Within-species variation in OMV cargo proteins:The Myxococcus xanthus OMV pan-proteome

Extracellular membrane vesicles are produced by all domains of life (bacteria, archaea and eukaryotes). Bacterial extracellular vesicles (outer membrane vesicles or OMVs) are produced by outer membrane blebbing, and contain proteins, nucleic acids, virulence factors, lipids and metabolites. OMV functions depend on their internal composition, therefore understanding the proteome of OMVs, and how it varies between organisms, is imperative. Here, we report a comparative proteomic profiling of OMVs from strains of Myxococcus xanthus, a predatory species of Gram-negative myxobacteria whose secretions include secondary metabolites and hydrolytic enzymes, thought to be involved in prey lysis. Ten strains were chosen for study, of which seven had genome sequences available. The remaining three strains were genome sequenced allowing definition of the core and accessory genes and genome-derived proteins found within the pan-genome and pan-proteome respectively. OMVs were isolated from each strain and proteins identified using mass spectrometry. The M. xanthus OMV pan-proteome was found to contain tens of ‘core’ and hundreds of ‘accessory’ proteins. Properties of the OMV pan-proteome were compared with those of the pan-proteome deduced from the M. xanthus pan-genome. On average, 80% of ‘core’ OMV proteins are encoded by genes of the core genome, yet the OMV proteomes of individual strains contain subsets of core genome-derived proteins which only partially overlap. In addition, the distribution of characteristics of vesicle proteins does not correlate with the genome-derived proteome characteristic distribution. We hypothesize that M. xanthus cells package a personalized subset of proteins whose availability is only partially dictated by the presence/absence of encoding genes within the genome

Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells.

Affinity and dose of T cell receptor (TCR) interaction with antigens govern the magnitude of CD4+ T cell responses, but questions remain regarding the quantitative translation of TCR engagement into downstream signals. We find that while the response of mouse CD4+ T cells to antigenic stimulation is bimodal, activated cells exhibit analog responses proportional to signal strength. Gene expression output reflects TCR signal strength, providing a signature of T cell activation. Expression changes rely on a pre-established enhancer landscape and quantitative acetylation at AP-1 binding sites. Finally, we show that graded expression of activation genes depends on ERK pathway activation, suggesting that an ERK-AP-1 axis plays an important role in translating TCR signal strength into proportional activation of enhancers and genes essential for T cell function

A Method to Address Differential Bias in Genotyping in Large-Scale Association Studies

In a previous paper we have shown that, when DNA samples for cases and controls are prepared in different laboratories prior to high-throughput genotyping, scoring inaccuracies can lead to differential misclassification and, consequently, to increased false-positive rates. Different DNA sourcing is often unavoidable in large-scale disease association studies of multiple case and control sets. Here, we describe methodological improvements to minimise such biases. These fall into two categories: improvements to the basic clustering methods for identifying genotypes from fluorescence intensities, and use of “fuzzy” calls in association tests in order to make appropriate allowance for call uncertainty. We find that the main improvement is a modification of the calling algorithm that links the clustering of cases and controls while allowing for different DNA sourcing. We also find that, in the presence of different DNA sourcing, biases associated with missing data can increase the false-positive rate. Therefore, we propose the use of “fuzzy” calls to deal with uncertain genotypes that would otherwise be labeled as missing

Verbal learning and memory in prelingually deaf children with cochlear implants

OBJECTIVE: Deaf children with cochlear implants (CIs) show poorer verbal working memory compared to normal-hearing (NH) peers, but little is known about their verbal learning and memory (VLM) processes involving multi-trial free recall. DESIGN: Children with CIs were compared to NH peers using the California Verbal Learning Test for Children (CVLT-C). STUDY SAMPLE: Participants were 21 deaf (before age 6 months) children (6-16 years old) implanted prior to age 3 years, and 21 age-IQ matched NH peers. RESULTS: Results revealed no differences between groups in number of words recalled. However, CI users showed a pattern of increasing use of serial clustering strategies across learning trials, whereas NH peers decreased their use of serial clustering strategies. In the CI sample (but not in the NH sample), verbal working memory test scores were related to resistance to the build-up of proactive interference, and sentence recognition was associated with performance on the first exposure to the word list and to the use of recency recall strategies. CONCLUSIONS: Children with CIs showed robust evidence of VLM comparable to NH peers. However, their VLM processing (especially recency and proactive interference) was related to speech perception outcomes and verbal WM in different ways from NH peers

Book Reviews

Essential Woodworker - Skills, Tools & Materials - reviewed by John EgglestonPower Tool Woodworking - reviewed by John EgglestonAir Brushing Automobiles - Tips, Techniques and Projects - reviewed by Steve SayerChair Seating - Techniques in Cane, Rush, Willow and Cords - reviewed by Steve SayerAuthentic Craftsmanship in Interior Design - reviewed  by John EgglestonA tool for Learning - Some functions of art in the primary school - reviewed  by Brian Allison";SKILLS"; - Video series for CDT - reviewed  by David JonesStarting Embroidery - reviewed  by Moira G SimpsonSantos Statures and Sculptures - reviewed  by Brian AllisonCompendium of Lettering Workbooks - reviewed  by John LancasterDrawn Thread Embroidery Starting Needlepoint Lace - reviewed  by E. WishartBinche Lace - reviewed  by E. Wishar

Coordinated river infrastructure decisions improve net social-ecological benefits

We explore the social, ecological, economic, and technical dimensions of sustainable river infrastructure development and the potential benefits of coordinating decisions such as dam removal and stream crossing improvement. Dam removal is common practice for restoring river habitat connectivity and ecosystem health. However, stream crossings such as culverts are often 15 times more abundant than dams and may pose similar ecological impacts. Using multi-objective optimization for a model system of 6100 dams and culverts in Maine, USA, we demonstrate substantial benefit-cost improvements provided by coordinating habitat connectivity decisions. Benefit-cost efficiency improves by two orders of magnitude when coordinating more decisions across wider areas, but this approach may cause inequitable resource distribution. Culvert upgrades improve roadway safety and habitat connectivity, creating cost-effective opportunities for coordinating and cost-sharing projects between conservationists and safety managers. Benefit-cost trends indicate significant overlaps in habitat and safety goals, encouraging flexible stakeholder collaborations and cost-sharing strategies

West Nile Virus Viremia in Wild Rock Pigeons

Feral rock pigeons were screened for neutralizing antibodies to West Nile virus (WNV) during late winter/spring and summer of 2002 and 2003. Additionally, virus isolation from serum was attempted from 269 birds collected during peak transmission periods. The observed viremia levels and seroprevalence indicate that this species could be involved in amplifying WNV in urban settings