Large-scale and significant expression from pseudogenes in Sodalis glossinidius – a facultative bacterial endosymbiont

The majority of bacterial genomes have high coding efficiencies, but there are some genomes of intracellular bacteria that have low gene density. The genome of the endosymbiont Sodalis glossinidius contains almost 50 % pseudogenes containing mutations that putatively silence them at the genomic level. We have applied multiple ‘omic’ strategies, combining Illumina and Pacific Biosciences Single-Molecule Real-Time DNA sequencing and annotation, stranded RNA sequencing and proteome analysis to better understand the transcriptional and translational landscape of Sodalis pseudogenes, and potential mechanisms for their control. Between 53 and 74 % of the Sodalis transcriptome remains active in cell-free culture. The mean sense transcription from coding domain sequences (CDSs) is four times greater than that from pseudogenes. Comparative genomic analysis of six Illumina-sequenced Sodalis isolates from different host Glossina species shows pseudogenes make up ~40 % of the 2729 genes in the core genome, suggesting that they are stable and/or that Sodalis is a recent introduction across the genus Glossina as a facultative symbiont. These data shed further light on the importance of transcriptional and translational control in deciphering host–microbe interactions. The combination of genomics, transcriptomics and proteomics gives a multidimensional perspective for studying prokaryotic genomes with a view to elucidating evolutionary adaptation to novel environmental niches

Neuroimaging in Parkinson's disease dementia: Connecting the dots

Dementia is a common and devastating symptom of Parkinson’s disease but the anatomical substrate remains unclear. Some evidence points towards hippocampal involvement but neuroimaging abnormalities have been reported throughout the brain and are largely inconsistent across studies. Here, we test whether these disparate neuroimaging findings for Parkinson’s disease dementia localize to a common brain network. We used a literature search to identify studies reporting neuroimaging correlates of Parkinson’s dementia (11 studies, 385 patients). We restricted our search to studies of brain atrophy and hypometabolism that compared Parkinson’s patients with dementia to those without cognitive involvement. We used a standard coordinate-based activation likelihood estimation meta-analysis to assess for consistency in the neuroimaging findings. We then used a new approach, coordinate-based network mapping, to test whether neuroimaging findings localized to a common brain network. This approach uses resting-state functional connectivity from a large cohort of normative subjects (n = 1000) to identify the network of regions connected to a reported neuroimaging coordinate. Activation likelihood estimation meta-analysis failed to identify any brain regions consistently associated with Parkinson’s dementia, showing major heterogeneity across studies. In contrast, coordinate-based network mapping found that these heterogeneous neuroimaging findings localized to a specific brain network centred on the hippocampus. Next, we tested whether this network showed symptom specificity and stage specificity by performing two further analyses. We tested symptom specificity by examining studies of Parkinson’s hallucinations (9 studies, 402 patients) that are frequently co-morbid with Parkinson’s dementia. We tested for stage specificity by using studies of mild cognitive impairment in Parkinson’s disease (15 studies, 844 patients). Coordinate-based network mapping revealed that correlates of visual hallucinations fell within a network centred on bilateral lateral geniculate nucleus and correlates of mild cognitive impairment in Parkinson’s disease fell within a network centred on posterior default mode network. In both cases, the identified networks were distinct from the hippocampal network of Parkinson’s dementia. Our results link heterogeneous neuroimaging findings in Parkinson’s dementia to a common network centred on the hippocampus. This finding was symptom and stage-specific, with implications for understanding Parkinson’s dementia and heterogeneity of neuroimaging findings in general

Grounded reality meets machine learning: A deep-narrative analysis framework for energy policy research

Text-based data sources like narratives and stories have become increasingly popular as critical insight generator in energy research and social science. However, their implications in policy application usually remain superficial and fail to fully explo

Characterization of Pro-Inflammatory Flagellin Proteins Produced by Lactobacillus ruminis and Related Motile Lactobacilli

peer-reviewedLactobacillus ruminis is one of at least twelve motile but poorly characterized species found in the genus Lactobacillus. Of these, only L. ruminis has been isolated from mammals, and this species may be considered as an autochthonous member of the gastrointestinal microbiota of humans, pigs and cows. Nine L. ruminis strains were investigated here to elucidate the biochemistry and genetics of Lactobacillus motility. Six strains isolated from humans were non-motile while three bovine isolates were motile. A complete set of flagellum biogenesis genes was annotated in the sequenced genomes of two strains, ATCC25644 (human isolate) and ATCC27782 (bovine isolate), but only the latter strain produced flagella. Comparison of the L. ruminis and L. mali DSM20444T motility loci showed that their genetic content and gene-order were broadly similar, although the L. mali motility locus was interrupted by an 11.8 Kb region encoding rhamnose utilization genes that is absent from the L. ruminis motility locus. Phylogenetic analysis of 39 motile bacteria indicated that Lactobacillus motility genes were most closely related to those of motile carnobacteria and enterococci. Transcriptome analysis revealed that motility genes were transcribed at a significantly higher level in motile L. ruminis ATCC27782 than in non-motile ATCC25644. Flagellin proteins were isolated from L. ruminis ATCC27782 and from three other Lactobacillus species, while recombinant flagellin of aflagellate L. ruminis ATCC25644 was expressed and purified from E. coli. These native and recombinant Lactobacillus flagellins, and also flagellate L. ruminis cells, triggered interleukin-8 production in cultured human intestinal epithelial cells in a manner suppressed by short interfering RNA directed against Toll-Like Receptor 5. This study provides genetic, transcriptomic, phylogenetic and immunological insights into the trait of flagellum-mediated motility in the lactobacilli.This work was supported by a Principal Investigator Award (07/IN.1/B1780) from Science Foundation Ireland to PWOT. BAN was the recipient of an Embark studentship from the Irish Research Council for Science Engineering and Technology. TD and KN were supported by the Alimentary Pharmabiotic Centre, funded by Science Foundation Ireland

Elucidating the Stability and Reactivity of Surface Intermediates on Single-Atom Alloy Catalysts

Doping isolated single atoms of a platinum-group metal into the surface of a noble-metal host is sufficient to dramatically improve the activity of the unreactive host yet also facilitates the retention of the host’s high reaction selectivity in numerous catalytic reactions. The atomically dispersed highly active sites in these single-atom alloy (SAA) materials are capable of performing facile bond activations allowing for the uptake of species onto the surface and the subsequent spillover of adspecies onto the noble host material, where selective catalysis can be performed. For example, SAAs have been shown to activate C–H bonds at low temperatures without coke formation, as well as selectively hydrogenate unsaturated hydrocarbons with excellent activity. However, to date, only a small subset of SAAs has been synthesized experimentally and it is unclear which metallic combinations may best catalyze which chemical reactions. To shed light on this issue, we have performed a widespread screening study using density functional theory to elucidate the fundamental adsorptive and catalytic properties of 12 SAAs (Ni-, Pd-, Pt-, and Rh-doped Cu(111), Ag(111), and Au(111)). We considered the interaction of these SAAs with a variety of adsorbates often found in catalysis and computed reaction mechanisms for the activation of several catalytically relevant species (H₂, CH₄, NH₃, CH₃OH, and CO₂) by SAAs. Finally, we discuss the applicability of thermochemical linear scaling and the Brønsted–Evans–Polanyi relationship to SAA systems, demonstrating that SAAs combine weak binding with low activation energies to give enhanced catalytic behavior over their monometallic counterparts. This work will ultimately facilitate the discovery and development of SAAs, serving as a guide to experimentalists and theoreticians alike

Nudges and other moral technologies in the context of power: Assigning and accepting responsibility

Strawson argues that we should understand moral responsibility in terms of our practices of holding responsible and taking responsibility. The former covers what is commonly referred to as backward-looking responsibility , while the latter covers what is commonly referred to as forward-looking responsibility . We consider new technologies and interventions that facilitate assignment of responsibility. Assigning responsibility is best understood as the second- or third-personal analogue of taking responsibility. It establishes forward-looking responsibility. But unlike taking responsibility, it establishes forward-looking responsibility in someone else. When such assignments are accepted, they function in such a way that those to whom responsibility has been assigned face the same obligations and are susceptible to the same reactive attitudes as someone who takes responsibility. One family of interventions interests us in particular: nudges. We contend that many instances of nudging tacitly assign responsibility to nudgees for actions, values, and relationships that they might not otherwise have taken responsibility for. To the extent that nudgees tacitly accept such assignments, they become responsible for upholding norms that would otherwise have fallen under the purview of other actors. While this may be empowering in some cases, it can also function in such a way that it burdens people with more responsibility that they can (reasonably be expected to) manage

Tests of amounts and times of application of nitrogen and of sequential sprays of aphicide and fungicides on winter wheat, following either beans or wheat, and the effects of take-all (Gaeumannomyces graminis var. tritici ), on two varieties at Saxmundham, Suffolk 1980-3

RESP-9258 and RESP-924

GPS-Geodetic Deformation Monitoring of the South-west Seismic Zone of Western Australia: Review, Description of Methodology and Results from Epoch-one

The south-west seismic zone (SWSZ) is a northwest-southeast trending belt of intraplate earthquake activity that occurs in the south-western corner of Western Australia, and is one of the most seismically active areas in Australia. Since the SWSZ lies as close as ~150 km from the ~1.4 million population of the Perth region, it poses a distinct seismic hazard. Earthquake activity recorded by Geoscience Australia over the past three decades suggests that the SWSZ could be deforming by 0.5-5 mmy-1. However, little is currently known about the magnitude and orientation of this deformation, and whether there is any associated surface expression. Previous geodetic studies of the SWSZ that used both terrestrial and Global Positioning System (GPS) techniques are inconclusive, due mainly to the imprecision of the technologies used in relation to the likely small amount of any surface deformation. Therefore, a new 48-point GPS-geodetic monitoring network has been established across the SWSZ to attempt to detect surface deformation, for which epoch-one episodic GPS-geodetic measurements were made in May 2002. This paper briefly reviews previous attempts to geodetically measure surface deformation across the SWSZ, summarises the scientific rationale for the new project, describes the network design and observations used, results of the May 2002 campaign (epoch-one) and discusses future work, including issues pertaining to the likely amount of surface deformation that can be detected

Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds

Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n =15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occured. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases. The immunohistochemical detection of actin-positive cells, therefore, demonstrates whether an unknown skin wound is aged approximately 5 days or more. Even though a time-dependent decrease of myofibroblasts in human granulation tissue after 31 days in human wounds seems probable, the extended presence (up to about 2 months) of these cells allows no further exact age determination of older wounds

A pantothenate suxotroph of BCG rxpressing Gag confers enhanced HIV-specific immunogenicity compared to wildtype and perfingolysin expressing strains

In tuberculosis vaccine studies, perfingolysin expressing strains (pfo) of recombinant Mycobacterium bovis (rBCG) have been shown to enhance immunogenicity as compared to wildtype strains whilst pantothenate auxotrophic strains (ΔpanCD) have been shown to be safer and more immunogenic. Our group has recently shown that rBCGΔpanCD expressing HIV-1 Gag is more immunogenic than the wildtype Pasteur strain of BCG in the murine model. In this study, a wild type strain, a ΔpanCDstrain, a pfo strain and a ΔpanCD strain expressing perfringolysin (ΔpanCDpfo) of Danish BCG were used as vectors to express HIV-1 subtype C Gag. Gag specific immune responses induced by a prime with each rBCG-Gag vaccine and boost with modified vaccinia Ankara (MVA) were compared