bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic characterization of creek sediment microbial communities from a major agricultural region in Salinas, California
Authors: Suttner Brittany J. , Johnston Eric R. , Orellana Luis H. , Rodriguez-R Luis M. , Hatt Janet K. , Carychao Diana , Carter Michelle Q. , Cooley Michael B. , Konstantinidis Konstantinos T. 
Published: August 2019

ABSTRACTLittle is known about the public health risks associated with natural creek sediments that are affected by runoff and fecal pollution from agricultural and livestock practices. For instance, the persistence of foodborne pathogens originating from agricultural activities such as Shiga Toxin-producingE. coli(STEC) in such sediments remains poorly quantified. Towards closing these knowledge gaps, the water-sediment interface of two creeks in the Salinas River Valley was sampled over a nine-month period using metagenomics and traditional culture-based tests for STEC. Our results revealed that these sediment communities are extremely diverse and comparable to the functional and taxonomic diversity observed in soils. With our sequencing effort (~4 Gbp per library), we were unable to detect any pathogenicEscherichia coliin the metagenomes of 11 samples that had tested positive using culture-based methods, apparently due to relatively low pathogen abundance. Further, no significant differences were detected in the abundance of human- or cow-specific gut microbiome sequences compared to upstream, more pristine (control) sites, indicating natural dilution of anthropogenic inputs. Notably, a high baseline level of metagenomic reads encoding antibiotic resistance genes (ARGs) was found in all samples and was significantly higher compared to ARG reads in metagenomes from other environments, suggesting that these communities may be natural reservoirs of ARGs. Overall, our metagenomic results revealed that creek sediments are not a major sink for anthropogenic runoff and the public health risk associated with these sediment microbial communities may be low.IMPORTANCECurrent agricultural and livestock practices contribute to fecal contamination in the environment and the spread of food and water-borne disease and antibiotic resistance genes (ARGs). Traditionally, the level of pollution and risk to public health is assessed by culture-based tests for the intestinal bacterium,E. coli. However, the accuracy of these traditional methods (e.g., low quantification, and false positive signal when PCR-based) and their suitability for sediments remains unclear. We collected sediments for a time series metagenomics study from one of the most highly productive agricultural regions in the U.S. in order to assess how agricultural runoff affects the native microbial communities and if the presence of STEC in sediment samples can be detected directly by sequencing. Our study provided important information on the potential for using metagenomics as a tool for assessment of public health risk in natural environments.
The Signature Microbiota Driving Rumen Function Shifts in Goat Kids Introduced Solid Diet Regimes
Authors: Lv Xiaokang , Chai Jianmin , Diao Qiyu , Huang Wenqin , Zhuang Yimin , Zhang Naifeng 
Published: August 2019

AbstractThe feeding regime of early supplementary solid diet improved rumen development and ruminant production. However, the signature microbiota linking dietary regimes to rumen function shifts and hosts are still unclear. We analyzed the rumen microbiome and functions affected by supplementation of solid diet using a combination of machine learning algorithms. The volatile fatty acids (i.e., acetate, propionate and butyrate) fermented by microbes increased significantly in the supplementary solid diet groups. The predominant genera altered significantly from unclassified Sphingobacteriaceae (non-supplementary group) to Prevotella (supplementary solid diet groups) RandomForest classification model revealed signature microbiota for solid diet that positively correlated with macronutrient intake, and linearly increased with volatile fatty acids production. The nutrient specific bacteria for carbohydrate and protein were also identified. According to FishTaco analysis, a set of intersecting core species contributed with rumen function shifts by solid diet. The core community structures consisted of specific signature microbiota and their symbiotic partners are manipulated by extra nutrients from concentrate and/or forage, and then produce more volatile fatty acids to promote rumen development and functions eventually host development. Our study provides mechanism of microbiome governing by solid diet and highlights the signatures microbiota for animal health and production.ImportanceSmall ruminants are essential protein sources for human, so keeping them health and increasing their production are important. The microbial communities resided in rumen play key roles to convert fiber resources to human food. Moreover, rumen physiology experience huge changes after birth, and understanding its microbiome roles could provide insights for other species. Recently, our studies and others have shown that diet changed rumen microbial composition and goat performance. In this study, we identified core community structures that were affected by diet and associated to the rumen development and goat production. This outcome could potentially allow us to select specific microbiome to improve rumen physiology and functions, maintain host health and benefit animal production. Therefore, it gives a significant clue that core microbiome manipulation by feeding strategies can increase animal products. To our knowledge, we firstly used FishTaco for determination of link between signatures abundances and rumen function shifts.
Analysis of eukaryotic lincRNA sequences reveals signatures of repressed translation in species under strong selection
Authors: Brümmer Anneke , Dreos Rene , Marques Ana Claudia , Bergmann Sven 
Published: August 2019

AbstractLong intergenic non-coding RNAs (lincRNAs) represent a large fraction of transcribed loci in eukaryotic genomes. Although classified as non-coding, most lincRNAs contain open reading frames (ORFs), and it remains unclear why cytoplasmic lincRNAs are not or very inefficiently translated.Here, we analysed signatures of repressed translation in lincRNA sequences from six eukaryotes. In species under stronger selection, i.e. fission yeast and worm, we detected significantly shorter ORFs than in intronic and non-transcribed control regions, a suboptimal sequence context around start codons for translation initiation, and trinucleotides (“codons”) corresponding to less abundant tRNAs than codons in control regions, potentially impeding translation elongation.We verified that varying tRNA expression levels affect ribosome-binding to lincRNAs by analyzing data from five human cell lines. Notably, for three cell lines, codons in abundant cytoplasmic lincRNAs corresponded to lower expressed tRNAs than control codons, substantiating cell type-specific repression of lincRNA translation in human. Finally, comparing non-coding with peptide-encoding ORFs suggested that codon usage at the start of ORFs to be of particular relevance for ribosome-binding.The identified sequence signatures may assist distinguishing peptide- from real non-coding lincRNAs in a cell.
Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction
Authors: Català-Moll Francesc , Weichenhan Dieter , Lutsik Pavlo , Álvarez-Prado Ángel F. , Rodríguez-Ubreva Javier , Klemann Christian , Speckmann Carsten , Abolhassani Hassan , Martínez-Gallo Mónica , Dieli-Crimi Romina , Soler-Palacín Pere , Kracker Sven , Hammarström Lennart , Durandy Anne , Grimbacher Bodo , Plass Christoph , Ballestar Esteban 
Published: August 2019

ABSTRACTMutations in activation induced deaminase (AID) lead to hyper-IgM syndrome type 2 (HIGM2), a rare human primary antibody deficiency. AID-mediated cytosine deamination has been proposed as mediating active demethylation, although evidences both support and cast doubt on such a role. We here made use of HIGM2 B cells to investigate direct AID involvement in active DNA demethylation. HIGM2 naïve and memory B cells both display widespread DNA methylation defects, of which approximately 25% of these defects correspond to active events. For genes that undergo active demethylation that is impaired in HIGM2 individuals, we did not observe AID involvement but a participation of TET enzymes. DNA methylation alterations in HIGM2 naïve B cells are related to premature overstimulation of the B-cell receptor prior to the germinal center reaction. Our data supports a role for AID in B cell central tolerance in preventing the expansion of autoreactive cell clones, affecting the correct establishment of DNA methylation patterns.
Population genomic SNPs from epigenetic RADs: gaining genetic and epigenetic data from a single established next-generation sequencing approach
Authors: Crotti M. , Adams C.E. , Elmer K.R. 
Published: August 2019

SummaryEpigenetics is increasingly recognised as an important molecular mechanism underlying phenotypic variation. To study DNA methylation in ecological and evolutionary contexts, epiRADseq is a cost-effective next-generation sequencing technique based on reduced representation sequencing of genomic regions surrounding non-/methylated sites. EpiRADseq for genome-wide methylation abundance and ddRADseq for genome-wide SNP genotyping follow very similar library and sequencing protocols, but to date these two types of dataset have been handled separately. Here we test the performance of using epiRADseq data to generate SNPs for population genomic analyses.We tested the robustness of using epiRADseq data for population genomics with two independent datasets: a newly generated single-end dataset for the European whitefish Coregonus lavaretus, and a re-analysis of publicly available, previously published paired-end data on corals. Using standard bioinformatic pipelines with a reference genome and without (i.e. de novo catalogue loci), we compared the number of SNPs retained, population genetic summary statistics, and population genetic structure between data drawn from ddRADseq and epiRADseq library preparations.We find that SNPs drawn from epiRADseq are similar in number to those drawn from ddRADseq, with a 55-83% of SNPs being identified by both methods. Genotyping error rate was <5% in both approaches. For summary statistics such as heterozygosity and nucleotide diversity, there is a strong correlation between methods (Spearman’s rho > 0.88). Furthermore, identical patterns of population genetic structure were recovered using SNPs from epiRADseq and ddRADseq approaches.We show that SNPs obtained from epiRADseq are highly similar to those from ddRADseq and are equivalent for estimating genetic diversity and population structure. This finding is particularly relevant to researchers interested in genetics and epigenetics on the same individuals because using a single epigenomic approach to generate two datasets greatly reduces the time and financial costs compared to using these techniques separately. It also efficiently enables correction of epigenetic estimates with population genetic data. Many studies will benefit from a combinatorial approach with genetic and epigenetic markers and this demonstrates a single, efficient method to do so.
A personalised approach for identifying disease-relevant pathways in heterogeneous diseases
Authors: Somani Juhi , Ramchandran Siddharth , Lähdesmäki Harri 
Published: August 2019

AbstractNumerous time-course gene expression datasets have been curated for studying the biological dynamics that drive disease progression; and nearly as many methods have been proposed to analyse them. However, barely any method exists that can appropriately model time-course data and at the same time account for heterogeneity that entails many complex diseases. Most methods manage to fulfil either one of those qualities, but not both. The lack of appropriate methods hinders our capability of understanding the disease process and pursuing preventive or curative treatments. Here, we present a method that models time-course data in a personalised manner, i.e. for each case-control pair individually, using Gaussian processes in order to identify differentially expressed genes (DEGs); and combines the lists of DEGs on a pathway-level using a permutation-based empirical hypothesis testing in order to overcome gene-level variability and inconsistencies prevalent to heterogeneous datasets from complex diseases. Our method can be applied to study the time-course dynamics as well as specific time-windows of heterogeneous diseases. We apply our personalised approach on two longitudinal type 1 diabetes (T1D) datasets to determine perturbations that take place during early prognosis of the disease as well as in time-windows before seroconversion and clinical onset of T1D. By comparing to non-personalised methods, we demonstrate that our approach is biologically motivated and can reveal more insights into progression of heterogeneous diseases. With its robust capabilities of identifying immunologically interesting and disease-relevant pathways, our approach could be useful for predicting certain events in the progression of heterogeneous diseases and even biomarker identification.AvailabilityThe implemented code of our personalised approach will be available online upon publication.
Hingepoints and neural folds reveal conserved features of primary neurulation in the zebrafish forebrain
Authors: Werner Jonathan M. , Negesse Maraki Y. , Brooks Dominique L. , Caldwell Allyson R. , Johnson Jafira M. , Brewster Rachel M. 
Published: August 2019

ABSTRACTPrimary neurulation is the process by which the neural tube, the central nervous system precursor, is formed from the neural plate. Incomplete neural tube closure occurs frequently, yet underlying causes remain poorly understood. Developmental studies in amniotes and amphibians have identified hingepoint and neural fold formation as key morphogenetic events and hallmarks of primary neurulation, the disruption of which causes neural tube defects. In contrast, the mode of neurulation in teleosts such as zebrafish has remained highly debated. Teleosts are thought to have evolved a unique pattern of neurulation, whereby the neural plate infolds in absence of hingepoints and neural folds (NFs), at least in the hindbrain/trunk where it has been studied. We report here on zebrafish forebrain morphogenesis where we identify these morphological landmarks. Our findings reveal a deeper level of conservation of neurulation than previously recognized and establish the zebrafish as a model to understand human neural tube development.
Exploiting epistasis to perturb the evolution of antibiotic resistance
Authors: Lukačišinová Marta , Fernando Booshini , Bollenbach Tobias 
Published: August 2019

AbstractNew ways of curbing the ability of bacteria to evolve spontaneous resistance could mitigate the looming antibiotic resistance crisis. Progress toward this goal requires a comprehensive understanding of the key factors that contribute to resistance evolvability. Here, we present a systematic approach to identify cellular functions that affect the evolvability of resistance. Using a robotic lab-evolution platform that keeps population size and selection pressure under tight control for hundreds ofEscherichia colipopulations evolving in parallel, we quantified the effects of a genome-wide selection of pre-existing gene deletions on resistance evolution. Initial resistance of strains with gene deletions differed by more than tenfold but converged toward a hard upper bound for resistance during the evolution experiment, reflecting a global pattern of diminishing returns epistasis. We identified specific cellular functions that drastically curtail the evolvability of resistance; beyond DNA repair, these include membrane transport, LPS biosynthesis, and chaperones. Perturbations of efflux pumps prevented resistance evolution completely or forced evolution on inferior mutational paths, not explored in the wild type. We show that strong negative epistasis generally underlies these phenomena. The identified functions provide new targets for adjuvants tailored to block evolutionary paths to resistance when combined with antibiotics.
Unexpected differences in the pharmacokinetics of N-acetyl-DL-leucine enantiomers after oral dosing and their clinical relevance
Authors: Churchill Grant C. , Strupp Michael , Galione Antony , Platt Frances M. 
Published: August 2019

AbstractThese results suggest that during chronic administration of the racemate, the D-enantiomer would accumulate, which could have negative effects. The enantiomers of many chiral drugs not only exhibit different pharmacological effects in regard to targets that dictate therapeutic and toxic effects, but are also handled differently in the body due to pharmacokinetic effects. We investigated the pharmacokinetics of the enantiomers of N-acetyl-leucine after administration of the racemate (N-acetyl-DL-leucine) or purified, pharmacologically active L-enantiomer (N-acetyl-L-leucine). Compounds were administered orally to mice. Plasma and tissue samples were collected at predetermined time points (0.25 to 8 h), quantified with liquid chromatography/mass spectrometry, and pharmacokinetic constants were calculated using a noncompartmental model. When administered as the racemate, both the maximum plasma concentration (Cmax) and the area under the plasma drug concentration over time curve (AUC) were much greater for the D-enantiomer relative to the L-enantiomer. When administered as the L-enantiomer, the dose proportionality was greater than unity compared to the racemate, suggesting saturable processes affecting uptake and/or metabolism. Elimination (keand T1/2) was similar for both enantiomers. These results are most readily explained by inhibition of uptake at an intestinal carrier of the L-enantiomer by the D-enantiomer, and by first-pass metabolism of the L-, but not D-enantiomer, likely by deacetylation. In brain and muscle, N-acetyl-L-leucine levels were lower than N-acetyl-D-leucine, consistent with rapid conversion into L-leucine and utilization by normal leucine metabolism. In summary, the enantiomers of N-acetyl-leucine exhibit large, unexpected differences in pharmacokinetics due to both unique handling and/or inhibition of uptake and metabolism of the L-enantiomer by the D-enantiomer. Taken together, these results have clinical implications supporting the use of N-acetyl-L-leucine instead of the racemate or N-acetyl-D-leucine, and support the research and development of isolated N-acetyl-L-leucine.
Cryo-EM structures of α-synuclein fibrils with the H50Q hereditary mutation reveal new polymorphs
Authors: Boyer David R. , Li Binsen , Sun Chuanqi , Fan Weijia , Sawaya Michael R. , Jiang Lin , Eisenberg David S. 
Published: August 2019

AbstractDeposits of amyloid fibrils of α-synuclein are the histological hallmarks of Parkinson’s disease, multiple system atrophy, and dementia with Lewy bodies. Although most cases of these diseases are sporadic, autosomal-dominant hereditary mutations have been linked to Parkinson’s disease and dementia with Lewy bodies. Seeing the changes to the structure of amyloid fibrils bearing these mutations may help to understand these diseases. To this end, we determined the cryo-EM structures of α-synuclein fibrils containing the H50Q hereditary mutation. We find that the H50Q mutation results in two new polymorphs of α-synuclein, which we term Narrow and Wide Fibrils. Both polymorphs recapitulate the conserved kernel formed by residues 50-77 observed in wild-type structures; however, the Narrow and Wide Fibrils reveal that H50Q disrupts a key interaction between H50-E57 on the opposing protofilament, abolishing the extensive protofilament interface formed by preNAC residues in the wild-type “rod” structure. Instead, the Narrow Fibril is formed from a single protofilament and the two protofilaments of the Wide protofilament are held together by only a pair of atoms – the Cɣ atoms from the two threonine 59 sidechains. Further, we find that H50Q forms an intramolecular hydrogen bond with K45 leading to the formation of a novel β-arch formed by residues 36-46 that features an extensive hydrogen-bond network between Y39, T44, and E46. The structures of the H50Q polymorphs help to rationalize the faster aggregation kinetics, higher seeding capacity in biosensor cells, and greater cytotoxicity we observe for H50Q compared to wild-type α-synuclein.
Head Mesoderm Tissue Growth, Dynamics and Neural Crest Cell Migration
Authors: McKinney Mary Cathleen , McLennan Rebecca , Giniunaite Rasa , Baker Ruth E. , Maini Philip K. , Othmer Hans G. , Kulesa Paul M 
Published: August 2019

ABSTRACTVertebrate head morphogenesis involves orchestrated cell growth and tissue movements of the mesoderm and neural crest to form the distinct craniofacial pattern. To better understand structural birth defects, it is important that we learn how these processes are controlled. Here, we examine this question during chick head morphogenesis using time-lapse imaging, computational modeling, and experiment. We find that head mesodermal cells are inherently dynamic in culture and alter cell behaviors in the presence of either ectoderm or neural crest cells. Mesodermal cells in vivo display large-scale whirling motions that rapidly transition to lateral, directed movements after neural crest cells emerge. Computer model simulations predict distinct changes in neural crest migration as the spatio-temporal growth profile of the mesoderm is varied. BrdU-labeling and photoconversion combined with cell density measurements then reveal non-uniform mesoderm growth in space and time. Chemical inhibition of head mesoderm proliferation or ablation of premigratory neural crest alters mesoderm growth and neural crest migration, implying a dynamic feedback between tissue growth and neural crest cell signaling to confer robustness to the system.Summary StatementDynamic feedback between tissue growth and neural crest cell migration ensures robust neural crest stream formation and head morphogenesis shown by time-lapse microscopy, mathematical modeling and embryo perturbations.