bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effector Gene Reshuffling Involves Dispensable Mini-chromosomes in the Wheat Blast Fungus
Authors: Peng Zhao , Garcia Ely Oliveira , Lin Guifang , Hu Ying , Dalby Melinda , Migeon Pierre , Tang Haibao , Farman Mark , Cook David , White Frank F. , Valent Barbara , Liu Sanzhen 
Published: June 2018

AbstractNewly emerged wheat blast disease is a serious threat to global wheat production. Wheat blast is caused by a distinct, exceptionally diverse lineage of the fungus causing rice blast disease. To understand genetic diversity in wheat-infecting strains, we report a near-finished reference genome of a recent field isolate generated using long read sequencing and a novel scaffolding approach with long-distance paired genomic sequences. The genome assemblage includes seven core chromosomes and sequences from a dispensable mini-chromosome that harbors effector genes normally found on the ends of core chromosomes in other strains. No mini-chromosomes were observed in an early field strain, and two mini-chromosomes from another field isolate each contain different effector homologous genes and core chromosome end sequences. The mini-chromosome is highly repetitive and is enriched in transposons occurring most frequently at core chromosome ends. Additionally, transposons in mini-chromosomes lack the characteristic signature for inactivation by repeat-induced point (RIP) mutation genome defenses. Our results, collectively, indicate that dispensable mini-chromosomes and non-dispensable core chromosomes undergo divergent evolutionary trajectories, and mini-chromosomes and core chromosome ends are coupled as a mobile, fast-evolving effector compartment in the wheat pathogen genome.Significance statementThe emerging blast disease on wheat is proving even harder to control than the ancient, still-problematic rice blast disease. Potential wheat resistance identified using strains isolated soon after disease emergence are no longer effective in controlling recent aggressive field isolates from wheat in South America and South Asia. We report that recent wheat pathogens can contain one or two highly-variable conditionally-dispensable mini-chromosomes, each with an amalgamation of effector sequences that are duplicated or absent from pathogen core chromosome ends. Well-studied effectors found on different core chromosomes in rice pathogens appear side-by-side in wheat pathogen mini-chromosomes. The rice pathogen often overcomes deployed resistance genes by deleting triggering effector genes. Localization of effectors on mini-chromosomes, which are unstably transmitted during growth, would accelerate pathogen adaptation in the field.
Beyond type 1 regulatory T cells: co-expression of LAG3 and CD49b in IL-10-producing T cell lineages
Authors: Huang Weishan , Solouki Sabrina , Carter Chavez , Zheng Song-Guo , August Avery 
Published: June 2018

ABSTRACTType 1 regulatory CD4+T (Tr1) cells express high levels of the immunosuppressive cytokine IL-10 but not the master transcription factor Foxp3, and can suppress inflammation and promote immune tolerance. In order to identify and obtain viable Tr1 cells for research and clinical applications, co-expression of CD49b and LAG3 has been proposed as a unique surface signature for both human and mouse Tr1 cells. However, recent studies have revealed that this pattern of co-expression is dependent on the stimulating conditions and the differentiation stage of the CD4+T cells. Here, using an IL-10GFP/Foxp3RFPdual reporter transgenic murine model, we demonstrate that co-expression of CD49b and LAG3 is not restricted to the Foxp3−Tr1 cells, but is also observed in Foxp3+T regulatory (Treg) cells and CD8+T cells that produce IL-10. Our data indicate that IL-10-producing Tr1 cells, Treg cells and CD8+T cells are all capable of co-expressing LAG3 and CD49bin vitrofollowing differentiation under IL-10-inducing conditions, andin vivofollowing pathogenic insult or infection in the pulmonary mucosa. Our findings urge caution in the use of LAG3/CD49b co-expression to identify Tr1 cells, since it may mark IL-10-producing T cell lineages more broadly, including the Foxp3−Tr1 cells, Foxp3+Treg cells and CD8+T cells.
Optimizing guide RNA selection and CRISPR/Cas9 methodology for efficient generation of deletions in C. elegans
Authors: Au Vinci , Li-Leger Erica , Raymant Greta , Flibotte Stephane , Chen George , Martin Kiana , Fernando Lisa , Doell Claudia , Rosell Federico I. , Wang Su , Edgley Mark L. , Rougvie Ann E. , Hutter Harald , Moerman Donald G. 
Published: June 2018

AbstractThe Caenorhabditis elegans Gene Knockout (KO) Consortium is tasked with obtaining null mutations in each of the more than 20,000 open reading frames (ORFs) of this organism. To date, approximately15,000 ORFs have associated putative null alleles. A directed approach using CRISPR/Cas9 methodology is the most promising technique to complete the task. While there has been substantial success in using CRISPR/Cas9 in C. elegans, there has been little emphasis on optimizing the method for generating large insertions/deletions in this organism. To enhance the efficiency of using CRISPR/Cas9 to generate gene knockouts in C. elegans we have developed an online species-specific guide RNA selection tool (http://genome.sfu.ca/crispr). When coupled with previously developed selection vectors, optimization for homology arm length, and the use of purified Cas9 protein, we demonstrate a robust, efficient and effective protocol for generating deletions. Debate and speculation in the larger scientific community about off- target effects due to non-specific Cas9 cutting has prompted us to investigate through whole genome sequencing the occurrence of single nucleotide variants and indels accompanying targeted deletions. We did not detect any off-site variants above the natural spontaneous mutation rate and therefore conclude this modified protocol does not generate off-target events to any significant degree in C. elegans.
NovelexcGenes Involved in Formation of the Tubular Excretory Canals ofC. elegans
Authors: Al-Hashimi Hikmat , Chiarelli Travis , Lundquist Erik A. , Buechner Matthew 
Published: June 2018

ABSTRACTRegulation of luminal diameter is critical to the function of small single-celled tubes, of which the seamless tubular excretory canals ofC. elegansprovide a tractable genetic model. Mutations in several sets of genes exhibit the Exc phenotype, in which canal luminal growth is visibly altered. Here, a focused reverse genomic screen of genes highly expressed in the canals found 24 genes that significantly affect luminal outgrowth or diameter. These genes encode novel proteins as well as highly conserved proteins involved in processes including gene expression, cytoskeletal regulation, vesicular movement, and transmembrane transport. In addition, two genes act as suppressors on a pathway of conserved genes whose products mediate vesicle movement from early to recycling endosomes. The results provide new tools for understanding the integration of cytoplasmic structure and physiology in forming and maintaining the narrow diameter of single-cell tubules.
Deconvolution of substrate processing by the 26S proteasome reveals a selective kinetic gateway to degradation
Authors: Bard J.A.M. , Bashore C. , Dong K.C. , Martin A. 
Published: June 2018

AbstractThe 26S proteasome is the principle macromolecular machine responsible for protein degradation in eukaryotes. However, little is known about the detailed kinetics and coordination of the underlying substrate-processing steps of the proteasome, and their correlation with observed conformational states. Here, we used reconstituted 26S proteasomes with unnatural amino acid-attached fluorophores in a series of FRET and anisotropy-based assays to probe substrate-proteasome interactions, the individual steps of the processing pathway, and the conformational state of the proteasome itself. We develop a complete kinetic picture of proteasomal degradation, which reveals that the engagement steps prior to substrate commitment are fast relative to subsequent deubiquitination, translocation and unfolding. Furthermore, we find that non-ideal substrates are rapidly rejected by the proteasome, which thus employs a kinetic proofreading mechanism to ensure degradation fidelity and substrate prioritization.
Human salivary amylase gene copy number impacts oral and gut microbiomes
Authors: Poole Angela C. , Goodrich Julia K. , Youngblut Nicholas D. , Luque Guillermo G. , Ruaud Albane , Sutter Jessica L. , Waters Jillian L. , Shi Qiaojuan , El-Hadidi Mohamed , Johnson Lynn M. , Bar Haim Y. , Huson Daniel H. , Booth James G. , Ley Ruth E. 
Published: June 2018

SummaryHost genetic variation influences the composition of the human microbiome. While studies have focused on associations between the microbiome and single nucleotide polymorphisms in genes, their copy number (CN) can also vary. Here, in a study of human subjects including a 2-week standard diet, we relate oral and gut microbiome to CN at theAMY1locus, which encodes the gene for salivary amylase, active in starch degradation. We show that although diet standardization drove gut microbiome convergence,AMY1-CN influenced oral and gut microbiome composition and function. The gut microbiomes of low-AMY1-CN subjects had an enhanced capacity for breakdown of complex carbohydrates. Those of high-AMY1subjects were enriched in microbiota linked to resistant starch fermentation, had higher fecal SCFAs, and drove higher adiposity when transferred to germfree mice. Gut microbiota results were validated in a larger separate population. This study establishesAMY1-CN as a genetic factor patterning microbiome composition and function.
Comparative Biochemical and Structural Analysis of Novel Cellulose Binding Proteins (Tāpirins) from Extremely Thermophilic Caldicellulosiruptor Species
Authors: Lee Laura L. , Hart William S. , Lunin Vladimir V. , Alahuhta Markus , Bomble Yannick J. , Himmel Michael E. , Blumer-Schuette Sara E. , Adams Michael W.W. , Kelly Robert M. 
Published: June 2018

AbstractGenomes of extremely thermophilic Caldicellulosiruptor species encode novel cellulose binding proteins, tāpirins, located proximate to the type IV pilus locus. Previously, the C-terminal domain of a tāpirin (Calkro_0844) from Caldicellulosiruptor kronotskyensis was shown to be structurally unique and have a cellulose binding affinity akin to family 3 carbohydrate binding modules (CBM3). Here, full-length and C-terminal versions of tāpirins from Caldicellulosiruptor bescii (Athe_1870), Caldicellulosiruptor hydrothermalis (Calhy_0908), Caldicellulosiruptor kristjanssonii (Calkr_0826), and Caldicellulosiruptor naganoensis (NA10_0869) were produced recombinantly in Escherichia coli and compared to Calkro_0844. All five tāpirins bound to microcrystalline cellulose, switchgrass, poplar, filter paper, but not to xylan. Densitometry analysis of bound protein fractions visualized by SDS-PAGE revealed that Calhy_0908 and Calkr_0826 (from weakly cellulolytic species) associated with the cellulose substrates to a greater extent than Athe_1870, Calkro_0844 and NA10_0869 (from strongly cellulolytic species), perhaps to associate closely with biomass to capture glucans released from lignocellulose by cellulases produced in Caldicellulosiruptor communities. Three-dimensional structures of the C-terminal binding regions of Calhy_0908 and Calkr_0826 were closely related to Calkro_0844, despite the fact that their amino acid sequence identities compared to Calkro_0844 were only 16% and 36%, respectively. Unlike the parent strain, C. bescii mutants lacking the tāpirin genes did not bind to cellulose following short-term incubation, reinforcing the significance of these proteins in cell association with plant biomass. Given the scarcity of carbohydrates in neutral terrestrial hot springs, tāpirins likely help cells scavenge carbohydrates from lignocellulose to support growth and survival of Caldicellulosiruptor species.ImportanceMechanisms by which microorganisms attach to and degrade lignocellulose are important to understand if effective approaches for conversion of plant biomass into fuels and chemicals are to be developed. Caldicellulosiruptor species grow on carbohydrates from lignocellulose at elevated temperatures and have biotechnological significance for that reason. Novel cellulose binding proteins, called tāpirins, are involved in the way Caldicellulosiruptor species interact with microcrystalline cellulose and here additional information about the diversity of these proteins across the genus is provided, including three dimensional structural comparisons.
Mutation-driven evolution of Pseudomonas aeruginosa in the presence of either ceftazidime or ceftazidime/avibactam
Authors: Sanz-García Fernando , Hernando-Amado Sara , Martínez José Luis 
Published: June 2018

ABSTRACTCeftazidime/avibactam is a combination of beta-lactam/beta-lactamases inhibitor, which use is restricted to some clinical cases including cystic fibrosis patients infected with multidrug resistant Pseudomonas aeruginosa, in which mutation is the main driver of resistance. This study aims to predict the mechanisms of mutation-driven resistance that are selected for when P. aeruginosa is challenged with either ceftazidime or ceftazidime/avibactam. For this purpose, P. aeruginosa PA14 was submitted to experimental evolution in the absence of antibiotics and in the presence of increasing concentrations of ceftazidime or ceftazidime/avibactam for 30 consecutive days. Final populations were analysed by whole-genome sequencing. All evolved populations reached similar levels of ceftazidime resistance. Besides, all of them were more susceptible to amikacin and produced pyomelanin. A first event in the evolution was the selection of large chromosomal deletions containing hmgA (involved in pyomelanin production), galU (involved in β-lactams resistance) and mexXY-oprM (involved in aminoglycoside resistance). Besides mutations in mpl and dacB that regulate β-lactamase expression, mutations related to MexAB-OprM overexpression were prevalent. Ceftazidime/avibactam challenge selected mutants in the putative efflux pump PA14_45890-45910 and in a two-component system (PA14_45870-45880), likely regulating its expression. All populations produce pyomelanin and were more susceptible to aminoglycosides likely due to the selection of large chromosomal deletions. Since pyomelanin-producing mutants, presenting similar deletions are regularly isolated from infections, the potential aminoglycosides hyper-susceptiblity and reduced β-lactams susceptibility of pyomelanin-producing P. aeruginosa should be taken into consideration for treating infections by these isolates.
The transfer function of the rhesus macaque oculomotor system for small-amplitude slow motion trajectories
Authors: Skinner Julianne , Buonocore Antimo , Hafed Ziad M. 
Published: June 2018

AbstractTwo main types of small eye movements occur during gaze fixation: microsaccades and slow ocular drifts. While microsaccade generation has been relatively well-studied, ocular drift control mechanisms are unknown. Here we explored the degree to which monkey smooth eye movements, on the velocity scale of slow ocular drifts, can be generated systematically. Two male rhesus macaque monkeys tracked a spot moving sinusoidally, but slowly, along the horizontal or vertical directions. Maximum target displacement in the motion trajectory was 30 min arc (0.5 deg), and we varied the temporal frequency of target motion from 0.2 to 5 Hz. We obtained an oculomotor “transfer function” by measuring smooth eye velocity gain (relative to target velocity) as a function of frequency, similar to past work with large-amplitude pursuit. Monkey eye velocities as slow as those observed during slow ocular drifts were clearly target-motion driven. Moreover, like with large-amplitude smooth pursuit, eye velocity gain varied with temporal frequency. However, unlike with large-amplitude pursuit, exhibiting low-pass behavior, small-amplitude motion tracking was band-pass with the best ocular movement gain occurring at ~0.8-1 Hz. When oblique directions were tested, we found that the horizontal component of pursuit gain was larger than the vertical component. Our results provide a catalogue of the control abilities of the monkey oculomotor system for slow target motions, and they also support the notion that smooth fixational ocular drifts are controllable. This has implications for neural investigations of drift control and the image-motion consequences of drifts on visual coding in early visual areas.
Associations between plant and pollinator communities under grassland restoration respond mainly to landscape connectivity
Authors: Rotchés‐Ribalta Roser , Winsa Marie , Roberts Stuart P. M. , Öckinger Erik 
Published: June 2018

Abstract

Land‐use change can disrupt associations between different trophic groups, but it is unclear if habitat restoration can recover these associations. In Sweden, restoration efforts have been applied to increase areas of semi‐natural grassland previously remaining as small fragments due to abandonment. We assessed how the associations between plant and pollinator communities can be modified by grassland abandonment and restoration, together with landscape connectivity.

We surveyed plant, hoverfly and bee communities in 10 abandoned, 18 restored and 10 intact grasslands in south‐central Sweden, distributed along a gradient of isolation from other species‐rich grasslands. We assessed the effects of management history and connectivity on the relationships between several measures of the composition of plant and pollinator communities as well as between plant community composition and pollinator guilds.

The composition of the local flowering plant community was an important determinant of both hoverfly and bee communities. However, plant‐pollinator associations were modulated by landscape connectivity and, to some extent, by grassland management history. Abundance, species richness and functional richness of bees and species richness of hoverflies were positively associated with local plant communities in isolated grasslands, but these associations weakened in well‐connected grasslands. In contrast, hoverfly abundance correlated positively with plant communities in well‐connected grasslands.

The response of pollinator feeding guilds was consistent with overall pollinator communities. However, abundance of bees adapted to foraging on particular plants (long‐tongued and short‐tongued) responded positively to specific host plant species abundance.

Synthesis and applications. Our results show how land use and landscape context can significantly affect interactions between different trophic levels. Land use and landscape context should therefore be recognised in grassland restoration guidelines. Enhancement of both functional‐rich and species‐rich plant communities, as well as increasing abundance and species and functional richness of host plants for specialist pollinators will amend pollinator diversity. Restoration actions should consider the spatial configuration of the landscape to improve its outcome. Efforts in more isolated grasslands should focus on promoting local habitat quality while, in more connected grasslands, the priority should be maintaining connectivity to well‐preserved grasslands.
Border Effects in House Prices
Authors: Micheli Martin , Rouwendal Jan , Dekkers Jasper 
Published: June 2018

AbstractThis article estimates the effect of the Dutch–German border on house prices. We argue that the difference between house prices at the border indicates the willingness to pay to stay in a country compared to living across the border. After a change in the tax rules in 2001, migration from the Netherlands to Germany increased substantially and the gradient of Dutch house price towards the German border steepened. Combining a German and Dutch real estate dataset and using different estimation strategies, we find that asking prices of comparable housing drop by about 16% when one crosses the Dutch–German border.
Gene expression‐based drug repurposing to target aging
Authors: Dönertaş Handan Melike , Fuentealba Valenzuela Matías , Partridge Linda , Thornton Janet M. 
Published: June 2018

AbstractAging is the largest risk factor for a variety of noncommunicable diseases. Model organism studies have shown that genetic and chemical perturbations can extend both lifespan and healthspan. Aging is a complex process, with parallel and interacting mechanisms contributing to its aetiology, posing a challenge for the discovery of new pharmacological candidates to ameliorate its effects. In this study, instead of a target‐centric approach, we adopt a systems level drug repurposing methodology to discover drugs that could combat aging in human brain. Using multiple gene expression data sets from brain tissue, taken from patients of different ages, we first identified the expression changes that characterize aging. Then, we compared these changes in gene expression with drug‐perturbed expression profiles in the Connectivity Map. We thus identified 24 drugs with significantly associated changes. Some of these drugs may function as antiaging drugs by reversing the detrimental changes that occur during aging, others by mimicking the cellular defence mechanisms. The drugs that we identified included significant number of already identified prolongevity drugs, indicating that the method can discover de novo drugs that meliorate aging. The approach has the advantages that using data from human brain aging data, it focuses on processes relevant in human aging and that it is unbiased, making it possible to discover new targets for aging studies.
Stabilization treatment of remitted psychotic depression: the STOP‐PD study
Authors: Bingham K. S. , Meyers B. S. , Mulsant B. H. , Rothschild A. J. , Whyte E. M. , Banerjee S. , Artis A. S. , Alexopoulos G. S. , Flint A. J. ,   the STOP‐PD Study Group
Published: June 2018

ObjectiveWe conducted a 12‐week double‐blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD).MethodsSeventy‐one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double‐blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination.ResultsThe effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12‐week stabilization phase; the remaining metabolic measures did not significantly change.ConclusionContinuation of acute treatment was associated with stability of remission.