Ancestral function and diversification of a horizontally acquired oomycete carboxylic acid transporter

This is the author accepted manuscript. The final version is available from OUP via the DOI in this recordHorizontal gene transfer (HGT) can equip organisms with novel genes, expanding the repertoire of genetic material available for evolutionary innovation and allowing recipient lineages to colonise new environments. However, few studies have characterised the functions of HGT genes experimentally or examined post-acquisition functional divergence. Here we report the use of ancestral sequence reconstruction and heterologous expression in Saccharomyces cerevisiae to examine the evolutionary history of an oomycete transporter gene family that was horizontally acquired from fungi. We demonstrate that the inferred ancestral oomycete HGT transporter proteins and their extant descendants are predominantly localised to the plasma membrane when expressed in yeast, and that they transport dicarboxylic acids which are intermediates of the tricarboxylic acid cycle. The substrate specificity profile of the most ancestral protein has largely been retained throughout the radiation of oomycetes, including in both plant and animal pathogens and in a free-living saprotroph, indicating that the ancestral HGT transporter function has been maintained by selection across a range of different lifestyles. No evidence of neofunctionalization in terms of substrate specificity was detected for different HGT transporter paralogues which have different patterns of temporal expression. However, a striking expansion of substrate range was observed for one plant pathogenic oomycete, with a HGT derived paralogue from Pythium aphanidermatum encoding a protein that enables tricarboxylic acid uptake in addition to dicarboxylic acid uptake. This demonstrates that HGT acquisitions can provide functional additions to the recipient proteome as well as the foundation material for the evolution of new protein functions.This work was supported by a Philip Leverhulme Award to T. A. R. We acknowledge related project funding from the Gordon and Betty Moore Foundation (GBMF5514). T.A.R. is supported by a Royal Society University Research Fellowshi

Equivalence of switching linear systems by bisimulation

A general notion of hybrid bisimulation is proposed for the class of switching linear systems. Connections between the notions of bisimulation-based equivalence, state-space equivalence, algebraic and input–output equivalence are investigated. An algebraic characterization of hybrid bisimulation and an algorithmic procedure converging in a finite number of steps to the maximal hybrid bisimulation are derived. Hybrid state space reduction is performed by hybrid bisimulation between the hybrid system and itself. By specializing the results obtained on bisimulation, also characterizations of simulation and abstraction are derived. Connections between observability, bisimulation-based reduction and simulation-based abstraction are studied.\ud \u

Suicidality and hostility following involuntary hospital treatment

Background Psychiatric patients showing risk to themselves or others can be involuntarily hospitalised. No data is available on whether following hospitalisation there is a reduction in psychopathological indicators of risk such as suicidality and hostility. This study aimed to assess changes in suicidality and hostility levels following involuntary admission and their patient-level predictors. Methods A pooled analysis of studies on involuntary treatment, including 11 countries and 2790 patients was carried out. Suicidality and hostility were measured by the Brief Psychiatric Rating Scale. Results 2790 patients were included; 2129 followed-up after one month and 1864 after three months. 387 (13.9%) patients showed at least moderate suicidality when involuntarily admitted, 107 (5.0%) after one month and 97 (5.2%) after three months. Moderate or higher hostility was found in 1287 (46.1%) patients after admission, 307 (14.5%) after one month, and 172 (9.2%) after three months. Twenty-three (1.2%) patients showed suicidality, and 53 (2.8%) patients hostility at all time-points. Predictors of suicidality three months after admission were: suicidality at baseline, not having a diagnosis of psychotic disorder and being unemployed. Predictors of hostility were: hostility at baseline, not having a psychotic disorder, living alone, and having been hospitalized previously. Conclusions After involuntary hospital admission, the number of patients with significant levels of suicidality and hostility decreases substantially over time, and very few patients show consistently moderate or higher levels of these symptoms. In patients with psychotic disorders these symptoms are more likely to improve. Social factors such as unemployment and isolation could hamper suicidality and hostility reduction and may be targeted in interventions to reduce risk in involuntarily admitted patients

Exogenous spatial precuing reliably modulates object processing but not object substitution masking

Object substitution masking (OSM) is used in behavioral and imaging studies to investigate processes associated with the formation of a conscious percept. Reportedly, OSM occurs only when visual attention is diffusely spread over a search display or focused away from the target location. Indeed, the presumed role of spatial attention is central to theoretical accounts of OSM and of visual processing more generally (Di Lollo, Enns, & Rensink, Journal of Experimental Psychology: General 129:481–507, 2000). We report a series of five experiments in which valid spatial precuing is shown to enhance the ability of participants to accurately report a target but, in most cases, without affecting OSM. In only one experiment (Experiment 5) was a significant effect of precuing observed on masking. This is in contrast to the reliable effect shown across all five experiments in which precuing improved overall performance. The results are convergent with recent findings from Argyropoulos, Gellatly, and Pilling (Journal of Experimental Psychology: Human Perception and Performance 39:646–661, 2013), which show that OSM is independent of the number of distractor items in a display. Our results demonstrate that OSM can operate independently of focal attention. Previous claims of the strong interrelationship between OSM and spatial attention are likely to have arisen from ceiling or floor artifacts that restricted measurable performance

Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages

There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the 'Beijing' sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive

Exclusive Leptoproduction of rho^0 Mesons from Hydrogen at Intermediate Virtual Photon Energies

Measurements of the cross section for exclusive virtual-photoproduction of rho^0 mesons from hydrogen are reported. The data were collected by the HERMES experiment using 27.5 GeV positrons incident on a hydrogen gas target in the HERA storage ring. The invariant mass W of the photon-nucleon system ranges from 4.0 to 6.0 GeV, while the negative squared four-momentum Q^2 of the virtual photon varies from 0.7 to 5.0 GeV^2. The present data together with most of the previous data at W > 4 GeV are well described by a model that infers the W-dependence of the cross section from the dependence on the Bjorken scaling variable x of the unpolarized structure function for deep-inelastic scattering. In addition, a model calculation based on Off-Forward Parton Distributions gives a fairly good account of the longitudinal component of the rho^0 production cross section for Q^2 > 2 GeV^2.Comment: 10 pages, 6 embedded figures, LaTeX for SVJour(epj) document class. Revisions: curves added to Fig. 1, several clarifications added to tex

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Unexpected mitochondrial genome diversity revealed by targeted single-cell genomics of heterotrophic flagellated protists

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: Complete mtDNA sequences assembled from this study are available at GenBank under the accession numbers MK188935 to MK188947, MN082144 and MN082145. Sequencing data are available under NCBI BioProject PRJNA379597. Reads have been deposited at NCBI Sequence Read Archive with accession number SRP102236. Partial mtDNA contigs and other important contigs mentioned in the text are available from Figshare at https://doi.org/10.6084/m9.figshare.7314728. Nuclear SAG assemblies are available from Figshare at https://doi.org/10.6084/m9.figshare.7352966. A protocol is available from protocols.io at: https://doi.org/10.17504/protocols.io.ywpfxdn.Code availability: The bioinformatic workflow is available at https://doi.org/10.5281/zenodo.192677; additional statistical analysis code is available at https://doi.org/10.6084/m9.figshare.9884309.Most eukaryotic microbial diversity is uncultivated, under-studied and lacks nuclear genome data. Mitochondrial genome sampling is more comprehensive, but many phylogenetically important groups remain unsampled. Here, using a single-cell sorting approach combining tubulin-specific labelling with photopigment exclusion, we sorted flagellated heterotrophic unicellular eukaryotes from Pacific Ocean samples. We recovered 206 single amplified genomes, predominantly from underrepresented branches on the tree of life. Seventy single amplified genomes contained unique mitochondrial contigs, including 21 complete or near-complete mitochondrial genomes from formerly under-sampled phylogenetic branches, including telonemids, katablepharids, cercozoans and marine stramenopiles, effectively doubling the number of available samples of heterotrophic flagellate mitochondrial genomes. Collectively, these data identify a dynamic history of mitochondrial genome evolution including intron gain and loss, extensive patterns of genetic code variation and complex patterns of gene loss. Surprisingly, we found that stramenopile mitochondrial content is highly plastic, resembling patterns of variation previously observed only in plants.Gordon and Betty Moore FoundationLeverhulme TrustDavid and Lucile Packard FoundationRoyal SocietyEuropean Molecular Biology OrganizationCONICYT FONDECYTGenome Canad

Emergent RNA–RNA interactions can promote stability in a facultative phototrophic endosymbiosis

This is the final version. Available on open access from the National Academy of Sciences via the DOI in this recordData Availability: The sequence data, code, and datasets have been deposited in NCBI Sequence Read Archive, GitHub, Figshare, and Zenodo. The raw reads generated during sRNA sequencing are available on the NCBI Sequence Read Archive (accession numbers SAMN14932981 and SAMN14932982). All other datasets are available on Figshare (https://doi.org/10.6084/m9.figshare.c.4978160.v3) under the relevant headings (77). Custom scripts for sRNA read processing (https://github.com/guyleonard/paramecium, https://doi.org/10.5281/zenodo.4638888) and eDicer comparative analysis (https://github.com/fmaguire/eDicer, https://doi.org/10.5281/zenodo.4659378) are available on GitHub and archived within the Zenodo repository.Eukaryote–eukaryote endosymbiosis was responsible for the spread of chloroplast (plastid) organelles. Stability is required for the metabolic and genetic integration that drives the establishment of new organelles, yet the mechanisms that act to stabilize emergent endosymbioses—between two fundamentally selfish biological organisms—are unclear. Theory suggests that enforcement mechanisms, which punish misbehavior, may act to stabilize such interactions by resolving conflict. However, how such mechanisms can emerge in a facultative endosymbiosis has yet to be explored. Here, we propose that endosymbiont–host RNA–RNA interactions, arising from digestion of the endosymbiont population, can result in a cost to host growth for breakdown of the endosymbiosis. Using the model facultative endosymbiosis between Paramecium bursaria and Chlorella spp., we demonstrate that this mechanism is dependent on the host RNA-interference (RNAi) system. We reveal through small RNA (sRNA) sequencing that endosymbiont-derived messenger RNA (mRNA) released upon endosymbiont digestion can be processed by the host RNAi system into 23-nt sRNA. We predict multiple regions of shared sequence identity between endosymbiont and host mRNA, and demonstrate through delivery of synthetic endosymbiont sRNA that exposure to these regions can knock down expression of complementary host genes, resulting in a cost to host growth. This process of host gene knockdown in response to endosymbiont-derived RNA processing by host RNAi factors, which we term “RNAi collisions,” represents a mechanism that can promote stability in a facultative eukaryote–eukaryote endosymbiosis. Specifically, by imposing a cost for breakdown of the endosymbiosis, endosymbiont–host RNA–RNA interactions may drive maintenance of the symbiosis across fluctuating ecological conditions.European Molecular Biology OrganizationRoyal SocietyEuropean Research Council (ERC)Wellcome TrustLister InstituteDonald Hill Family Fellowshi