886 research outputs found
Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo.
Staphylococcus aureus is a commensal and major pathogen of humans and animals. Comparative genomics of S. aureus populations suggests that colonization of different host species is associated with carriage of mobile genetic elements (MGE), particularly bacteriophages and plasmids capable of encoding virulence, resistance, and immune evasion pathways. Antimicrobial-resistant S. aureus of livestock are a potential zoonotic threat to human health if they adapt to colonize humans efficiently. We utilized the technique of experimental evolution and co-colonized gnotobiotic piglets with both human- and pig-associated variants of the lineage clonal complex 398, and investigated growth and genetic changes over 16 days using whole genome sequencing. The human isolate survived co-colonization on piglets more efficiently than in vitro. During co-colonization, transfer of MGE from the pig to the human isolate was detected within 4 h. Extensive and repeated transfer of two bacteriophages and three plasmids resulted in colonization with isolates carrying a wide variety of mobilomes. Whole genome sequencing of progeny bacteria revealed no acquisition of core genome polymorphisms, highlighting the importance of MGE. Staphylococcus aureus bacteriophage recombination and integration into novel sites was detected experimentally for the first time. During colonization, clones coexisted and diversified rather than a single variant dominating. Unexpectedly, each piglet carried unique populations of bacterial variants, suggesting limited transmission of bacteria between piglets once colonized. Our data show that horizontal gene transfer occurs at very high frequency in vivo and significantly higher than that detectable in vitro
Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder
Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder
Astrobiological Complexity with Probabilistic Cellular Automata
Search for extraterrestrial life and intelligence constitutes one of the
major endeavors in science, but has yet been quantitatively modeled only rarely
and in a cursory and superficial fashion. We argue that probabilistic cellular
automata (PCA) represent the best quantitative framework for modeling
astrobiological history of the Milky Way and its Galactic Habitable Zone. The
relevant astrobiological parameters are to be modeled as the elements of the
input probability matrix for the PCA kernel. With the underlying simplicity of
the cellular automata constructs, this approach enables a quick analysis of
large and ambiguous input parameters' space. We perform a simple clustering
analysis of typical astrobiological histories and discuss the relevant boundary
conditions of practical importance for planning and guiding actual empirical
astrobiological and SETI projects. In addition to showing how the present
framework is adaptable to more complex situations and updated observational
databases from current and near-future space missions, we demonstrate how
numerical results could offer a cautious rationale for continuation of
practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo
In Vivo Comparison of Two Human Norovirus Surrogates for Testing Ethanol-Based Handrubs: The Mouse Chasing the Cat!
Human noroviruses (HuNoV), a major cause of acute gastroenteritis worldwide, cannot be readily cultured in the lab. Therefore, a feline calicivirus (FCV) is often used as its surrogate to, among other things, test alcohol-based handrubs (ABHR). The more recent laboratory culture of a mouse norovirus (MNV) provides an alternative. While MNV is closer to HuNoV in several respects, to date, no comparative testing of FCV and MNV survival and inactivation on human hands has been performed. This study was designed to address the knowledge gap. The rates of loss in viability during drying on hands were −1.91 and −1.65% per minute for FCV and MNV, respectively. When the contaminated skin was exposed for 20 s to either a commercial ABHR with 62% (v/v) ethanol or to 75% (v/v) ethanol in water, FCV infectivity was reduced by <1 log10 while that of MNV by nearly 2.8 log10. Extending the contact time to 30 s reduced the FCV titer by almost 2 log10 by both test substances and that of MNV by >3.5 log10 by the commercial ABHR while 75% ethanol did not show any noticeable improvement in activity as compared to the 20 s contact. An 80% (v/v) aqueous solution of ethanol gave only a 1.75 log10 reduction in MNV activity after 20 s. The results show significant differences in the ethanol susceptibility of FCV and MNV in contact times relevant to field use of ABHR and also that 62% ethanol was a more effective virucide than either 75% or 80% ethanol. These findings indicate the need for a review of the continuing use of FCV as a surrogate for HuNoV
Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare
Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums,
email) can be used to transfer digital information between healthcare professionals and young people who live
with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on
communication.
Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all
studies was undertaken.
Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five
categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony
(n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n =
10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the
intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication
technologies increased the frequency of contact between patient and healthcare professional. Findings were
inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was
available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver
interaction, self-care and metabolic transmission were reported for some communication technologies.
Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and
their effects on health difficult to determine. While communication technologies may increase the frequency of
contact between patient and health care professional, it remains unclear whether this results in improved
outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness
and cost effectiveness of increasing the use of communication technologies between young people and
healthcare professionals
Primordial Black Holes: sirens of the early Universe
Primordial Black Holes (PBHs) are, typically light, black holes which can
form in the early Universe. There are a number of formation mechanisms,
including the collapse of large density perturbations, cosmic string loops and
bubble collisions. The number of PBHs formed is tightly constrained by the
consequences of their evaporation and their lensing and dynamical effects.
Therefore PBHs are a powerful probe of the physics of the early Universe, in
particular models of inflation. They are also a potential cold dark matter
candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X.
Calmet (Springer, 2014
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
Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions
Phylogenomics of non-model ciliates based on transcriptomic analyses
© The Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. The attached file is the published version of the article
Recombination and positive selection identified in complete genome sequences of Japanese encephalitis virus
The mosquito-borne Japanese encephalitis virus (JEV) causes encephalitis in man but not in pigs. Complete genomes of a human, mosquito and pig isolate from outbreaks in 1982 and 1985 in Thailand were sequenced with the aim of identifying determinants of virulence that may explain the differences in outcomes of JEV infection between pigs and man. Phylogenetic analysis revealed that five of these isolates belonged to genotype I, but the 1982 mosquito isolate belonged to genotype III. There was no evidence of recombination among the Thai isolates, but there were phylogenetic signals suggestive of recombination in a 1994 Korean isolate (K94P05). Two sites of the genome under positive selection were identified: codons 996 and 2296 (amino acids 175 of the non-structural protein NS1 and 24 of NS4B, respectively). A structurally significant substitution was seen at NS4B position 24 of the human isolate compared with the mosquito and pig isolates from the 1985 outbreak in Thailand. The potential importance of the two sites in the evolution and ecology of JEV merits further investigation
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