Neutral genomic microevolution of a recently emerged pathogen, salmonella enterica serovar agona

Salmonella enterica serovar Agona has caused multiple food-borne outbreaks of gastroenteritis since it was first isolated in 1952. We analyzed the genomes of 73 isolates from global sources, comparing five distinct outbreaks with sporadic infections as well as food contamination and the environment. Agona consists of three lineages with minimal mutational diversity: only 846 single nucleotide polymorphisms (SNPs) have accumulated in the non-repetitive, core genome since Agona evolved in 1932 and subsequently underwent a major population expansion in the 1960s. Homologous recombination with other serovars of S. enterica imported 42 recombinational tracts (360 kb) in 5/143 nodes within the genealogy, which resulted in 3,164 additional SNPs. In contrast to this paucity of genetic diversity, Agona is highly diverse according to pulsed-field gel electrophoresis (PFGE), which is used to assign isolates to outbreaks. PFGE diversity reflects a highly dynamic accessory genome associated with the gain or loss (indels) of 51 bacteriophages, 10 plasmids, and 6 integrative conjugational elements (ICE/IMEs), but did not correlate uniquely with outbreaks. Unlike the core genome, indels occurred repeatedly in independent nodes (homoplasies), resulting in inaccurate PFGE genealogies. The accessory genome contained only few cargo genes relevant to infection, other than antibiotic resistance. Thus, most of the genetic diversity within this recently emerged pathogen reflects changes in the accessory genome, or is due to recombination, but these changes seemed to reflect neutral processes rather than Darwinian selection. Each outbreak was caused by an independent clade, without universal, outbreak-associated genomic features, and none of the variable genes in the pan-genome seemed to be associated with an ability to cause outbreaks

Hepatitis C quasispecies adaptation in the setting of a variable fidelity polymerase

Hepatitis C (HCV) is a virus characterized by an RNA-dependent RNA polymerase that lacks a proofreading mechanism and, as a result, generates a quasispecies. There is emerging evidence that this RNA-dependent RNA polymerase may in fact have variable fidelity. Here, we review the relevant concepts, including fitness landscapes, clonal interference, robustness, selection, adaptation, mutation rates, and their optimization, and provide a unique interpretation of a number of relevant theoretical models, evolving the theory of replicative homeostasis in light of their findings. We suggest that a variable fidelity polymerase can find its own optimal mutation rate, which is governed by the sequence itself and certain population dynamics. We propose that this concept can explain features of viral kinetics and clearance, both spontaneously and following treatment of chronic HCV. We point to evidence that supports this theory and explain how it refines replicative homeostasis and conclude by discussing particular areas of potential research that might augment our understanding of viral host interactions at an individual cellular level

Crustal evolution between 2.0 and 3.5 Ga in the southern Gaviao block (Umburanas-Brumado-Aracatu region), Sao Francisco Craton, Brazil: A 3.5-3.8 Ga photo-crust in the Gaviao block?

The main evolution of the Gavião block in the Umburanas-Brumado-Aracatu region, in the state of Bahia, is defined by several sets of tonalitic-trondhjemitic and granodioritic gneisses emplaced during the Paleoarchean. The juvenile Bernada gneisses are e

e-Skills: The International dimension and the Impact of Globalisation - Final Report 2014

In today’s increasingly knowledge-based economies, new information and communication technologies are a key engine for growth fuelled by the innovative ideas of highly - skilled workers. However, obtaining adequate quantities of employees with the necessary e-skills is a challenge. This is a growing international problem with many countries having an insufficient numbers of workers with the right e-Skills. For example: Australia: “Even though there’s 10,000 jobs a year created in IT, there are only 4500 students studying IT at university, and not all of them graduate” (Talevski and Osman, 2013). Brazil: “Brazil’s ICT sector requires about 78,000 [new] people by 2014. But, according to Brasscom, there are only 33,000 youths studying ICT related courses in the country” (Ammachchi, 2012). Canada: “It is widely acknowledged that it is becoming inc reasingly difficult to recruit for a variety of critical ICT occupations –from entry level to seasoned” (Ticoll and Nordicity, 2012). Europe: It is estimated that there will be an e-skills gap within Europe of up to 900,000 (main forecast scenario) ICT pr actitioners by 2020” (Empirica, 2014). Japan: It is reported that 80% of IT and user companies report an e-skills shortage (IPA, IT HR White Paper, 2013) United States: “Unlike the fiscal cliff where we are still peering over the edge, we careened over the “IT Skills Cliff” some years ago as our economy digitalized, mobilized and further “technologized”, and our IT skilled labour supply failed to keep up” (Miano, 2013)

Su(dx) E3 ubiquitin ligase–dependent and –independent functions of Polychaetoid, the Drosophila ZO-1 homologue

Polychaetoid coordinates receptor trafficking and signaling with adherens junction organization

Sedentary time in older men and women: an international consensus statement and research priorities

Sedentary time is a modifiable determinant of poor health, and in older adults, reducing sedentary time may be an important first step in adopting and maintaining a more active lifestyle. The primary purpose of this consensus statement is to provide an integrated perspective on current knowledge and expert opinion pertaining to sedentary behaviour in older adults on the topics of measurement, associations with health outcomes, and interventions. A secondary yet equally important purpose is to suggest priorities for future research and knowledge translation based on gaps identified. A five-step Delphi consensus process was used. Experts in the area of sedentary behaviour and older adults (n=15) participated in three surveys, an in-person consensus meeting, and a validation process. The surveys specifically probed measurement, health outcomes, interventions, and research priorities. The meeting was informed by a literature review and conference symposium, and it was used to create statements on each of the areas addressed in this document. Knowledge users (n=3) also participated in the consensus meeting. Statements were then sent to the experts for validation. It was agreed that self-report tools need to be developed for understanding the context in which sedentary time is accumulated. For health outcomes, it was agreed that the focus of sedentary time research in older adults needs to include geriatric-relevant health outcomes, that there is insufficient evidence to quantify the dose-response relationship, that there is a lack of evidence on sedentary time from older adults in assisted facilities, and that evidence on the association between sedentary time and sleep is lacking. For interventions, research is needed to assess the impact that reducing sedentary time, or breaking up prolonged bouts of sedentary time has on geriatric-relevant health outcomes. Research priorities listed for each of these areas should be considered by researchers and funding agencies

Genomic diversity of Salmonella enterica -The UoWUCC 10K genomes project

Background: Most publicly available genomes of Salmonella enterica are from human disease in the US and the UK, or from domesticated animals in the US. Methods: Here we describe a historical collection of 10,000 strains isolated between 1891-2010 in 73 different countries. They encompass a broad range of sources, ranging from rivers through reptiles to the diversity of all S. enterica isolated on the island of Ireland between 2000 and 2005. Genomic DNA was isolated, and sequenced by Illumina short read sequencing. Results: The short reads are publicly available in the Short Reads Archive. They were also uploaded to EnteroBase , which assembled and annotated draft genomes. 9769 draft genomes which passed quality control were genotyped with multiple levels of multilocus sequence typing, and used to predict serovars. Genomes were assigned to hierarchical clusters on the basis of numbers of pair-wise allelic differences in core genes, which were mapped to genetic Lineages within phylogenetic trees. Conclusions: The University of Warwick/University College Cork (UoWUCC) project greatly extends the geographic sources, dates and core genomic diversity of publicly available S. enterica genomes. We illustrate these features by an overview of core genomic Lineages within 33,000 publicly available Salmonella genomes whose strains were isolated before 2011. We also present detailed examinations of HC400, HC900 and HC2000 hierarchical clusters within exemplar Lineages, including serovars Typhimurium, Enteritidis and Mbandaka. These analyses confirm the polyphyletic nature of multiple serovars while showing that discrete clusters with geographical specificity can be reliably recognized by hierarchical clustering approaches. The results also demonstrate that the genomes sequenced here provide an important counterbalance to the sampling bias which is so dominant in current genomic sequencing

The DESI Sky Continuum Monitor System

The Dark Energy Spectroscopic Instrument (DESI) is an ongoing spectroscopic survey to measure the dark energy equation of state to unprecedented precision. We describe the DESI Sky Continuum Monitor System, which tracks the night sky brightness as part of a system that dynamically adjusts the spectroscopic exposure time to produce more uniform data quality and to maximize observing efficiency. The DESI dynamic exposure time calculator (ETC) will combine sky brightness measurements from the Sky Monitor with data from the guider system to calculate the exposure time to achieve uniform signal-to-noise ratio (SNR) in the spectra under various observing conditions. The DESI design includes 20 sky fibers, and these are split between two identical Sky Monitor units to provide redundancy. Each Sky Monitor unit uses an SBIG STXL-6303e CCD camera and supports an eight-position filter wheel. Both units have been completed and delivered to the Mayall Telescope at the Kitt Peak National Observatory. Commissioning results show that the Sky Monitor delivers the required performance necessary for the ETC.Comment: 9 pages, 7 figures, 1 tabl

ZO-1 Stabilizes the Tight Junction Solute Barrier through Coupling to the Perijunctional Cytoskeleton

ZO-1 binds numerous transmembrane and cytoplasmic proteins and is required for assembly of both adherens and tight junctions, but its role in defining barrier properties of an established tight junction is unknown. We depleted ZO-1 in MDCK cells using siRNA methods and observed specific defects in the barrier for large solutes, even though flux through the small claudin pores was unaffected. This permeability increase was accompanied by morphological alterations and reorganization of apical actin and myosin. The permeability defect, and to a lesser extent morphological changes, could be rescued by reexpression of either full-length ZO-1 or an N-terminal construct containing the PDZ, SH3, and GUK domains. ZO-2 knockdown did not replicate either the permeability or morphological phenotypes seen in the ZO-1 knockdown, suggesting that ZO-1 and -2 are not functionally redundant for these functions. Wild-type and knockdown MDCK cells had differing physiological and morphological responses to pharmacologic interventions targeting myosin activity. Use of the ROCK inhibitor Y27632 or myosin inhibitor blebbistatin increased TER in wild-type cells, whereas ZO-1 knockdown monolayers were either unaffected or changed in the opposite direction; paracellular flux and myosin localization were also differentially affected. These studies are the first direct evidence that ZO-1 limits solute permeability in established tight junctions, perhaps by forming a stabilizing link between the barrier and perijunctional actomyosin