276 research outputs found

    An Algorithm for Cellular Reprogramming

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    The day we understand the time evolution of subcellular elements at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology, providing data-guided frameworks that allow us to develop better predictions about and methods for control over specific biological processes and system-wide cell behavior. In this paper we describe an approach to optimizing the use of transcription factors in the context of cellular reprogramming. We construct an approximate model for the natural evolution of a synchronized population of fibroblasts, based on data obtained by sampling the expression of some 22,083 genes at several times along the cell cycle. (These data are based on a colony of cells that have been cell cycle synchronized) In order to arrive at a model of moderate complexity, we cluster gene expression based on the division of the genome into topologically associating domains (TADs) and then model the dynamics of the expression levels of the TADs. Based on this dynamical model and known bioinformatics, we develop a methodology for identifying the transcription factors that are the most likely to be effective toward a specific cellular reprogramming task. The approach used is based on a device commonly used in optimal control. From this data-guided methodology, we identify a number of validated transcription factors used in reprogramming and/or natural differentiation. Our findings highlight the immense potential of dynamical models models, mathematics, and data guided methodologies for improving methods for control over biological processes

    Rabies Virus in Raccoons, Ohio, 2004

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    In 2004, the raccoon rabies virus variant emerged in Ohio beyond an area where oral rabies vaccine had been distributed to prevent westward spread of this variant. Our genetic investigation indicates that this outbreak may have begun several years before 2004 and may have originated within the vaccination zone

    The morphology, behaviour and molecular phylogeny of Phytophthora taxon Salixsoil and its redesignation as Phytophthora lacustris sp nov.

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    Since its first isolation from Salix roots in 1972, isolates of a sexually sterile Phytophthora species have been obtained frequently from wet or riparian habitats worldwide and have also been isolated from roots of Alnus and Prunus spp. Although originally assigned to Phytophthora gonapodyides on morphological grounds, it was recognized that these isolates, informally named P.taxon Salixsoil, might represent a separate lineage within ITS Clade 6. Based on phylogenetic analyses and comparisons of morphology, growth-temperature relationships and pathogenicity, this taxon is formally described here as Phytophthora lacustris sp. nov. Isolates of P.lacustris form a clearly resolved cluster in both ITS and mitochondrial cox1 phylogenies, basal to most other Clade 6 taxa. Phytophthora lacustris shares several unusual behavioural properties with other aquatic Clade 6 species, such as sexual sterility and tolerance of high temperatures, that have been suggested as adaptations to riparian conditions. It appears to be widespread in Europe and has also been detected in Australia, New Zealand and the USA. It was shown to be weakly or moderately aggressive on inoculation to Alnus, Prunus and Salix. The extent of P.lacustris' activity as a saprotroph in plant debris in water and as an opportunistic pathogen in riparian habitats needs further investigation. Its pathogenic potential to cultivated fruit trees also deserves attention because P.lacustris has apparently been introduced into the nursery trade.German Research Foundation at the University of Konstanz, Germany [SFB 454]; OTKA [F038325, K61107, IN64168, IN71349]; MIUR (Ministry of University and Research); MIPAF (Ministry of Agriculture and Forestry); University of Catania, Italy; Scottish Governmentinfo:eu-repo/semantics/publishedVersio

    Phytophthora acerina sp nov., a new species causing bleeding cankers and dieback of Acer pseudoplatanus trees in planted forests in northern Italy

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    A severe dieback of Acer pseudoplatanus trees was noticed in planted forest stands in northern Italy in 2010. Affected trees showed collar rot and aerial bleeding cankers along the stems, leading to crown dieback and eventually death. An unknown Phytophthora species was consistently isolated from necrotic bark and xylem tissue and from rhizosphere soil. Based on its unique combination of morphological and physiological characters and phylogenetic analysis, this new taxon is here described as Phytophthora acerina sp. nov. Phylogenetic analysis of ITS, cox1 and beta-tubulin gene regions demonstrated that P. acerina is unique and forms a separate cluster within the 'P. citricola complex', closely related to P. plurivora. Phytophthora acerina is homothallic with smooth-walled oogonia, thick-walled, mostly aplerotic oospores with a high abortion rate, paragynous antheridia, and persistent, morphologically variable semipapillate sporangia. Four to 5-week-old cultures produced globose to subglobose, appressoria-like and coralloid hyphal swellings and characteristic stromata-like hyphal aggregations. Optimum and maximum temperatures for growth are 25 degrees C and 32 degrees C, respectively. Genetic uniformity of all 15 studied isolates and the apparent absence of this species in the extensive surveys of nurseries, forests and seminatural ecosystems conducted in the previous two decades across Europe indicate a recent clonal introduction to northern Italy. Under-bark inoculation tests demonstrated high aggressiveness of P. acerina to A. pseudoplatanus indicating that this pathogen might be a serious risk to maple plantations and forests in Europe.Italia Nostra Onlus - Centro della Forestazione Urbana (CFU); Scottish Governmentinfo:eu-repo/semantics/publishedVersio

    Phytophthora pachypleura sp nov., a new species causing root rot of Aucuba japonica and other ornamentals in the United Kingdom

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    Isolates of an unknown Phytophthora species from the Phytophthora citricola complex' have been found associated with mortality of Aucuba japonica in the UK. Based on morphological characteristics, growth-temperature relationships, sequences of five DNA regions and pathogenicity assays, the proposed novel species is described as Phytophthora pachypleura. Being homothallic with paragynous antheridia and semipapillate sporangia, P.pachypleura resembles other species in the P.citricola complex' but can be discriminated by its distinctively thick-walled oospores with an oospore wall index of 071. In the phylogenetic analysis based on three nuclear (ITS, -tubulin, EF-1) and two mitochondrial (cox1, nadh1) DNA regions, P.pachypleura formed a distinct clade within the P.citricola complex' with P.citricola s. str., P.citricola E and P.acerina as its closest relatives. Phytophthora pachypleura is more aggressive to A.japonica than P.plurivora and P.multivora and has the potential to affect other ornamental species.info:eu-repo/semantics/publishedVersio

    A taxonomic and phylogenetic revision of the Penicillium sclerotiorum complex

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    The morphological concept of Penicillium sclerotiorum (subgenus Aspergilloides) includes strains with monoverticillate, vesiculate conidiophores, and vivid orange to red colony colours, with colourful sclerotia sometimes produced. Multigene phylogenetic analyses with the nuclear ribosomal internal transcribed spacer (ITS) region, cytochrome c oxidase subunit 1 (cox1), β-tubulin (benA), translation elongation factor 1-α (tef1-α), and calmodulin (cmd), reveal that the P. sclerotiorum morphospecies is a complex of seven phylogenetically distinct species, three of which were recently described, namely P. guanacastense, P. mallochii, and P. viticola. Three previously unidentified species are described here as P. cainii, P. jacksonii, and P. johnkrugii. The phylogenetic species are morphologically similar, but differ in combinations of colony characters, sclerotium production, conidiophore stipe roughening and branching, and conidial shape. Ecological characters and differences in geographical distribution further characterise some of the species, but increased sampling is necessary to confirm these differences. The fungal DNA barcode, the ITS, and the animal DNA barcode, cox1, have lower species resolving ability in our phylogenetic analyses, but still allow identification of all the species. Tef1-α and cmd were superior in providing fully resolved, statistically well-supported phylogenetic trees for this species complex, whereas benA resolved all species but had some issues with paraphyly. Penicillium adametzioides and P. multicolor, considered synonyms of P. sclerotiorum by some previous authors, do not belong to the P. sclerotiorum complex

    The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

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    © 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

    A biogeographical profile of the sand cockroach Arenivaga floridensis and its bearing on origin hypotheses for Florida scrub biota

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    Florida scrub is a xeric ecosystem associated with the peninsula’s sand ridges, whose intermittent Pliocene–Pleistocene isolation is considered key to scrub endemism. One scrub origin hypothesis posits endemics were sourced by the Pliocene dispersal of arid-adapted taxa from southwestern North America; a second invokes Pleistocene migration within eastern North America. Only one study to date has explicitly tested these competing hypotheses, supporting an eastern origin for certain scrub angiosperms. For further perspective, we conducted a genetic analysis of an endemic arthropod, the Florida sand cockroach (Arenivaga floridensis), with two aims: (1) to reconstruct the peninsular colonization and residence history of A. floridensis and (2) determine whether its biogeographic profile favors either origin hypothesis. We sequenced the cox2 mitochondrial gene for 237 specimens (65 populations) as well as additional loci (cox1, nuclear H3) for a subset of Florida roaches and congeners. Using Network and Bayesian inference methods, we identified three major lineages whose genetic differentiation and phylogeographical structure correspond with late Pliocene peninsula insularization, indicating Arenivaga was present and broadly distributed in Florida at that time. Stem and crown divergence estimates (6.36 Ma; 2.78 Ma) between A. floridensis and western sister taxa span a period of extensive dispersal by western biota along an arid Gulf Coast corridor. These phylogeographical and phylogenetic results yield a biogeographic profile consistent with the western origin hypothesis. Moreover, age estimates for the roach’s peninsular residence complement those of several other endemics, favoring a Pliocene (or earlier) inception of the scrub ecosystem. We argue that eastern versus western hypotheses are not mutually exclusive; rather, a composite history of colonization involving disparate biotas better explains the diverse endemism of Florida scrub

    Relationship between wild greylag and European domestic geese based on mitochondrial DNA.

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    The origins of the European domestic goose are uncertain. The available information comes from archaeological findings and historical literature, but genetic evidence has hitherto been scarce. The domestic goose in Europe is derived from the greylag goose (Anser anser), but it is not known where the initial domestication took place and which of the two subspecies of greylag goose was ancestral. We aimed to determine the amount and geographical distribution of genetic diversity in modern populations of greylag geese as well as in different breeds of the domestic goose to make inferences about goose domestication. We studied DNA sequence variation in the mitochondrial control region of greylag geese from multiple populations across Europe and western Asia as well as specimens of domestic geese representing 18 modern breeds and individuals not belonging to any recognised breed. Our results show notable differences in genetic diversity between different greylag goose populations and the presence of six mitochondrial haplogroups which show a degree of geographical partitioning. The genetic diversity of the domestic goose is low, with 84% of sampled individuals having one of two major closely related haplotypes, suggesting that modern European domestic geese may derive from a narrow genetic base. The site of domestication remains unresolved, but domestic geese in Turkey were unusually diverse, indicating the importance of further sampling in the vicinity of the eastern Mediterranean and the Near East. There appears to be past or ongoing hybridisation between greylags and domestic geese in particular areas, consistent with field observations
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