416 research outputs found

    Geometry of the Pleistocene Rock Bodies and Erosional Surfaces Around Ames, Iowa

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    Five rock bodies and four major erosional surfaces are recognized in the subsurface; these are a lower till Kansan(?), a middle till Tazewell(?), a middle silt, an upper till (Cary), and a complexly interconnecting sand and gravel body. Erosion surfaces occur at the top of each rock body. The lower till is confined to the Squaw Buried Valley where it reaches a maximum thickness of 100 feet. The middle till averages 40 feet in thickness but ranges from 100 feet in buried valleys to absent over bedrock topographic highs. The middle silt is largely confined to the Squaw Buried Valley where it reaches thicknesses of 60 feet. The Cary till mantles the area, reaching thicknesses of over 100 feet in bedrock valleys and thinning to less than 25 feet over bedrock uplands. The distribution of the rock bodies suggests that the Squaw Buried Valley ceased to be the major drainage after Kansan (?) deposition and that the amount of pre-Tazewell (?) erosion was sufficient to remove all Kansan (?) drift from the uplands. The discontinuous distribution of the middle silt and Tazewell (?) till on the bedrock uplands indicates that erosion by the Cary glacier removed much of these rock bodies. The shape of the modern landscape mimics the shape of the buried bedrock valleys, though the relief in the area decreased from over 100 feet in pre-Kansan times to around 50 feet in pre-Cary times. The comparison of depositional landforms on the Cary surface to the till thicknesses suggests that washboard moraines. transverse features and circular features become dominant with progressively greater till thicknesses

    Functional and Epigenetic Studies Reveal Multistep Differentiation and Plasticity of In Vitro-Generated and In Vivo-Derived Follicular T Helper Cells

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    Follicular T helper (Tfh) cells provide critical help to B cells for germinal center (GC) formation. Mutations affecting SLAM-associated protein (SAP) prevent GC formation because of defective T cell-B cell interactions, yet effects on Tfh cell differentiation remain unclear. We describe the in vitro differentiation of functionally competent ā€œTfh-likeā€ cells that expressed interleukin-21, Tfh cell markers, and Bcl6 and rescued GC formation in SAP-deficient hosts better than other T helper (Th) cells. SAP-deficient Tfh-like cells appeared virtually indistinguishable from wild-type, yet failed to support GCs in vivo. Interestingly, both Tfh-like and in vivo-derived Tfh cells could produce effector cytokines in response to polarizing conditions. Moreover, Th1, Th2, and Th17 cells could be reprogrammed to obtain Tfh cell characteristics. ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3, and Rorc in Tfh-like and ex vivo Tfh cells and on Bcl6 in non-Tfh cells, supporting the concept of plasticity between Tfh and other Th cell populations

    The DNA Methylation Inhibitor Zebularine Controls CD4(+) T Cell Mediated Intraocular Inflammation

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    CD4+ T cell mediated uveitis is conventionally treated with systemic immunosuppressive agents, including corticosteroids and biologics targeting key inflammatory cytokines. However, their long-term utility is limited due to various side effects. Here, we investigated whether DNA methylation inhibitor zebularine can target CD4+ T cells and control intraocular inflammation. Our results showed that zebularine restrained the expression of inflammatory cytokines IFN-Ī³ and IL-17 in both human and murine CD4+ T cells in vitro. Importantly, it also significantly alleviated intraocular inflammation and retinal tissue damage in the murine experimental autoimmune uveitis (EAU) model in vivo, suggesting that the DNA methylation inhibitor zebularine is a candidate new therapeutic agent for uveitis

    Microstructural and Rheological Transitions in Bacterial Biofilms

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    Abstract Biofilms are aggregated bacterial communities structured within an extracellular matrix (ECM). ECM controls biofilm architecture and confers mechanical resistance against shear forces. From a physical perspective, biofilms can be described as colloidal gels, where bacterial cells are analogous to colloidal particles distributed in the polymeric ECM. However, the influence of the ECM in altering the cellular packing fraction (Ļ•) and the resulting viscoelastic behavior of biofilm remains unexplored. Using biofilms of Pantoea sp. (WT) and its mutant (Ī”UDP), the correlation between biofilm structure and its viscoelastic response is investigated. Experiments show that the reduction of exopolysaccharide production in Ī”UDP biofilms corresponds with a sevenā€fold increase in Ļ•, resulting in a colloidal glassā€like structure. Consequently, the rheological signatures become altered, with the WT behaving like a weak gel, whilst the Ī”UDP displayed a glassā€like rheological signature. By coā€culturing the two strains, biofilm Ļ• is modulated which allows us to explore the structural changes and capture a change in viscoelastic response from a weak to a strong gel, and to a colloidal glassā€like state. The results reveal the role of exopolysaccharide in mediating a structural transition in biofilms and demonstrate a correlation between biofilm structure and viscoelasticĀ response

    Stochastic Assembly of Bacteria in Microwell Arrays Reveals the Importance of Confinement in Community Development

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    Citation: Hansen, R. H., Timm, A. C., Timm, C. M., Bible, A. N., Morrell-Falvey, J. L., Pelletier, D. A., . . . Retterer, S. T. (2016). Stochastic Assembly of Bacteria in Microwell Arrays Reveals the Importance of Confinement in Community Development. Plos One, 11(5), 18. doi:10.1371/journal.pone.0155080The structure and function of microbial communities is deeply influenced by the physical and chemical architecture of the local microenvironment and the abundance of its community members. The complexity of this natural parameter space has made characterization of the key drivers of community development difficult. In order to facilitate these characterizations, we have developed a microwell platform designed to screen microbial growth and interactions across a wide variety of physical and initial conditions. Assembly of microbial communities into microwells was achieved using a novel biofabrication method that exploits well feature sizes for control of innoculum levels. Wells with incrementally smaller size features created populations with increasingly larger variations in inoculum levels. This allowed for reproducible growth measurement in large (20 mu m diameter) wells, and screening for favorable growth conditions in small (5, 10 mu m diameter) wells. We demonstrate the utility of this approach for screening and discovery using 5 mu m wells to assemble P. aeruginosa colonies across a broad distribution of innoculum levels, and identify those conditions that promote the highest probability of survivial and growth under spatial confinement. Multi-member community assembly was also characterized to demonstrate the broad potential of this platform for studying the role of member abundance on microbial competition, mutualism and community succession

    Choosing how to choose : Institutional pressures affecting the adoption of personnel selection procedures

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    The gap between science and practice in personnel selection is an ongoing concern of human resource management. This paper takes OliverĀ“s framework of organizationsĀ“ strategic responses to institutional pressures as a basis for outlining the diverse economic and social demands that facilitate or inhibit the application of scientifically recommended selection procedures. Faced with a complex network of multiple requirements, practitioners make more diverse choices in response to any of these pressures than has previously been acknowledged in the scientific literature. Implications for the science-practitioner gap are discussed

    Regenerative tissue filler for breast conserving surgery and other soft tissue restoration and reconstruction needs

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    Complete removal of cancerous tissue and preservation of breast cosmesis with a single breast conserving surgery (BCS) is essential for surgeons. New and better options would allow them to more consistently achieve this goal and expand the number of women that receive this preferred therapy, while minimizing the need for re-excision and revision procedures or more aggressive surgical approaches (i.e., mastectomy). We have developed and evaluated a regenerative tissue filler that is applied as a liquid to defects during BCS prior to transitioning to a fibrillar collagen scaffold with soft tissue consistency. Using a porcine simulated BCS model, the collagen filler was shown to induce a regenerative healing response, characterized by rapid cellularization, vascularization, and progressive breast tissue neogenesis, including adipose tissue and mammary glands and ducts. Unlike conventional biomaterials, no foreign body response or inflammatory-mediated ā€œactiveā€ biodegradation was observed. The collagen filler also did not compromise simulated surgical re-excision, radiography, or ultrasonography procedures, features that are important for clinical translation. When post-BCS radiation was applied, the collagen filler and its associated tissue response were largely similar to non-irradiated conditions; however, as expected, healing was modestly slower. This in situ scaffold-forming collagen is easy to apply, conforms to patient-specific defects, and regenerates complex soft tissues in the absence of inflammation. It has significant translational potential as the first regenerative tissue filler for BCS as well as other soft tissue restoration and reconstruction needs

    Lineages, Sub-Lineages and Variants of Enterovirus 68 in Recent Outbreaks

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    Enterovirus 68 (EV68) was first isolated in 1962. Very few cases of EV68 infection were described over the ensuing 40 years. However, in the past few years, an increase in severe respiratory tract infections associated with EV68 has been reported. We identified two clusters of EV68 infection in South London, UK, one each in the autumn/winters of 2009 and 2010. Sequence comparison showed significant homology of the UK strains with those from other countries including the Netherlands, Japan and the Philippines, which reported EV68 outbreaks between 2008 and 2010. Phylogenetic analysis of all available VP1 sequences indicated the presence of two modern EV68 lineages. The 2010 UK strains belonged to lineage 2. Lineage 1 could be further divided into two sub-lineages: some Japanese and Dutch strains collected between 2004 and 2010 form a distinct sub-lineages (sub-lineage 1.1), whereas other strains from the UK, Japan, Netherlands and Philippines collected between 2008 and 2010 represent sub-lineage 1.2. The UK 2009 strains together with several Dutch and Japanese strains from 2009/2010 represents one variant (1.2.1), whereas those from the Philippines a second variant (1.2.2). Based on specific deletions and substitutions, we suggest rules for the assignment of lineages and sub-lineages. Molecular epidemiological analysis indicates rapid recent evolution of EV68 and this may explain the recent findings of a global resurgence of EV68. Continuous global monitoring of the clinical and molecular epidemiology of EV68 is recommended

    Mice lacking the CĪ² subunit of PKA are resistant to angiotensin II-induced cardiac hypertrophy and dysfunction

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    <p>Abstract</p> <p>Background</p> <p>PKA is a ubiquitous, multi-subunit cellular kinase that regulates a number of different physiological responses in response to cAMP, including metabolism, cell division, and cardiac function. Numerous studies have implicated altered PKA signaling in cardiac dysfunction. Recently, it has been shown that mice lacking the catalytic Ī² subunit of PKA (PKA CĪ²) are protected from age-related problems such as weight gain and enlarged livers, and we hypothesized that these mice might also be resistant to cardiomyopathy.</p> <p>Findings</p> <p>Angiotensin II (ang II) induced hypertension in both PKA CĪ² null mice and their WT littermates. However, PKA CĪ² null mice were resistant to a number of ang II-induced, cardiopathological effects observed in the WT mice, including hypertrophy, decreased diastolic performance, and enlarged left atria.</p> <p>Conclusion</p> <p>The CĪ² subunit of PKA plays an important role in angiotensin-induced cardiac dysfunction. The CĪ² null mouse highlights the potential of the PKA CĪ² subunit as a pharmaceutical target for hypertrophic cardiac disease.</p
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