1,338 research outputs found

    Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning.

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    The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion.IMPORTANCEChlamydia trachomatis is an important cause of morbidity and a significant economic burden in the world. However, how Chlamydia develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered Chlamydia mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified microtubules around the inclusion and that Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi complex

    Nondestructive SEM for surface and subsurface wafer imaging

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    The scanning electron microscope (SEM) is considered as a tool for both failure analysis as well as device characterization. A survey is made of various operational SEM modes and their applicability to image processing methods on semiconductor devices

    Transcriptomes of parents identify parenting strategies and sexual conflict in a subsocial beetle

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    This work was funded by UK NERC grants to M.G.R. and A.J.M. an NERC studentship to D.J.P. the University of Georgia and a US NSF grant to A.J.M. and M.G.R.Parenting in the burying beetle Nicrophorus vespilloides is complex and, unusually, the sex and number of parents that can be present is flexible. Such flexibility is expected to involve specialized behaviour by the two sexes under biparental conditions. Here, we show that offspring fare equally well regardless of the sex or number of parents present. Comparing transcriptomes, we find a largely overlapping set of differentially expressed genes in both uniparental and biparental females and in uniparental males including vitellogenin, associated with reproduction, and takeout, influencing sex-specific mating and feeding behaviour. Gene expression in biparental males is similar to that in non-caring states. Thus, being ‘biparental’ in N. vespilloides describes the family social organization rather than the number of directly parenting individuals. There was no specialization; instead, in biparental families, direct male parental care appears to be limited with female behaviour unchanged. This should lead to strong sexual conflict.Publisher PDFPeer reviewe

    Dynamic fracture in carbon-fibre composites: Air-blast loading

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    In this study a response of a 2x2 twill weave T300 carbon fibre/epoxy composite flat plate specimen resultant air blast dynamic response observed in is examined, using a combination of non-invasive analysis techniques. The study investigates deformation and damage following air blasts with incident pressures of 0.4 MPa, 0.6 MPa and 0.8 MPa, and wave speeds between 650m/s and 950m/s. Digital image correlation was employed to obtain displacement data from the rear surfaces of the specimens during each experiment. 3D x-ray tomography was used to visualize the resultant internal damage within the samples. It was shown that the global deformation and transitions in curvature of each specimen appear to be similar with varying out-of-plane displacements. Damage was observed to propagate from the rear surface of the specimens through to the front surface as the air blast magnitude increased

    A Chandra Observation of Abell 13: Investigating the Origin of the Radio Relic

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    We present results from the Chandra X-ray observation of Abell 13, a galaxy cluster that contains an unusual noncentral radio source, also known as a radio relic. This is the first pointed X-ray observation of Abell 13, providing a more sensitive study of the properties of the X-ray gas. The X-ray emission from Abell 13 is extended to the northwest of the X-ray peak and shows substructure indicative of a recent merger event. The cluster X-ray emission is centered on the bright galaxy H of Slee et al. 2001. We find no evidence for a cooling flow in the cluster. A knot of excess X-ray emission is coincident with the other bright elliptical galaxy F. This knot of emission has properties similar to the enhanced emission associated with the large galaxies in the Coma cluster. With these Chandra data we are able to compare the properties of the hot X-ray gas with those of the radio relic from VLA data, to study the interaction of the X-ray gas with the radio emitting electrons. Our results suggest that the radio relic is associated with cooler gas in the cluster. We suggest two explanations for the coincidence of the cooler gas and radio source. First, the gas may have been uplifted by the radio relic from the cluster core. Alternatively, the relic and cool gas may have been displaced from the central galaxy during the cluster merger event.Comment: 11 pages, 9 figures, Accepted for Publication in the Astrophysical Journal, higher-resolution figures can be found at http://www.astro.virginia.edu/~amj3r/Abell13

    The Production of Antibody by Invading B Cells Is Required for the Clearance of Rabies Virus from the Central Nervous System

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    Every year over 50,000 people die from rabies worldwide, primarily due to the poor availability of rabies vaccine in developing countries. However, even when vaccines are available, human deaths from rabies occur if exposure to the causative virus is not recognized and vaccination is not sought in time. This is because rabies virus immunity induced by the natural infection or current vaccines is generally not effective at removing disease-causing rabies virus from brain tissues. Our studies provide insight into why this is the case and how vaccination can be changed so that the immune response can clear the virus from brain tissues. We show that the type of immune response induced by a live-attenuated rabies virus vaccine may be the key. In animal models, live-attenuated rabies virus vaccines are effective at delivering the immune cells capable of clearing the virus into CNS tissues and promote recovery from a rabies virus infection that has spread to the brain while conventional vaccines based on killed rabies virus do not. The production of rabies-specific antibody by B cells that invade the CNS tissues is important for complete elimination of the virus. We hypothesize that similar mechanisms may promote rabies virus clearance from individuals who are diagnosed after the virus has reached, but not extensively spread, through the CNS

    Type IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to \u3cem\u3eLegionella pneumophila\u3c/em\u3e

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    The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-κB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria
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