984 research outputs found
Vestibular schwannoma: role of conservative management
Objective: To assess the outcome of conservative management of vestibular schwannoma.Study design: Observational study. Setting: Tertiary referral centre.Patients: Four hundred and thirty-six patients with vestibular schwannoma (490 tumours), including 327 sporadic tumours and 163 tumours in 109 patients with neurofibromatosis type two.Main outcome measures: The relationship of tumour growth to tumour size at presentation, and to certain demographic features.Results: The initial tumour size was significantly larger in the neurofibromatosis type two group (11 mm) than in the sporadic vestibular schwannoma group (5.1 mm). In both groups, 68 per cent of tumours did not grow during follow up (mean 3.6 years; range one to 14 years). The mean growth rate was 1.1 mm/year (range 0-15 mm/year) for sporadic tumours and 1.7 mm/year (range 0-18 mm/year) for neurofibromatosis type two tumours. The tumour growth rate correlated positively with tumour size in the sporadic tumour group, and correlated negatively with age in the neurofibromatosis type two group.Conclusion: Two-thirds of vestibular schwannomas did not grow. Radiological surveillance is an acceptable approach in carefully selected patients. Once a sporadic vestibular schwannoma reaches 2 cm in intracranial diameter, it is likely to continue growing. We do not recommend conservative management for sporadic tumours with an intracranial diameter of 1.5 cm or more. Vestibular schwannoma management is more complex in patients with neurofibromatosis type two
Boolean network model predicts cell cycle sequence of fission yeast
A Boolean network model of the cell-cycle regulatory network of fission yeast
(Schizosaccharomyces Pombe) is constructed solely on the basis of the known
biochemical interaction topology. Simulating the model in the computer,
faithfully reproduces the known sequence of regulatory activity patterns along
the cell cycle of the living cell. Contrary to existing differential equation
models, no parameters enter the model except the structure of the regulatory
circuitry. The dynamical properties of the model indicate that the biological
dynamical sequence is robustly implemented in the regulatory network, with the
biological stationary state G1 corresponding to the dominant attractor in state
space, and with the biological regulatory sequence being a strongly attractive
trajectory. Comparing the fission yeast cell-cycle model to a similar model of
the corresponding network in S. cerevisiae, a remarkable difference in
circuitry, as well as dynamics is observed. While the latter operates in a
strongly damped mode, driven by external excitation, the S. pombe network
represents an auto-excited system with external damping.Comment: 10 pages, 3 figure
The interplay of intrinsic and extrinsic bounded noises in genetic networks
After being considered as a nuisance to be filtered out, it became recently
clear that biochemical noise plays a complex role, often fully functional, for
a genetic network. The influence of intrinsic and extrinsic noises on genetic
networks has intensively been investigated in last ten years, though
contributions on the co-presence of both are sparse. Extrinsic noise is usually
modeled as an unbounded white or colored gaussian stochastic process, even
though realistic stochastic perturbations are clearly bounded. In this paper we
consider Gillespie-like stochastic models of nonlinear networks, i.e. the
intrinsic noise, where the model jump rates are affected by colored bounded
extrinsic noises synthesized by a suitable biochemical state-dependent Langevin
system. These systems are described by a master equation, and a simulation
algorithm to analyze them is derived. This new modeling paradigm should enlarge
the class of systems amenable at modeling.
We investigated the influence of both amplitude and autocorrelation time of a
extrinsic Sine-Wiener noise on: the Michaelis-Menten approximation of
noisy enzymatic reactions, which we show to be applicable also in co-presence
of both intrinsic and extrinsic noise, a model of enzymatic futile cycle
and a genetic toggle switch. In and we show that the
presence of a bounded extrinsic noise induces qualitative modifications in the
probability densities of the involved chemicals, where new modes emerge, thus
suggesting the possibile functional role of bounded noises
Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases
The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours
Correcting the Site Frequency Spectrum for Divergence-Based Ascertainment
Comparative genomics based on sequenced referenced genomes is essential to hypothesis generation and testing within population genetics. However, selection of candidate regions for further study on the basis of elevated or depressed divergence between species leads to a divergence-based ascertainment bias in the site frequency spectrum within selected candidate loci. Here, a method to correct this problem is developed that obtains maximum-likelihood estimates of the unascertained allele frequency distribution using numerical optimization. I show how divergence-based ascertainment may mimic the effects of natural selection and offer correction formulae for performing proper estimation into the strength of selection in candidate regions in a maximum-likelihood setting
Growth dynamics and the evolution of cooperation in microbial populations
Microbes providing public goods are widespread in nature despite running the
risk of being exploited by free-riders. However, the precise ecological factors
supporting cooperation are still puzzling. Following recent experiments, we
consider the role of population growth and the repetitive fragmentation of
populations into new colonies mimicking simple microbial life-cycles.
Individual-based modeling reveals that demographic fluctuations, which lead to
a large variance in the composition of colonies, promote cooperation. Biased by
population dynamics these fluctuations result in two qualitatively distinct
regimes of robust cooperation under repetitive fragmentation into groups.
First, if the level of cooperation exceeds a threshold, cooperators will take
over the whole population. Second, cooperators can also emerge from a single
mutant leading to a robust coexistence between cooperators and free-riders. We
find frequency and size of population bottlenecks, and growth dynamics to be
the major ecological factors determining the regimes and thereby the
evolutionary pathway towards cooperation.Comment: 26 pages, 6 figure
Cooperative secretions facilitate host range expansion in bacteria
The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses
Mobility promotes and jeopardizes biodiversity in rock-paper-scissors games
Biodiversity is essential to the viability of ecological systems. Species
diversity in ecosystems is promoted by cyclic, non-hierarchical interactions
among competing populations. Such non-transitive relations lead to an evolution
with central features represented by the `rock-paper-scissors' game, where rock
crushes scissors, scissors cut paper, and paper wraps rock. In combination with
spatial dispersal of static populations, this type of competition results in
the stable coexistence of all species and the long-term maintenance of
biodiversity. However, population mobility is a central feature of real
ecosystems: animals migrate, bacteria run and tumble. Here, we observe a
critical influence of mobility on species diversity. When mobility exceeds a
certain value, biodiversity is jeopardized and lost. In contrast, below this
critical threshold all subpopulations coexist and an entanglement of travelling
spiral waves forms in the course of temporal evolution. We establish that this
phenomenon is robust, it does not depend on the details of cyclic competition
or spatial environment. These findings have important implications for
maintenance and evolution of ecological systems and are relevant for the
formation and propagation of patterns in excitable media, such as chemical
kinetics or epidemic outbreaks.Comment: Final submitted version; the printed version can be found at
http://dx.doi.org/10.1038/nature06095 Supplementary movies are available at
http://www.theorie.physik.uni-muenchen.de/lsfrey/images_content/movie1.AVI
and
http://www.theorie.physik.uni-muenchen.de/lsfrey/images_content/movie2.AV
Programmability of Chemical Reaction Networks
Motivated by the intriguing complexity of biochemical circuitry within individual cells we study Stochastic Chemical Reaction Networks (SCRNs), a formal model that considers a set of chemical reactions acting on a finite number of molecules in a well-stirred solution according to standard chemical kinetics equations. SCRNs have been widely used for describing naturally occurring (bio)chemical systems, and with the advent of synthetic biology they become a promising language for the design of artificial biochemical circuits. Our interest here is the computational power of SCRNs and how they relate to more conventional models of computation. We survey known connections and give new connections between SCRNs and Boolean Logic Circuits, Vector Addition Systems, Petri Nets, Gate Implementability, Primitive Recursive Functions, Register Machines, Fractran, and Turing Machines. A theme to these investigations is the thin line between decidable and undecidable questions about SCRN behavior
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