bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manual stabilization reveals a transient role for balance control during locomotor adaptation
Authors: Park Sungwoo , Finley James M. 
Published: May 2019

AbstractA fundamental feature of human locomotor control is the need to adapt our walking pattern in response to changes in the environment. For example, when people walk on a split-belt treadmill which has belts that move at different speeds, they adapt to the asymmetric speed constraints by reducing their spatiotemporal asymmetry. Here, we aim to understand the role of stability as a potential factor driving this adaptation process. We recruited 24 healthy, young adults to adapt to walking on a split-belt treadmill while either holding on to a handrail or walking with free arm swing. We measured whole-body angular momentum and step length asymmetry as measures of dynamic balance and spatiotemporal asymmetry, respectively. To understand how changes in intersegmental coordination influenced measures of dynamic balance, we also measured segmental angular momenta and the coefficient of limb cancellation. When participants were initially exposed to the asymmetry in belt speeds, we observed an increase in whole-body angular momentum that was due to both an increase in the momentum of individual limb segments and a reduction in limb cancellation. Holding on to a handrail reduced the perturbation to asymmetry during the early phase of adaptation and resulted in a smaller after-effect during post-adaptation. In addition, the stabilization provided by holding on to a handrail led to reductions in the coupling between angular momentum and asymmetry. These results suggest that regulation of dynamic balance is most important during the initial, transient phase of adaptation to walking on a split-belt treadmill.Summary StatementRegulation of balance exhibits a transient effect on adaptation to imposed asymmetries during bipedal walking. External stabilization attenuates initial deviations in spatiotemporal asymmetry but has no effect on subsequent adaptation.
Consistent metagenome-derived metrics verify and define bacterial species boundaries
Authors: Olm Matthew R. , Crits-Christoph Alexander , Diamond Spencer , Lavy Adi , Matheus Carnevali Paula B. , Banfield Jillian F. 
Published: May 2019

AbstractLongstanding questions relate to the existence of naturally distinct bacterial species and genetic approaches to distinguish them. Bacterial genomes in public databases form distinct groups, but these databases are subject to isolation and deposition biases. We compared 5,203 bacterial genomes from 1,457 environmental metagenomic samples to test for distinct clouds of diversity, and evaluated metrics that could be used to define the species boundary. Bacterial genomes from the human gut, soil, and the ocean all exhibited gaps in whole-genome average nucleotide identities (ANI) near the previously suggested species threshold of 95% ANI. While genome-wide ratios of non-synonymous and synonymous nucleotide differences (dN/dS) decrease until ANI values approach ∼98%, estimates for homologous recombination approached zero at ∼95% ANI, supporting breakdown of recombination due to sequence divergence as a species-forming force. We evaluated 107 genome-based metrics for their ability to distinguish species when full genomes are not recovered. Full length 16S rRNA genes were least useful because they were under-recovered from metagenomes, but many ribosomal proteins displayed both high metagenomic recoverability and species-discrimination power. Taken together, our results verify the existence of sequence-discrete microbial species in metagenome-derived genomes and highlight the usefulness of ribosomal genes for gene-level species discrimination.
Novel Cyclic Peptides in Seed of Annona muricata are Ribosomally Synthesized
Authors: Fisher Mark F. , Zhang Jingjing , Berkowitz Oliver , Whelan James , Mylne Joshua S. 
Published: May 2019

ABSTRACTSmall, cyclic peptides are reported to have many bioactivities. In bacteria and fungi they can be made by non-ribosomal peptide synthetases, but in plants they are exclusively ribosomal. Cyclic peptides from the Annona genus possess cytotoxic and anti-inflammatory activities, but their biosynthesis is unknown. The medicinal soursop plant, Annona muricata, contains annomuricatins A (cyclo-PGFVSA) and B (cyclo-PNAWLGT). Here, using de novo transcriptomics and tandem mass spectrometry, we identify a suite of short transcripts for precursor proteins for ten validated annomuricatins, nine of which are novel. In their precursors, annomuricatins are preceded by an absolutely conserved Glu and each peptide sequence has a conserved proto-C-terminal Pro, revealing parallels with the segetalin orbitides from the seed of Vaccaria hispanica, which are processed through ligation by a prolyl oligopeptidase in a transpeptidation reaction.
A role for Toxoplasma gondii chloroquine resistance transporter in bradyzoite viability and digestive vacuole maintenance
Authors: Kannan Geetha , Di Cristina Manlio , Schultz Aric J. , Huynh My-Hang , Wang Fengrong , Schultz Tracey L. , Lunghi Matteo , Coppens Isabelle , Carruthers Vern B. 
Published: May 2019

ABSTRACTToxoplasma gondii is a ubiquitous pathogen that can cause encephalitis, congenital defects, and ocular disease. T. gondii has also been implicated as a risk factor for mental illness in humans. The parasite persists in the brain as slow growing bradyzoites contained within intracellular cysts. No treatments exist to eliminate this form of parasite. Although proteolytic degradation within the parasite lysosomal-like vacuolar compartment (VAC) is critical for bradyzoite viability, whether other aspects of the VAC are important for parasite persistence remains unknown. An ortholog of Plasmodium falciparum CRT has previously been identified in T. gondii (TgCRT). To interrogate the function of TgCRT in chronic stage bradyzoites and its role in persistence, we knocked out TgCRT in a cystogenic strain and assessed VAC size, VAC digestion of host-derived proteins and parasite autophagosomes, and viability of in vitro and in vivo bradyzoites. We found that whereas parasites deficient in TgCRT exhibit normal digestion within the VAC, they display a markedly distended VAC and their viability is compromised both in vitro and in vivo. Interestingly, impairing VAC proteolysis in TgCRT deficient bradyzoites restored VAC size, consistent with a role for TgCRT as a transporter of products of digestion from the VAC. In conjunction with earlier studies, our current findings suggest a functional link between TgCRT and VAC proteolysis. This work provides further evidence of a crucial role for the VAC in bradyzoite persistence and a new potential VAC target to abate chronic Toxoplasma infection.IMPORTANCEIndividuals chronically infected with the intracellular parasite Toxoplasma gondii are at risk of experiencing reactivated disease that can result in progressive loss of vision. No effective treatments exist for chronic toxoplasmosis due in part to a poor understanding of the biology underlying chronic infection and a lack of well validated potential targets. Here we show that a T. gondii transporter is functionally linked to protein digestion within the parasite lysosome-like organelle and that this transporter is necessary to sustain chronic infection in culture and in experimentally infected mice. Ablating the transporter results in severe bloating of the lysosome-like organelle. Together with earlier work, this study suggests the parasite’s lysosome-like organelle is vital for parasite survival, thus rendering it a potential target for diminishing infection and reducing the risk of reactivated disease.
Microbial composition of the human nasopharynx varies according to influenza virus type and vaccination status
Authors: Ding Tao , Song Timothy , Zhou Bin , Geber Adam , Ma Yixuan , Zhang Lingdi , Volk Michelle , Kapadia Shashi N. , Jenkins Stephen G. , Salvatore Mirella , Ghedin Elodie 
Published: May 2019

AbstractFactors that contribute to enhanced susceptibility to severe bacterial disease after influenza infection are not well defined, but likely include the microbiome of the respiratory tract. Vaccination against influenza, while having variable effectiveness, could also play a role in microbial community stability. We collected nasopharyngeal samples from 215 individuals infected with influenza A/H3N2 or influenza B and profiled the microbiota by target sequencing of the 16S rRNA gene. We identified signature taxonomic groups by performing linear discriminant analysis and effective size comparisons (LEfSe) and defined bacterial community types using Dirichlet Multinomial Mixture (DMM) models. Influenza infection was shown to be significantly associated with microbial composition of the nasopharynx according to the virus type and the vaccination status of the patient. We identified 4 microbial community types across the combined cohort of influenza patients and healthy individuals with one community type most representative of the influenza-infected group. We also identified microbial taxa for which relative abundance was significantly higher in the unvaccinated elderly group; these taxa include species known to be associated with pneumonia.ImportanceOur results suggest that there is a significant association between the composition of the microbiota in the nasopharynx and the influenza virus type causing the infection. We observe that vaccination status, especially in more senior individuals, also has an association with the microbial community profile. This indicates that vaccination against influenza, even when ineffective to prevent disease, could play a role in controlling secondary bacterial complications.
Revealing The Colourful Side of Birds: Spatial Distribution of Conspicuous Plumage Colours on The Body of Australian Birds
Authors: Delhey Kaspar 
Published: May 2019

ABSTRACTIn many species of birds, different body parts often display very different colours. This spatial distribution of coloured plumage patches may be determined by the balance between being cryptic to predators, and conspicuous to intended receivers. If this is the case, ventral and anterior body parts in birds–which are less visible to predators but more prominent to conspecifics– should present more conspicuous and sexually dichromatic plumage colours. Here I test these predictions using reflectance spectrometric measurements of standardised plumage patches across males and females for nearly an entire avifauna (Australian landbirds, N = 538 species). My data show that, as predicted, conspicuous colours are mainly located near the head, while the plumage of the back is the most cryptic. However, there is considerable variation across species, and this makes position on the body a relatively modest predictor of plumage elaboration (R2= 0.15-0.19). One clear exception to this pattern is the conspicuous rump coloration. In many species, this patch can be concealed by wings, and therefore exposed only when necessary. In addition, conspicuous rump coloration could deflect or confuse predators in case of attack. Finally, patterns for sexual dichromatism were much weaker (R2= 0.02), whereby wing and tail showed lower levels of dichromatism than the rest of the body.
Source-Sink Modifications Affect Leaf Senescence and Grain Mass in Wheat
Authors: Lv Xuemei , Zhang Yan , Zhang Yunxiu , Fan Shoujin , Kong Lingan 
Published: May 2019

AbstractA field experiment was performed in wheat to investigate the responses of flag leaf and grain to sink/source manipulations. The results showed that half-degraining delayed but defoliation (only flag leaf left) enhanced the leaf senescence. Sink/source manipulations influenced the content of reactive oxygen species of flag leaf and the content of phytohormones including cytokinins, indoleacetic 3-acid, gibberellin 3, salicylic acid and jasmonic acid in the defoliated flag leaf (DL) and grain (DG), half-degrained flag leaf (HL) and grain (HG). An iTRAQ based quantitative proteomic analysis indicated that at 16 days after manipulation a total of 97 and 59 differentially expressed proteins (DEPs) from various functional categories were observed in HL and DL groups, respectively, compared with control and 115 and 121 DEPs were observed in HG and DG groups, respectively. GO annotation terms of DEPs mainly included carbon fixation, hydrogen peroxide catabolic process, chloroplast and cytoplasm, oxidoreductase activity and glutamate synthase activity in flag leaf of manipulated plants; organonitrogen compound metabolic process, cytoplasm, vacuolar membrane, CoA carboxylase activity, starch synthase activity and nutrient reservoir activity in grain of manipulated plants. KEGG pathway enrichment analysis revealed that photosynthesis, carbon, nitrogen and pyruvate metabolisms and glycolysis/gluconeogenesis were the most remarkable processes for sink/source manipulations. Sink/source manipulations affected the activities of α- and β- amylases and proteinases. Ultimately, manipulations changed the mass per grain. In conclusion, manipulations to change the sink/source ratio affect the levels of hormones, activities of hydrolytic enzymes, metabolisms of carbon, nitrogen and other main compounds, stress resistance, the leaf senescence, and ultimately influence the grain mass.
Design principles of ROS dynamic networks relevant to precision therapies for age-related diseases
Authors: Kolodkin Alexey , Sharma Raju Prasad , Colangelo Anna Maria , Ignatenko Andrew , Martorana Francesca , Jennen Danyel , Briede Jacco J. , Brady Nathan , Barberis Matteo , Mondeel Thierry D.G.A. , Papa Michele , Kumar Vikas , Peters Bernhard , Skupin Alexander , Alberghina Lilia , Balling Rudi , Westerhoff Hans V. 
Published: May 2019

AbstractThe eminently complex regulatory network protecting the cell against oxidative stress, surfaces in several disease maps, including that of Parkinson’s disease (PD). How this molecular networking achieves its various functionalities and how processes operating at the seconds-minutes time scale cause a disease at a time scale of multiple decennia is enigmatic.By computational analysis, we here disentangle the reactive oxygen species (ROS) regulatory network into a hierarchy of subnetworks that each correspond to a different functionality. The detailed dynamic model of ROS management obtained integrates these functionalities and fitsin vitrodata sets from two different laboratories.The model shows effective ROS-management for a century, followed by a sudden system’s collapse due to the loss of p62 protein. PD related conditions such as lack of DJ-1 protein or increased α-synuclein accelerated the system’s collapse. Variousin-silicointerventions (e.g. addition of antioxidants or caffeine) slowed down the collapse of the systemin silico, suggesting the model may help discover new medicinal and nutritional therapies.
Direct Measurement of Synchronous Precursor Selection (SPS) Accuracy in Public Proteomics Datasets
Authors: Jenkins Conor , Rinas Aimee , Orsburn Ben 
Published: May 2019

AbstractReporter ion quantification techniques utilizing reagents such as TMT and iTRAQ allow proteomics studies to multiplex up to 11 different samples within a single LC-MS/MS experimental run. In these experiments, peptides derived from different samples are labeled with chemical tags possessing identical mass but differing distributions of heavy isotopes through their structure. Peptides from all samples may then be physically combined prior to LC-MS/MS. Relative quantification of the peptides from each sample is obtained from the liberation of low mass reporter ions alone, as these are the only discernible factor between peptides in the entire LC-MS/MS workflow. When coeluting ions of similar mass to charge ratios are fragmented along with the ions of interest, it is not possible to determine the source of the reporter fragments and quantification is skewed, most often resulting in ratio suppression. One technique for combatting ratio suppression is the selection of MS2 fragment ions that are likely to retain the intact mass tag region by synchronous precursor selection (SPS) and the liberation of the reporter ions from this combination of ions in MS/MS/MS (MS3). In this study we utilize a new post processing tool that can directly assess the accuracy of the SPS system for picking ions for quantification that are truly derived from the peptide of interest. We then apply this tool to the re-analysis of 3 public proteomics datasets. Directly assessing SPS accuracy allows a new measurement of confidence in the quantification values obtained from these reporter ion quantification experiments.Abstract Graphic
EpiScanpy: integrated single-cell epigenomic analysis
Authors: Danese Anna , Richter Maria L. , Fischer David S. , Theis Fabian J. , Colomé-Tatché Maria 
Published: May 2019

ABSTRACTEpigenetic single-cell measurements reveal a layer of regulatory information not accessible to single-cell transcriptomics, however single-cell-omics analysis tools mainly focus on gene expression data. To address this issue, we present epiScanpy, a computational framework for the analysis of single-cell DNA methylation and single-cell ATAC-seq data. EpiScanpy makes the many existing RNA-seq workflows from scanpy available to large-scale single-cell data from other -omics modalities. We introduce and compare multiple feature space constructions for epigenetic data and show the feasibility of common clustering, dimension reduction and trajectory learning techniques. We benchmark epiScanpy by interrogating different single-cell brain mouse atlases of DNA methylation, ATAC-seq and transcriptomics. We find that differentially methylated and differentially open markers between cell clusters enrich transcriptome-based cell type labels by orthogonal epigenetic information.
Uncovering bi-directional causal relationships between plasma proteins and psychiatric disorders: A proteome-wide study and directed network analysis
Authors: Chau Carlos Kwan-long , Lau Alexandria , Sham Pak-Chung , So Hon-Cheong 
Published: May 2019

AbstractPsychiatric disorders represent a major public health burden yet their etiologies remain poorly understood, and treatment advances are limited. In addition, there are no reliable biomarkers for diagnosis or progress monitoring.Here we performed a proteome-wide causal association study covering 3522 plasma proteins and 24 psychiatric traits or disorders, based on large-scale GWAS data and the principle of Mendelian randomization (MR). We have conducted ~95,000 MR analyses in total; to our knowledge, this is the most comprehensive study on the causal relationship between plasma proteins and psychiatric traits.The analysis was bi-directional: we studied how proteins may affect psychiatric disorder risks, but also looked into how psychiatric traits/disorders may be causal risk factors for changes in protein levels. We also performed a variety of additional analysis to prioritize protein-disease associations, including HEIDI test for distinguishing functional association from linkage, analysis restricted to cis- acting variants and replications in independent datasets from the UK Biobank. Based on the MR results, we constructed directed networks linking proteins, drugs and different psychiatric traits, hence shedding light on their complex relationships and drug repositioning opportunities. Interestingly, many top proteins were related to inflammation or immune functioning. The full results were also made available online in searchable databases.In conclusion, identifying proteins causal to disease development have important implications on drug discovery or repurposing. Findings from this study may also guide the development of blood-based biomarkers for the prediction or diagnosis of psychiatric disorders, as well as assessment of disease progression or recovery.
Widespread microbial mercury methylation genes in the global ocean
Authors: Villar Emilie , Cabrol Lea , Heimbürger-Boavida Lars-Eric 
Published: May 2019

AbstractMethylmercury is a neurotoxin that bioaccumulates from seawater to high concentrations in marine fish, putting human and ecosystem health at risk. High methylmercury levels have been found in the oxic subsurface waters of all oceans, yet only anaerobic microorganisms have been identified so far as efficient methylmercury producers in anoxic environments. The microaerophilic nitrite oxidizing bacteriaNitrospinahas been previously suggested as a possible mercury methylator in Antarctic sea ice. However, the microorganisms processing inorganic mercury into methylmercury in oxic seawater remain unknown. Here we show metagenomic evidence from open ocean for widespread microbial methylmercury production in oxic subsurface waters. We find high abundances of the key mercury methylating geneshgcABacross all oceans corresponding to taxonomic relatives of known mercury methylators from Deltaproteobacteria, Firmicutes and Chloroflexi. Our results identifyNitrospinaas the predominant and widespread key player for methylmercury production in the oxic subsurface waters of the global ocean.
Antibody cross-reactivity accounts for widespread appearance of m1A in 5’ UTRs
Authors: Grozhik Anya V. , Olarerin-George Anthony O. , Sindelar Miriam , Li Xing , Gross Steven S. , Jaffrey Samie R. 
Published: May 2019

AbstractN1-methyladenosine (m1A) was recently identified as a new mRNA modification based on its mapping to the 5’ UTRs of thousands of mRNAs with an m1A-binding antibody. More recent studies have confirmed the prevalence of m1A, while others have questioned it. To address this discrepancy, we mapped m1A using ultra-deep RNA-Seq datasets based on m1A-induced misincorporations during reverse transcription. Using this approach, we find m1A only in the mitochondrial MT-ND5 transcript. In contrast, when we mapped m1A antibody-binding sites at single-nucleotide resolution, we found binding to transcription start nucleotides in mRNA 5’ UTRs. Using different biochemical assays, we find that m1A is not present at these sites. Instead, we find that the m1A antibody exhibits m1A-independent binding to mRNA cap structures. We also tested a new and independently derived m1A antibody. We show that this m1A antibody lacks m7G cap-binding cross-reactivity, and notably does not map to 5’ UTRs in the transcriptome. Our data demonstrate that high-stoichiometry m1A sites are rare in the transcriptome and that previous mapping of m1A to mRNA 5’ UTRs are due to unintended binding of the m1A antibody to m7G cap structure in mRNA.