2,725 research outputs found

    Microstructure-based Modeling of Primary Cilia Mechanics

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    A primary cilium, made of nine microtubule doublets enclosed in a cilium membrane, is a mechanosensing organelle that bends under an external mechanical load and sends an intracellular signal through transmembrane proteins activated by cilium bending. The nine microtubule doublets are the main load-bearing structural component, while the transmembrane proteins on the cilium membrane are the main sensing component. No distinction was made between these two components in all existing models, where the stress calculated from the structural component (nine microtubule doublets) was used to explain the sensing location, which may be totally misleading. For the first time, we developed a microstructure-based primary cilium model by considering these two components separately. First, we refined the analytical solution of bending an orthotropic cylindrical shell for individual microtubule, and obtained excellent agreement between finite element simulations and the theoretical predictions of a microtubule bending as a validation of the structural component in the model. Second, by integrating the cilium membrane with nine microtubule doublets and simulating the tip-anchored optical tweezer experiment on our computational model, we found that the microtubule doublets may twist significantly as the whole cilium bends. Third, besides being cilium-length-dependent, we found the mechanical properties of the cilium are also highly deformation-dependent. More important, we found that the cilium membrane near the base is not under pure in-plane tension or compression as previously thought, but has significant local bending stress. This challenges the traditional model of cilium mechanosensing, indicating that transmembrane proteins may be activated more by membrane curvature than membrane stretching. Finally, we incorporated imaging data of primary cilia into our microstructure-based cilium model, and found that comparing to the ideal model with uniform microtubule length, the imaging-informed model shows the nine microtubule doublets interact more evenly with the cilium membrane, and their contact locations can cause even higher bending curvature in the cilium membrane than near the base

    The zebrafish xenograft platform-A novel tool for modeling KSHV-associated diseases

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    Kaposi\u27s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic, but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the firs

    Dominance-related seasonal song production is unrelated to circulating testosterone in a subtropical songbird

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    AbstractCirculating testosterone (T) is widely considered to play a key role in the production of sexual displays by male vertebrates. While numerous studies support a role for circulating T in promoting the production of song in male birds, this understanding is based primarily on evidence from seasonally breeding northern temperate species, leaving it unclear whether this mechanism generalizes to other regions of the world. Here we investigate whether variation in circulating levels of T can explain the marked within- and among-individual variation in male song performance observed in a subtropical population of the year-round territorial white-browed sparrow weaver (Plocepasser mahali mahali). Our findings reveal that both circulating T and male song production peaked at a similar time point, halfway through the population-level breeding season. However, while dominant males were more likely to sing and sang for longer than subordinate males, within-group paired comparisons revealed no dominance-related differences in circulating T. Moreover, comparisons both among and within individual dominant males revealed that song duration, syllable rate and proportion of time spent singing were all unrelated to circulating T. Together, our findings suggest that natural variation in male song production, at least in this population of white-browed sparrow weavers, is achieved principally through mechanisms other than variation in circulating T concentration. More widely, our results are in line with the view that male song production is not exclusively regulated by gonadally synthesized steroids

    Carbon in Red Giants in Globular Clusters and Dwarf Spheroidal Galaxies

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    We present carbon abundances of red giants in Milky Way globular clusters and dwarf spheroidal galaxies (dSphs). Our sample includes measurements of carbon abundances for 154 giants in the clusters NGC 2419, M68, and M15 and 398 giants in the dSphs Sculptor, Fornax, Ursa Minor, and Draco. This sample doubles the number of dSph stars with measurements of [C/Fe]. The [C/Fe] ratio in the clusters decreases with increasing luminosity above log(L/L_sun) ~= 1.6, which can be explained by deep mixing in evolved giants. The same decrease is observed in dSphs, but the initial [C/Fe] of the dSph giants is not uniform. Stars in dSphs at lower metallicities have larger [C/Fe] ratios. We hypothesize that [C/Fe] (corrected to the initial carbon abundance) declines with increasing [Fe/H] due to the metallicity dependence of the carbon yield of asymptotic giant branch stars and due to the increasing importance of Type Ia supernovae at higher metallicities. We also identified 11 very carbon-rich giants (8 previously known) in three dSphs. However, our selection biases preclude a detailed comparison to the carbon-enhanced fraction of the Milky Way stellar halo. Nonetheless, the stars with [C/Fe] < +1 in dSphs follow a different [C/Fe] track with [Fe/H] than the halo stars. Specifically, [C/Fe] in dSphs begins to decline at lower [Fe/H] than in the halo. The difference in the metallicity of the [C/Fe] "knee" adds to the evidence from [alpha/Fe] distributions that the progenitors of the halo had a shorter timescale for chemical enrichment than the surviving dSphs.Comment: accepted to ApJ; 20 pages, 11 figures, 2 machine-readable table

    Primary Cilia Have a Length-Dependent Persistence Length

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    © 2019, The Author(s). The fluctuating position of an optically trapped cilium tip under untreated and Taxol-treated conditions was used to characterize mechanical properties of the cilium axoneme and its basal body by combining experimental, analytical,and computational tools. We provide, for the first time, evidence that the persistence length of a ciliary axoneme is length-dependent; longer cilia are stiffer than shorter cilia. We demonstrate that this apparent length dependence can be understood by a combination of modeling axonemal microtubules as anisotropic elastic shells and including actomyosin-driven stochastic basal body motion.Our results also demonstrate the possibility of using observable ciliary dynamics to probe interior cytoskeletal dynamics. It is hoped that our improved characterization of cilia will result in deeper understanding of the biological function of cellular flow sensing by this organelle

    Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non- Invasive Biomarker for Intestinal Inflammation

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    Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for low-grade inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1b, CXCL1, TNFa) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice

    A Chandra X-ray Study of Cygnus A - II. The Nucleus

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    We report Chandra ACIS and quasi-simultaneous RXTE observations of the nearby, powerful radio galaxy Cygnus A, with the present paper focusing on the properties of the active nucleus. In the Chandra observation, the hard (> a few keV) X-ray emission is spatially unresolved with a size \approxlt 1 arcsec (1.5 kpc, H_0 = 50 km s^-1 Mpc^-1) and coincides with the radio and near infrared nuclei. In contrast, the soft (< 2 keV) emission exhibits a bi-polar nebulosity that aligns with the optical bi-polar continuum and emission-line structures and approximately with the radio jet. In particular, the soft X-ray emission corresponds very well with the [O III] \lambda 5007 and H\alpha + [N II] \lambda\lambda 6548, 6583 nebulosity imaged with HST. At the location of the nucleus there is only weak soft X-ray emission, an effect that may be intrinsic or result from a dust lane that crosses the nucleus perpendicular to the source axis. The spectra of the various X-ray components have been obtained by simultaneous fits to the 6 detectors. The compact nucleus is detected to 100 keV and is well described by a heavily absorbed power law spectrum with \Gamma_h = 1.52^{+0.12}_{-0.12} (similar to other narrow line radio galaxies) and equivalent hydrogen column N_H (nuc) = 2.0^{+0.1}_{-0.2} \times 10^{23} cm^-2. (Abstract truncated).Comment: To be published in the Astrophysical Journal, v564 January 1, 2002 issue; 34 pages, 11 figures (1 color

    Incorporating security measures into the built environment

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    The protection of the built environment has been given increasing attention over recent years, with physical interventions being integrated into the built environment itself and an impetus on the role of those who are responsible for its design, construction and operation. Of particular note has been debate and behaviour surrounding the incorporation of security measures to specifically mitigate terrorist threats, as varying perceptions regarding obligations and incentives to do so have resulted in vulnerable places remaining unprotected. As part of on-going research into the security of the built environment, a three-year study into the protection of crowded places from terrorism has determined the factors that influence whether such measures are incorporated into built assets, in order to further understanding of the perceptions and reality behind decision making. Drawing on data obtained from interviews with 47 construction management and security professionals in the UK and USA, as well as observations during site visits and document analysis, a framework is put forward that presents the factors that influence whether security measures are incorporated, as well as the factors that influence the value of the measures themselves. The framework highlights the need to consider the incorporation of physical measures during the early design stages whilst also reconciling the requirements of such measures against those of other design criteria; to understand the intricacies surrounding risk mitigation within time and cost constraints, and to accrue maximum value. Such a framework, it is argued, would aid policy and key decision makers in co-ordinating their efforts and effectively protecting vulnerable places from the range of risks that the UK faces, thereby mitigating a range of natural hazards and major accidents, not just specific threats
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