, and installation instructions are published ongithub.com/triUMPF
Survival on a semi-arid island: submersion and desiccation tolerances of fiddler crabs from the Galapagos Archipelago
Authors: Capparelli Mariana V. , Thurman Carl L. , Choueri Paloma Gusso , Abessa Denis Moledo , Fontes Mayana Karoline , Nobre Caio Rodrigues , McNamara John Campbell 
Published: May 2020

AbstractDuring tidal cycles, semi-terrestrial fiddler crabs are subject to alternating periods of submersion and desiccation. Here, we compare physiological and biochemical adjustments to forced submersion and desiccation in two fiddler crabs from the Galapagos archipelago: the indigenousLeptuca helleri, andMinuca galapagensis. We examine ecological distributions and habitat characteristics using transect analysis; survival after 6 h forced submersion at different salinities (0, 21 and 42 ‰S), and after 6 or 12 h desiccation challenge, including alterations in hemolymph osmolality; and, oxidative stress responses in the gills and hepatopancreas, accompanying glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) activities, and lipid peroxidase (LPO). We provide an integrated biomarker response (IBR) index for each species based on oxidative stress in each tissue and condition. Our transect study revealed thatL. hellerioccupies an intertidal niche whileM. galapagensisis supralittoral,L. helleribeing less resistant to submersion and desiccation. After 6 h submersion,L. hellerisurvived only at 21 ‰S whileM. galapagensissurvived at all salinities. Hemolymph osmolality decreased at 0 ‰S inM. galapagensis. After 6 h desiccation, osmolality decreased markedly inL. helleribut increased inM. galapagensis. Enzyme assays were not performed inL. helleriowing to high mortality on submersion/desiccation challenge. After submersion inM. galapagensis, hepatopancreas GPx activities decreased in 0 and 21 ‰S while GR activity was strongly inhibited at all salinities. Gill LPO decreased in 42 ‰S. On desiccation inL. helleri, GPx activity was inhibited in the hepatopancreas but increased in the gills. GST activity increased while LPO decreased in both tissues. After desiccation inM. galapagensis, hepatopancreas GPx activity increased. Both hepatopancreas and gill GST and GR activities and LPO were strongly inhibited. The IBR indexes forL. helleriwere highest in fresh caught crabs, driven by gill and hepatopancreas LPO. ForM. galapagensis, submersion at 21 ‰S contributed most to IBR, LPO in both tissues responding markedly.Leptuca helleriappears to be a habitat specialist adapted to a narrow set of niche dimensions whileM. galapagensissurvives over a much wider range, exhibiting little oxidative stress. The species’ physiological flexibilities and limitations provide insights into how fiddler crabs might respond to global environmental change on semi-arid islands.
Direct brain recordings identify hippocampal and cortical networks that distinguish successful versus failed episodic memory retrieval
Authors: Tan Ryan Joseph , Rugg Michael D. , Lega Bradley C. 
Published: May 2020

AbstractHuman data collected using noninvasive imaging techniques have established the importance of parietal regions towards episodic memory retrieval, including the angular gyrus and posterior cingulate cortex. Such regions comprise part of a putative core episodic retrieval network. In free recall, comparisons between contextually appropriate and inappropriate recall events (i.e. prior list intrusions) provide the opportunity to study memory retrieval networks supporting veridical recall, and existing findings predict that differences in electrical activity in these brain regions should be identified according to the accuracy of recall. However, prior iEEG studies, utilizing principally subdural grid electrodes, have not fully characterized brain activity in parietal regions during memory retrieval and have not examined connectivity between core recollection areas and the hippocampus or prefrontal cortex. Here, we employed a data set obtained from 100 human patients implanted with stereo EEG electrodes for seizure mapping purposes as they performed a free recall task. This data set allowed us to separately analyze activity in midline versus lateral parietal brain regions, and in anterior versus posterior hippocampus, to identify areas in which retrieval–related activity predicted the recollection of a correct versus an incorrect memory. With the wide coverage afforded by the stereo EEG approach, we were also able to examine interregional connectivity. Our key findings were that differences in gamma band activity in the angular gyrus, precuneus, posterior temporal cortex, and posterior (more than anterior) hippocampus discriminated accurate versus inaccurate recall as well as active retrieval versus memory search. The left angular gyrus exhibited a significant power decrease preceding list intrusions as well as unique phase-amplitude coupling properties, whereas the prefrontal cortex was unique in exhibiting a power increase during list intrusions. Analysis of connectivity revealed significant hemispheric asymmetry, with relatively sparse left– sided functional connections compared to the right hemisphere. One exception to this finding was elevated connectivity between the prefrontal cortex and left angular gyrus. This finding is interpreted as evidence for the engagement of prefrontal cortex in memory monitoring and mnemonic decision–making.
Were ancestral proteins less specific?
Authors: Wheeler Lucas C. , Harms Michael J. 
Published: May 2020

AbstractSome have hypothesized that ancestral proteins were, on average, less specific than their descendants. If true, this would provide a universal axis along which to organize protein evolution and suggests that reconstructed ancestral proteins may be uniquely powerful tools for protein engineering. Ancestral sequence reconstruction studies are one line of evidence used to support this hypothesis. Previously, we performed such a study, investigating the evolution of peptide binding specificity for the paralogs S100A5 and S100A6. The modern proteins appeared more specific than their last common ancestor (ancA5/A6), as each paralog bound a subset of the peptides bound by ancA5/A6. In the current study, we revisit this transition, using quantitative phage display to measure the interactions of 19,194 random peptides with human S100A5, S100A6, and ancA5/A6. This unbiased screen reveals a different picture. While S100A5 and S100A6 do indeed bind to a subset of the peptides recognized by ancA5/A6, they also acquired new peptide partners outside of the set recognized by ancA5/A6. Our previous work showed that ancA5/A6 had lower specificity than its descendants when measured against biological targets; our new work shows that ancA5/A6 has similar specificity to the modern proteins when measured against a random set of peptide targets. This demonstrates that altered biological specificity does not necessarily indicate altered intrinsic specificity, and sounds a cautionary note for using ancestral reconstruction studies with biological targets as a means to infer global evolutionary trends in specificity.
Common properties of visually-guided saccadic behavior and bottom-up attention in marmoset, macaque, and human
Authors: Chen Chih-Yang , Matrov Denis , Veale Richard , Onoe Hirotaka , Yoshida Masatoshi , Miura Kenichiro , Isa Tadashi 
Published: May 2020

AbstractThe saccade is a stereotypic behavior whose investigation improves our understanding of how primate brains implement precise motor control. Furthermore, saccades offer an important window into the cognitive and attentional state of the brain. Historically, saccade studies have largely relied on macaque. However, the cortical network giving rise to the saccadic command is difficult to study in macaque because relevant cortical areas lie in sulci and are difficult to access. Recently, a New World monkey – the marmoset – has garnered attention as an attractive alternative to macaque because of its smooth cortical surface, its smaller body, and its amenability to transgenic technology. However, adoption of marmoset for oculomotor research has been limited due to a lack of in-depth descriptions of marmoset saccade kinematics and their ability to perform psychophysical and cognitive tasks. Here, we directly compare free-viewing and visually-guided behavior of marmoset, macaque, and human engaged in identical tasks under similar conditions. In video free-viewing task, all species exhibited qualitatively similar saccade kinematics including saccade main sequence up to 25° in amplitude. Furthermore, the conventional bottom-up saliency model predicted gaze targets at similar rates for all species. We further verified their visually-guided behavior by training them with step and gap saccade tasks. All species showed similar gap effect and express saccades in the gap paradigm. Our results suggest that the three species have similar natural and task-guided visuomotor behavior. The marmoset can be trained on saccadic tasks and thus can serve as a model for oculomotor, attention, and cognitive research.New & noteworthyWe directly compared the results of video free-viewing task and visually-guided saccade tasks (step and gap) among three different species: the marmoset, macaque and human. We found that all species exhibit qualitatively similar saccadic behavior and bottom-up saliency albeit with small differences. Our results suggest that the marmoset possesses similar neural mechanisms to macaque and human for saccadic control, and it is an appropriate model animal to study neural mechanisms for active vision and attention.
Living apart together: modelling the consequences of the dikaryotic life cycle of mushroom-forming fungi for genomic conflict
Authors: Auxier Ben , Czaran Tamás , Aanen Duur K. 
Published: May 2020

AbstractGenerally, sexual organisms contain two haploid genomes, one from each parent, united in a single diploid nucleus of the zygote which links their fate during growth. A fascinating exception to this are Basidiomycete fungi, where the two haploid genomes remain separate in a dikaryon, retaining the option to fertilize subsequent monokaryons encountered. How the ensuing nuclear competition influences the balance of selection within and between individuals is largely unexplored. We test the consequences of the dikaryotic lifecycle for mating success and mycelium-level fitness components. We assume a tradeoff between mating fitness at the level of the haploid nucleus and fitness of the fungal mycelium. We show that the maintenance of fertilization potential by dikaryons leads to a higher proportion of fertilized monokaryons, but that the ensuing intra-dikaryon selection for increased nuclear mating fitness leads to reduced mycelium fitness relative to a diploid life cycle. However, this fitness reduction is lower compared to a hypothetical life cycle where dikaryons can also exchange nuclei. Prohibition of fusion between dikaryons therefore reduces the level of nuclear parasitism. The number of loci influencing fitness is an important determinant of the degree to which average mycelium-level fitness is reduced. The results of this study crucially hinge upon a tradeoff between nucleus and mycelium-level fitness. We discuss the evidence for this assumption and the implications of an alternative that there is a positive relationship between nucleus and mycelium-level fitness.
N-acetylaspartate improves cell survival when glucose is limiting
Authors: Alkan H. Furkan , Walter Katharina E. , Hackl Hubert , Vander Heiden Matthew G. , Madl Tobias , Bogner-Strauss Juliane G. 
Published: May 2020

SummaryN-acetylasparate (NAA), previously considered a brain-specific metabolite, is found in several cancers. However, whether it plays a role in tumor growth or survival is not fully understood. We provide evidence that NAA prevents cell death in low-glucose conditions via sustaining intracellular UDP-N-acetylglucosamine (UDP-GlcNac) levels, suppressing endoplasmic reticulum (ER) stress, and enabling continued protein synthesis. NAA production is critical forin vivotumor growth where lower glucose levels are present than those in cell culture. Furthermore, the breakdown of NAA leads to ER stress and cell death, suggesting that the role of NAA in low-glucose is independent of its catabolism to produce aspartate or acetate. Together, these data suggest NAA can support the growth of some tumors by helping them cope with glucose limitationsin vivo.HighlightsEndogenous N-acetylaspartate (NAA) production boosts tumor growthNAA supports cell survival in low glucose via suppressing ER stressBreaking down NAA limits tumor growth and induces ER stressin vivoThe role of NAA to rescue low glucose is independent of donating acetate or aspartateIn briefCancer cells need N-acetylaspartate to avoid ER stress and cell death when glucose availability is low.
Chronic Perinatal Hypoxia Delays Cardiac Maturation in a Mouse Model for Cyanotic Congenital Heart Disease
Authors: Romanowicz Jennifer , Dhari Zaenab , Guerrelli Devon , Mulvany Colm , Reilly Marissa , Swift Luther , Vasandani Nimisha , Ramadan Manelle , Ishibashi Nobuyuki , Posnack Nikki Gillum 
Published: May 2020

AbstractBackgroundCompared to acyanotic congenital heart disease (CHD), cyanotic CHD has an increased risk of lifelong mortality and morbidity. These adverse outcomes may be attributed to delayed cardiomyocyte maturation, since the transition from a hypoxic fetal milieu to oxygen rich postnatal environment is disrupted. We established a rodent model to replicate hypoxic myocardial conditions spanning perinatal development, and tested the hypothesis that chronic hypoxia impairs cardiac development.MethodsMouse dams were housed in hypoxia beginning at embryonic day 16. Pups stayed in hypoxia until postnatal day (P)8 when cardiac development is nearly complete. Global gene expression was quantified at P8 and at P30, after recovering in normoxia. Phenotypic testing included electrocardiogram, echocardiogram, andex-vivoelectrophysiology study.ResultsHypoxic animals were 48% smaller than controls. Gene expression was grossly altered by hypoxia at P8 (1427 genes affected), but normalized after recovery (P30). Electrocardiograms revealed bradycardia and slowed conduction velocity in hypoxic animals at P8, which resolved after recovery (P30). Notable differences that persisted after recovery (P30) included a 65% prolongation in ventricular effective refractory period, sinus node dysfunction, and a 24% reduction in contractile function in animals exposed to hypoxia.ConclusionsWe investigated the impact of chronic hypoxia on the developing heart. Perinatal hypoxia was associated with changes in gene expression and cardiac function. Persistent changes to the electrophysiologic substrate and contractile function warrant further investigation, and may contribute to adverse outcomes observed in the cyanotic CHD population.
Insulin-like growth factor 2 (IGF2) protects against Huntington’s disease through the extracellular disposal of protein aggregates
Authors: García-Huerta Paula , Troncoso-Escudero Paulina , Wu Di , Thiruvalluvan Arun , Cisternas Marisol , Henríquez Daniel R. , Plate Lars , Chana-Cuevas Pedro , Saquel Cristian , Thielen Peter , Longo Kenneth A. , Geddes Brad J. , Lederkremer Gerardo L. , Sharma Neeraj , Shenkman Marina , Naphade Swati , Ellerby Lisa M. , Sardi Pablo , Spichiger Carlos , Richter Hans G. , Court Felipe A. , Wiseman R. Luke , Gonzalez-Billault Christian , Bergink Steven , Vidal Rene L. , Hetz Claudio 
Published: May 2020

AbstractImpaired neuronal proteostasis is a salient feature of many neurodegenerative diseases, highlighting alterations in the function of the endoplasmic reticulum (ER). We previously reported that targeting the transcription factor XBP1, a key mediator of the ER stress response, delays disease progression and reduces protein aggregation in various models of neurodegeneration. To identify disease-modifier genes that may explain the neuroprotective effects of XBP1 deficiency, we performed gene expression profiling of brain cortex and striatum of these animals and uncovered insulin-like growth factor 2 (Igf2) as the major upregulated gene. Here we studied the impact of IGF2 signaling on protein aggregation in models of Huntington’s disease (HD) as proof-of-concept. Cell culture studies revealed that IGF2 treatment decreases the load of intracellular aggregates of mutant huntingtin and a polyglutamine peptide. These results were validated using induced pluripotent stem cells (iPSC)-derived medium spiny neurons from HD patients. The reduction in the levels of mutant huntingtin was associated with a decrease in the half-life of the intracellular protein. The decrease in the levels of abnormal protein aggregation triggered by IGF2 were independent of the activity of autophagy and the proteasome pathways, the two main routes for mutant huntingtin clearance. Conversely, IGF2 signaling enhanced the secretion of soluble mutant huntingtin species through exosomes and microvesicles involving changes in actin dynamics. Administration of IGF2 into the brain of HD mice using gene therapy led to a significant decrease in the levels of mutant huntingtin in three different animal models. Moreover, analysis of human post-mortem brain tissue, and blood samples from HD patients showed a reduction of IGF2 level. This study identifies IGF2 as a relevant factor deregulated in HD, operating as a disease modifier that buffers the accumulation of abnormal protein aggregates.One sentence summaryIGF2 reduces the load of intracellular protein aggregates through the extracellular disposal of the mutant protein.
Taxallnomy: Closing gaps in the NCBI Taxonomy
Authors: Sakamoto Tetsu , Ortega J. Miguel 
Published: May 2020

ABSTRACTNCBI Taxonomy is the main taxonomic source for several bioinformatics tools and databases since all organisms with sequence accessions deposited on INSDC are organized in its hierarchical structure. Despite the extensive use and application of this data source, taking advantage of its taxonomic tree could be challenging because (1) some taxonomic ranks are missing in some lineages and (2) some nodes in the tree do not have a taxonomic rank assigned (referred to as “no rank”). To address this issue, we developed an algorithm that takes the tree structure from NCBI Taxonomy and generates a hierarchically complete taxonomic tree. The procedures performed by the algorithm consist of attempting to assign a taxonomic rank to “no rank” nodes and of creating/deleting nodes throughout the tree. The algorithm also creates a name for the new nodes by borrowing the names from its ranked child or, if there is no child, from its ranked parent node. The new hierarchical structure was named taxallnomy and it contains 33 hierarchical levels corresponding to the 33 taxonomic ranks currently used in the NCBI Taxonomy database. From taxallnomy, users can obtain the complete taxonomic lineage with 33 nodes of all taxa available in the NCBI Taxonomy database. Taxallnomy is applicable to several bioinformatics analyses that depend on NCBI Taxonomy data. In this work, we demonstrate its applicability by embedding taxonomic information of a specified rank into a phylogenetic tree; and by making metagenomics profiles. Taxallnomy algorithm was written in PERL and all its resources are available atbioinfo.icb.ufmg.br/taxallnomy.Database URL:http://bioinfo.icb.ufmg.br/taxallnomy
The clonal and molecular aetiology of emergency dendritic cell development
Authors: Lin Dawn S. , Tian Luyi , Tomei Sara , Amann-Zalcenstein Daniela , Baldwin Tracey M. , Weber Tom S. , Schreuder Jaring , Stonehouse Olivia , Rautela Jai , Huntington Nicholas D. , Ng Ashley P. , Nutt Stephen L. , Taoudi Samir , Ritchie Matthew E. , Hodgkin Philip D. , Naik Shalin H. 
Published: May 2020

SummaryExtrinsic regulation of single haematopoietic stem and progenitor cell (HSPC) fate is crucial for immune cell development. Here, we examine the aetiology of Flt3 ligand (Flt3L)-mediated emergency development of type 1 conventional dendritic cells (cDC1s), which results in enhanced immunity against infections and cancer. Using cellular barcoding, we demonstrate a predominant role of enhanced clonal expansion and moderate contribution via recruitment of additional cDC1-generating HSPCs. The selective cDC1 expansion occurs primarily via multi-/oligo-potent clones, without compromising output to other lineages. To understand the molecular hallmarks early during a Flt3L response, we developDivi-Seqto simultaneously profile cell division history, surface phenotype and transcriptional state of single HSPCs. We discover that Flt3L-responsive HSPCs maintain a proliferative ‘early progenitor’-like state, which leads to selective emergence of CD11c+cKit+transitional precursors with high cellular output to cDC1s. These findings inform the mechanistic action of Flt3L in natural immunity and immunotherapy at a clonal level.
Transcriptomic response ofCaenorhabditis elegansexpressing human Aβ42gene treated with Salvianolic acid A
Authors: Yuen Chee Wah , Halim Mardani Abdul , Najimudin Nazalan , Azzam Ghows 
Published: May 2020

AbstractAlzheimer’s disease (AD) is a brain disease attributed to the accumulation of extracellular senile plaques comprising β-amyloid peptide (Aβ). In this study, a global transcriptomic analysis of the response of transgenicCaenorhabditis elegansworms expressing full length human Aβ42gene towards Salvianolic acid A (Sal A) was analysed. Antioxidant response genes, namelygst-4,gst-10,spr-1andtrxr-2, were upregulated. The production of Aβ42caused oxidative stress and the antioxidant response genes possibly provide defence to the strain. The gene product oftrxr-2also functionally interacts with the defence system and has a role in life span. Genes involved in replication, reproduction, immune response to microbes and antimicrobial activities were also upregulated. Exposure to Sal A also increased the rate of reproduction of nematodes, and heightened its immunological protection system towards microorganisms. In contrast, genes responsible for locomotion, ligand-gated cation channel, embryonic and postembryonic development, and neuromodulation of chemosensory neurons were significantly down-regulated. As an effector, Sal A might conceivably reduce the movement of the worm by interfering with neuronal transmission and embryonic and post-embryonic development.