715 research outputs found
Analysis of a Clostridium difficile PCR ribotype 078 100 kilobase island reveals the presence of a novel transposon, Tn6164.
Clostridium difficile is the main cause of antibiotic associated diarrhea. In the past decade, the number of C. difficile patients has increased dramatically, coinciding with the emergence of two PCR ribotypes 027 and 078. PCR ribotype 078 is also frequently found during C. difficile outbreaks in pigfarms. Previously, the genome of the PCR ribotype 078 strain M120, a human isolate, was described to contain a unique insert of 100 kilobases
Male X-chromosome mosaicism leading to carrier phenotype and inheritance of chronic granulomatous disease
We present the first description of a male with X-chromosome mosaicism who has clinical features of the X-linked CGD carrier state and passed a CYBB mutation to a daughter and subsequently affected grandson: clinicians should be aware of this possibility
P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments
Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes
Preventing crime in cooperation with the mental health care profession
Although major mental disorders do not have a central position in many criminological theories, there seems to be an evident relationship between these disorders and criminal behavior. In daily practice police officers and mental health care workers work jointly to prevent nuisance and crime and to keep the city livable. Examining the situations where the criminal justice system and mental health institutes are jointly involved to prevent crime, some pitfalls emerge that seem to threaten successful cooperation. There appear to be unrealistic expectations of the possibility to reduce the risk of reoffending by means of treatment and of the possibility to predict which offender poses a risk to society. Another complexity is the fact that both parties work from different backgrounds and pursue different goals. The way society and the criminal justice system deal with persons who are assumed to be a risk to the community because of a mental disorder demands a further investigation from a criminological perspective
BAKTRAK: Backtracking drifting objects using an iterative algorithm with a forward trajectory model
The task of determining the origin of a drifting object after it has been
located is highly complex due to the uncertainties in drift properties and
environmental forcing (wind, waves and surface currents). Usually the origin is
inferred by running a trajectory model (stochastic or deterministic) in
reverse. However, this approach has some severe drawbacks, most notably the
fact that many drifting objects go through nonlinear state changes underway
(e.g., evaporating oil or a capsizing lifeboat). This makes it difficult to
naively construct a reverse-time trajectory model which realistically predicts
the earliest possible time the object may have started drifting. We propose
instead a different approach where the original (forward) trajectory model is
kept unaltered while an iterative seeding and selection process allows us to
retain only those particles that end up within a certain time-space radius of
the observation. An iterative refinement process named BAKTRAK is employed
where those trajectories that do not make it to the goal are rejected and new
trajectories are spawned from successful trajectories. This allows the model to
be run in the forward direction to determine the point of origin of a drifting
object. The method is demonstrated using the Leeway stochastic trajectory model
for drifting objects due to its relative simplicity and the practical
importance of being able to identify the origin of drifting objects. However,
the methodology is general and even more applicable to oil drift trajectories,
drifting ships and hazardous material that exhibit non-linear state changes
such as evaporation, chemical weathering, capsizing or swamping. The
backtracking method is tested against the drift trajectory of a life raft and
is shown to predict closely the initial release position of the raft and its
subsequent trajectory.Comment: 28 pages, 8 figures, 2 table
The Distances of the Magellanic Clouds
The present status of our knowledge of the distances to the Magellanic Clouds
is evaluated from a post-Hipparcos perspective. After a brief summary of the
effects of structure, reddening, age and metallicity, the primary distance
indicators for the Large Magellanic Cloud are reviewed: The SN 1987A ring,
Cepheids, RR Lyraes, Mira variables, and Eclipsing Binaries. Distances derived
via these methods are weighted and combined to produce final "best" estimates
for the Magellanic Clouds distance moduli.Comment: Invited review article to appear in ``Post Hipparcos Cosmic
Candles'', F. Caputo & A. Heck (Eds.), Kluwer Academic Publ., Dordrecht, in
pres
Distances and ages of globular clusters using Hipparcos parallaxes of local subdwarfs
We discuss the impact of Population II and Globular Cluster (GCs) stars on
the derivation of the age of the Universe, and on the study of the formation
and early evolution of galaxies, our own in particular. The long-standing
problem of the actual distance scale to Population II stars and GCs is
addressed, and a variety of different methods commonly used to derive distances
to Population II stars are briefly reviewed. Emphasis is given to the
discussion of distances and ages for GCs derived using Hipparcos parallaxes of
local subdwarfs. Results obtained by different authors are slightly different,
depending on different assumptions about metallicity scale, reddenings, and
corrections for undetected binaries. These and other uncertainties present in
the method are discussed. Finally, we outline progress expected in the near
future.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles',
A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 22
pages including 3 tables and 2 postscript figures, uses Kluwer's crckapb.sty
LaTeX style file, enclose
Vaginal bacterium Prevotella timonensis turns protective Langerhans cells into HIV-1 reservoirs for virus dissemination
Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs) protect against mucosal HIV-1 infection via autophagy-mediated degradation of HIV-1. As LCs are in continuous contact with bacterial members of the vaginal microbiome, we investigated the impact of commensal and dysbiosis-associated vaginal (an)aerobic bacterial species on the antiviral function of LCs. Most of the tested bacteria did not affect the HIV-1 restrictive function of LCs. However, Prevotella timonensis induced a vast uptake of HIV-1 by vaginal LCs. Internalized virus remained infectious for days and uptake was unaffected by antiretroviral drugs. P. timonensis-exposed LCs efficiently transmitted HIV-1 to target cells both in vitro and ex vivo. Additionally, P. timonensis exposure enhanced uptake and transmission of the HIV-1 variants that establish infection after sexual transmission, the so-called Transmitted Founder variants. Our findings, therefore, suggest that P. timonensis might set the stage for enhanced HIV-1 susceptibility during vaginal dysbiosis and advocate targeted treatment of P. timonensis during bacterial vaginosis to limit HIV-1 infection
The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state
We introduce and analyze a minimal model of epigenetic silencing in budding
yeast, built upon known biomolecular interactions in the system. Doing so, we
identify the epigenetic marks essential for the bistability of epigenetic
states. The model explicitly incorporates two key chromatin marks, namely H4K16
acetylation and H3K79 methylation, and explores whether the presence of
multiple marks lead to a qualitatively different systems behavior. We find that
having both modifications is important for the robustness of epigenetic
silencing. Besides the silenced and transcriptionally active fate of chromatin,
our model leads to a novel state with bivalent (i.e., both active and
silencing) marks under certain perturbations (knock-out mutations, inhibition
or enhancement of enzymatic activity). The bivalent state appears under several
perturbations and is shown to result in patchy silencing. We also show that the
titration effect, owing to a limited supply of silencing proteins, can result
in counter-intuitive responses. The design principles of the silencing system
is systematically investigated and disparate experimental observations are
assessed within a single theoretical framework. Specifically, we discuss the
behavior of Sir protein recruitment, spreading and stability of silenced
regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the
controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page
Rationale and design of a proof-of-concept trial investigating the effect of uninterrupted perioperative (par)enteral nutrition on amino acid profile, cardiomyocytes structure, and cardiac perfusion and metabolism of patients undergoing coronary artery bypass grafting
<p>Abstract</p> <p>Background</p> <p>Malnutrition is very common in patients undergoing cardiac surgery. Malnutrition can change myocardial substrate utilization which can induce adverse effects on myocardial metabolism and function. We aim to investigate the hypothesis that there is a disturbed amino acids profile in the cardiac surgical patient which can be normalized by (par)enteral nutrition before, during and after surgery, subsequently improving cardiomyocyte structure, cardiac perfusion and glucose metabolism.</p> <p>Methods/Design</p> <p>This randomized controlled intervention study investigates the effect of uninterrupted perioperative (par)enteral nutrition on cardiac function in 48 patients undergoing coronary artery bypass grafting. Patients are given enteral nutrition (n = 16) or parenteral nutrition (n = 16), at least two days before, during, and two days after coronary artery bypass grafting, or are treated according to the standard guidelines (control) (n = 16). We will illustrate the effect of (par)enteral nutrition on differences in concentrations of amino acids and asymmetric dimethylarginine and in activity of dimethylarginine dimethylaminohydrolase and arginase in cardiac tissue and blood plasma. In addition, cardiomyocyte structure by histological, immuno-histochemical and ultrastructural analysis will be compared between the (par)enteral and control group. Furthermore, differences in cardiac perfusion and global left ventricular function and glucose metabolism, and their changes after coronary artery bypass grafting are evaluated by electrocardiography-gated myocardial perfusion scintigraphy and <sup>18</sup>F-fluorodeoxy-glucose positron emission tomography respectively. Finally, fat free mass is measured before and after intervention with bioelectrical impedance spectrometry in order to evaluate nutritional status.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2183">NTR2183</a></p
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