150 research outputs found
Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review
Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood
Curved Tails in Polymerization-Based Bacterial Motility
The curved actin ``comet-tail'' of the bacterium Listeria monocytogenes is a
visually striking signature of actin polymerization-based motility. Similar
actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae,
the Vaccinia virus, and vesicles and microspheres in related in vitro systems.
We show that the torque required to produce the curvature in the tail can arise
from randomly placed actin filaments pushing the bacterium or particle. We find
that the curvature magnitude determines the number of actively pushing
filaments, independent of viscosity and of the molecular details of force
generation. The variation of the curvature with time can be used to infer the
dynamics of actin filaments at the bacterial surface.Comment: 8 pages, 2 figures, Latex2
Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus
Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al
Renormalization group and anomalous scaling in a simple model of passive scalar advection in compressible flow
Field theoretical renormalization group methods are applied to a simple model
of a passive scalar quantity advected by the Gaussian non-solenoidal
(``compressible'') velocity field with the covariance . Convective range anomalous scaling for the structure
functions and various pair correlators is established, and the corresponding
anomalous exponents are calculated to the order of the
expansion. These exponents are non-universal, as a result of the degeneracy of
the RG fixed point. In contrast to the case of a purely solenoidal velocity
field (Obukhov--Kraichnan model), the correlation functions in the case at hand
exhibit nontrivial dependence on both the IR and UV characteristic scales, and
the anomalous scaling appears already at the level of the pair correlator. The
powers of the scalar field without derivatives, whose critical dimensions
determine the anomalous exponents, exhibit multifractal behaviour. The exact
solution for the pair correlator is obtained; it is in agreement with the
result obtained within the expansion. The anomalous exponents for
passively advected magnetic fields are also presented in the first order of the
expansion.Comment: 31 pages, REVTEX file. More detailed discussion of the
one-dimensional case and comparison to the previous paper [20] are given;
references updated. Results and formulas unchange
Force spectroscopy in studying infection
Biophysical force spectroscopy tools - for example optical tweezers, magnetic
tweezers, atomic force microscopy, - have been used to study elastic,
mechanical, conformational and dynamic properties of single biological
specimens from single proteins to whole cells to reveal information not
accessible by ensemble average methods such as X-ray crystallography, mass
spectroscopy, gel electrophoresis and so on. Here we review the application of
these tools on a range of infection-related questions from antibody-inhibited
protein processivity to virus-cell adhesion. In each case we focus on how the
instrumental design tailored to the biological system in question translates
into the functionality suitable for that particular study. The unique insights
that force spectroscopy has gained to complement knowledge learned through
population averaging techniques in interrogating biomolecular details prove to
be instrumental in therapeutic innovations such as those in structure-based
drug design
Ebola virus disease: an update on post-exposure prophylaxis
The massive outbreak of Ebola virus disease in west Africa between 2013 and 2016 resulted in intense efforts to evaluate the efficacy of several specific countermeasures developed through years of preclinical work, including the first clinical trials for therapeutics and vaccines. In this Review, we discuss how the experience and data generated from that outbreak have helped to advance the understanding of the use of these countermeasures for post-exposure prophylaxis against Ebola virus infection. In future outbreaks, post-exposure prophylaxis could play an important part in reducing community transmission of Ebola virus by providing more immediate protection than does immunisation as well as providing additional protection for health-care workers who are inadvertently exposed over the course of their work. We propose provisional guidance for use of post-exposure prophylaxis in Ebola virus disease and identify the priorities for future preparedness and further research
Hysteresis, Avalanches, and Disorder Induced Critical Scaling: A Renormalization Group Approach
We study the zero temperature random field Ising model as a model for noise
and avalanches in hysteretic systems. Tuning the amount of disorder in the
system, we find an ordinary critical point with avalanches on all length
scales. Using a mapping to the pure Ising model, we Borel sum the
expansion to for the correlation length exponent. We sketch a
new method for directly calculating avalanche exponents, which we perform to
. Numerical exponents in 3, 4, and 5 dimensions are in good
agreement with the analytical predictions.Comment: 134 pages in REVTEX, plus 21 figures. The first two figures can be
obtained from the references quoted in their respective figure captions, the
remaining 19 figures are supplied separately in uuencoded forma
Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures
<p>Abstract</p> <p>Background</p> <p>Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg<sup>2+</sup>-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.</p> <p>Results</p> <p>Within 24 hrs of the insult regional specific changes in neuronal firing patterns were evident as: (i) a dramatic <it>reduction </it>in the ability of CA3 to generate firing; and (ii) a contrasting <it>increase </it>in the frequency and duration of synchronized neuronal firing events in CA1. Two distinct processes underlie the increased propensity of CA1 to generate synchronized burst firing; a lack of ability of the CA3 region to 'pace' CA1 resulting in an increased frequency of synchronized events; and a change in the 'intrinsic' properties limited to the CA1 region, which is responsible for increased event duration. Neuronal quantification using NeuN immunoflurescent staining and stereological confocal microscopy revealed no significant cell loss in hippocampal sub regions, suggesting that changes in the properties of neurons within this region were responsible for the KA-mediated excitability changes.</p> <p>Conclusion</p> <p>These results provide novel insight into adaptation of hippocampal circuits following excitotoxic injury. KA-mediated disruption of the interplay between CA3 and CA1 clearly increases the propensity to synchronized firing in CA1.</p
Decomposition cross-correlation for analysis of collagen matrix deformation by single smooth muscle cells
Microvascular remodeling is known to depend on cellular interactions with matrix tissue. However, it is difficult to study the role of specific cells or matrix elements in an in vivo setting. The aim of this study is to develop an automated technique that can be employed to obtain and analyze local collagen matrix remodeling by single smooth muscle cells. We combined a motorized microscopic setup and time-lapse video microscopy with a new cross-correlation based image analysis algorithm to enable automated recording of cell-induced matrix reorganization. This method rendered 60–90 single cell studies per experiment, for which collagen deformation over time could be automatically derived. Thus, the current setup offers a tool to systematically study different components active in matrix remodeling
Electron Tomography Reveals the Steps in Filovirus Budding
The filoviruses, Marburg and Ebola, are non-segmented negative-strand RNA viruses causing severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. The sequence of events that leads to release of filovirus particles from cells is poorly understood. Two contrasting mechanisms have been proposed, one proceeding via a “submarine-like” budding with the helical nucleocapsid emerging parallel to the plasma membrane, and the other via perpendicular “rocket-like” protrusion. Here we have infected cells with Marburg virus under BSL-4 containment conditions, and reconstructed the sequence of steps in the budding process in three dimensions using electron tomography of plastic-embedded cells. We find that highly infectious filamentous particles are released at early stages in infection. Budding proceeds via lateral association of intracellular nucleocapsid along its whole length with the plasma membrane, followed by rapid envelopment initiated at one end of the nucleocapsid, leading to a protruding intermediate. Scission results in local membrane instability at the rear of the virus. After prolonged infection, increased vesiculation of the plasma membrane correlates with changes in shape and infectivity of released viruses. Our observations demonstrate a cellular determinant of virus shape. They reconcile the contrasting models of filovirus budding and allow us to describe the sequence of events taking place during budding and release of Marburg virus. We propose that this represents a general sequence of events also followed by other filamentous and rod-shaped viruses
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