1,165 research outputs found
Shut Tight Dose Winkin\u27 Blinkin\u27 Eyes / words by Thomas Curtis Clark
Key of Eb. Cover: A southern lullaby, a drawing of trees; Publisher: The Thompson Music Co. (Chicago)https://egrove.olemiss.edu/sharris_b/1054/thumbnail.jp
The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
Our understanding of the activity of cationic antimicrobial peptides (AMPs) has focused on well-characterized natural sequences, or limited sets of synthetic peptides designed de novo. We have undertaken a comprehensive investigation of the underlying primary structural features that give rise to the development of activity in AMPs. We consider a complete set of all possible peptides, up to 7 residues long, composed of positively charged arginine (R) and / or hydrophobic tryptophan (W), two features most commonly associated with activity. We found the shortest active peptides were 4 or 5 residues in length, and the overall landscapes of activity against gram-positive and gram-negative bacteria and a yeast were positively correlated. For all three organisms we found a single activity peak corresponding to sequences with around 40% R; the presence of adjacent W duplets and triplets also conferred greater activity. The mechanistic basis of these activities comprises a combination of lipid binding, particularly to negatively charged membranes, and additionally peptide aggregation, a mode of action previously uninvestigated for such peptides. The maximum specific antimicrobial activity appeared to occur in peptides of around 10 residues, suggesting ‘diminishing returns’ for developing larger peptides, when activity is considered per residue of peptide
The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences
From Springer Nature via Jisc Publications RouterHistory: received 2020-08-09, accepted 2021-03-29, registration 2021-04-24, pub-electronic 2021-05-21, online 2021-05-21, collection 2021-12Publication status: PublishedFunder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268; Grant(s): BB/M011208/1Abstract: Our understanding of the activity of cationic antimicrobial peptides (AMPs) has focused on well-characterized natural sequences, or limited sets of synthetic peptides designed de novo. We have undertaken a comprehensive investigation of the underlying primary structural features that give rise to the development of activity in AMPs. We consider a complete set of all possible peptides, up to 7 residues long, composed of positively charged arginine (R) and / or hydrophobic tryptophan (W), two features most commonly associated with activity. We found the shortest active peptides were 4 or 5 residues in length, and the overall landscapes of activity against gram-positive and gram-negative bacteria and a yeast were positively correlated. For all three organisms we found a single activity peak corresponding to sequences with around 40% R; the presence of adjacent W duplets and triplets also conferred greater activity. The mechanistic basis of these activities comprises a combination of lipid binding, particularly to negatively charged membranes, and additionally peptide aggregation, a mode of action previously uninvestigated for such peptides. The maximum specific antimicrobial activity appeared to occur in peptides of around 10 residues, suggesting ‘diminishing returns’ for developing larger peptides, when activity is considered per residue of peptide
Automated construction and testing of multi-locus gene–gene associations
Summary: It has been argued that the missing heritability in common diseases may be in part due to rare variants and gene–gene effects. Haplotype analyses provide more power for rare variants and joint analyses across genes can address multi-gene effects. Currently, methods are lacking to perform joint multi-locus association analyses across more than one gene/region. Here, we present a haplotype-mining gene–gene analysis method, which considers multi-locus data for two genes/regions simultaneously. This approach extends our single region haplotype-mining algorithm, hapConstructor, to two genes/regions. It allows construction of multi-locus SNP sets at both genes and tests joint gene–gene effects and interactions between single variants or haplotype combinations. A Monte Carlo framework is used to provide statistical significance assessment of the joint and interaction statistics, thus the method can also be used with related individuals. This tool provides a flexible data-mining approach to identifying gene–gene effects that otherwise is currently unavailable
VarGoats project : a dataset of 1159 whole-genome sequences to dissect Capra hircus global diversity
Since their domestication 10,500 years ago, goat populations with distinctive genetic backgrounds have adapted to a broad variety of environments and breeding conditions. The VarGoats project is an international 1000-genome resequencing program designed to understand the consequences of domestication and breeding on the genetic diversity of domestic goats and to elucidate how speciation and hybridization have modeled the genomes of a set of species representative of the genus Capra. A dataset comprising 652 sequenced goats and 507 public goat sequences, including 35 animals representing eight wild species, has been collected worldwide. We identified 74,274,427 single nucleotide polymorphisms (SNPs) and 13,607,850 insertion-deletions (InDels) by aligning these sequences to the latest version of the goat reference genome (ARS1). A Neighbor-joining tree based on Reynolds genetic distances showed that goats from Africa, Asia and Europe tend to group into independent clusters. Because goat breeds from Oceania and Caribbean (Creole) all derive from imported animals, they are distributed along the tree according to their ancestral geographic origin. We report on an unprecedented international effort to characterize the genome-wide diversity of domestic goats. This large range of sequenced individuals represents a unique opportunity to ascertain how the demographic and selection processes associated with post-domestication history have shaped the diversity of this species. Data generated for the project will also be extremely useful to identify deleterious mutations and polymorphisms with causal effects on complex traits, and thus will contribute to new knowledge that could be used in genomic prediction and genome-wide association studies
Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS)
The capabilities of current computer simulations provide a unique opportunity to model small-angle scattering (SAS) data at the atomistic level, and to include other structural constraints ranging from molecular and atomistic energetics to crystallography, electron microscopy and NMR. This extends the capabilities of solution scattering and provides deeper insights into the physics and chemistry of the systems studied. Realizing this potential, however, requires integrating the experimental data with a new generation of modelling software. To achieve this, the CCP-SAS collaboration (http://www.ccpsas.org/) is developing open-source, high-throughput and user-friendly software for the atomistic and coarse-grained molecular modelling of scattering data. Robust state-of-the-art molecular simulation engines and molecular dynamics and Monte Carlo force fields provide constraints to the solution structure inferred from the small-angle scattering data, which incorporates the known physical chemistry of the system. The implementation of this software suite involves a tiered approach in which GenApp provides the deployment infrastructure for running applications on both standard and high-performance computing hardware, and SASSIE provides a workflow framework into which modules can be plugged to prepare structures, carry out simulations, calculate theoretical scattering data and compare results with experimental data. GenApp produces the accessible web-based front end termed SASSIE-web, and GenApp and SASSIE also make community SAS codes available. Applications are illustrated by case studies: (i) inter-domain flexibility in two- to six-domain proteins as exemplified by HIV-1 Gag, MASP and ubiquitin; (ii) the hinge conformation in human IgG2 and IgA1 antibodies; (iii) the complex formed between a hexameric protein Hfq and mRNA; and (iv) synthetic 'bottlebrush' polymers
Haplotype association analyses in resources of mixed structure using Monte Carlo testing
<p>Abstract</p> <p>Background</p> <p>Genomewide association studies have resulted in a great many genomic regions that are likely to harbor disease genes. Thorough interrogation of these specific regions is the logical next step, including regional haplotype studies to identify risk haplotypes upon which the underlying critical variants lie. Pedigrees ascertained for disease can be powerful for genetic analysis due to the cases being enriched for genetic disease. Here we present a Monte Carlo based method to perform haplotype association analysis. Our method, hapMC, allows for the analysis of full-length and sub-haplotypes, including imputation of missing data, in resources of nuclear families, general pedigrees, case-control data or mixtures thereof. Both traditional association statistics and transmission/disequilibrium statistics can be performed. The method includes a phasing algorithm that can be used in large pedigrees and optional use of pseudocontrols.</p> <p>Results</p> <p>Our new phasing algorithm substantially outperformed the standard expectation-maximization algorithm that is ignorant of pedigree structure, and hence is preferable for resources that include pedigree structure. Through simulation we show that our Monte Carlo procedure maintains the correct type 1 error rates for all resource types. Power comparisons suggest that transmission-disequilibrium statistics are superior for performing association in resources of only nuclear families. For mixed structure resources, however, the newly implemented pseudocontrol approach appears to be the best choice. Results also indicated the value of large high-risk pedigrees for association analysis, which, in the simulations considered, were comparable in power to case-control resources of the same sample size.</p> <p>Conclusions</p> <p>We propose hapMC as a valuable new tool to perform haplotype association analyses, particularly for resources of mixed structure. The availability of meta-association and haplotype-mining modules in our suite of Monte Carlo haplotype procedures adds further value to the approach.</p
THE COMMUNITY LEVERAGED UNIFIED ENSEMBLE (CLUE) IN THE 2016 NOAA/HAZARDOUS WEATHER TESTBED SPRING FORECASTING EXPERIMENT
One primary goal of annual Spring Forecasting Experiments (SFEs), which are coorganized by NOAA’s National Severe Storms Laboratory and Storm Prediction Center and conducted in the National Oceanic and Atmospheric Administration’s (NOAA) Hazardous Weather Testbed, is documenting performance characteristics of experimental, convection-allowing modeling systems (CAMs). Since 2007, the number of CAMs (including CAM ensembles) examined in the SFEs has increased dramatically, peaking at six different CAM ensembles in 2015. Meanwhile, major advances have been made in creating, importing, processing, verifying, and developing tools for analyzing and visualizing these large and complex datasets. However, progress toward identifying optimal CAM ensemble configurations has been inhibited because the different CAM systems have been independently designed, making it difficult to attribute differences in performance characteristics. Thus, for the 2016 SFE, a much more coordinated effort among many collaborators was made by agreeing on a set of model specifications (e.g., model version, grid spacing, domain size, and physics) so that the simulations contributed by each collaborator could be combined to form one large, carefully designed ensemble known as the Community Leveraged Unified Ensemble (CLUE). The 2016 CLUE was composed of 65 members contributed by five research institutions and represents an unprecedented effort to enable an evidence-driven decision process to help guide NOAA’s operational modeling efforts. Eight unique experiments were designed within the CLUE framework to examine issues directly relevant to the design of NOAA’s future operational CAM-based ensembles. This article will highlight the CLUE design and present results from one of the experiments examining the impact of single versus multicore CAM ensemble configurations
THE COMMUNITY LEVERAGED UNIFIED ENSEMBLE (CLUE) IN THE 2016 NOAA/HAZARDOUS WEATHER TESTBED SPRING FORECASTING EXPERIMENT
One primary goal of annual Spring Forecasting Experiments (SFEs), which are coorganized by NOAA’s National Severe Storms Laboratory and Storm Prediction Center and conducted in the National Oceanic and Atmospheric Administration’s (NOAA) Hazardous Weather Testbed, is documenting performance characteristics of experimental, convection-allowing modeling systems (CAMs). Since 2007, the number of CAMs (including CAM ensembles) examined in the SFEs has increased dramatically, peaking at six different CAM ensembles in 2015. Meanwhile, major advances have been made in creating, importing, processing, verifying, and developing tools for analyzing and visualizing these large and complex datasets. However, progress toward identifying optimal CAM ensemble configurations has been inhibited because the different CAM systems have been independently designed, making it difficult to attribute differences in performance characteristics. Thus, for the 2016 SFE, a much more coordinated effort among many collaborators was made by agreeing on a set of model specifications (e.g., model version, grid spacing, domain size, and physics) so that the simulations contributed by each collaborator could be combined to form one large, carefully designed ensemble known as the Community Leveraged Unified Ensemble (CLUE). The 2016 CLUE was composed of 65 members contributed by five research institutions and represents an unprecedented effort to enable an evidence-driven decision process to help guide NOAA’s operational modeling efforts. Eight unique experiments were designed within the CLUE framework to examine issues directly relevant to the design of NOAA’s future operational CAM-based ensembles. This article will highlight the CLUE design and present results from one of the experiments examining the impact of single versus multicore CAM ensemble configurations
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