424 research outputs found
On the relevance of mitochondrial fusions for the accumulation of mitochondrial deletion mutants: A modelling study
The molecular mechanisms underlying the aging process are still unclear, but the clonal accumulation of mitochondrial deletion mutants is one of the prime candidates. An important question for the mitochondrial theory of aging is to discover how defective organelles might be selected at the expense of wild-type mitochondria. We propose that mitochondrial fission and fusion events are of critical importance for resolving this apparent contradiction. We show that the occurrence of fusions removes the problems associated with the idea that smaller DNA molecules accumulate because they replicate in a shorter time – the survival of the tiny (SOT) hypothesis. Furthermore, stochastic simulations of mitochondrial replication, mutation and degradation show that two important experimental findings, namely the overall low mosaic pattern of oxidative phosphorylation (OXPHOS) impaired cells in old organisms and the distribution of deletion sizes, can be reproduced and explained by this hypothesis. Finally, we make predictions that can be tested experimentally to further verify our explanation for the age-related accumulation of mitochondrial deletion mutants
Mech Ageing Dev
Mitochondrial morphology is regulated in many cultured eukaryotic cells by fusion and fission of mitochondria. A tightly controlled balance between fission and fusion events is required to ensure normal mitochondrial and cellular functions. During ageing, mitochondria are undergoing significant changes on the functional and morphological level. The effect of ageing on fusion and fission of mitochondria and consequences of altered fission and fusion activity are still unknown although theoretical models on ageing consider the significance of these processes. Human umbilical vein endothelial cells (HUVECs) have been established as a cell culture model to follow mitochondrial activity and dysfunction during the ageing process. Mitochondria of old and postmitotic HUVECs showed distinct alterations in overall morphology and fine structure, and furthermore, loss of mitochondrial membrane potential. In parallel, a decrease of intact mitochondrial DNA (mtDNA) was observed. Fission and fusion activity of mitochondria were quantified in living cells. Mitochondria of old HUVECs showed a significant and equal decrease of both fusion and fission activity indicating that these processes are sensitive to ageing and could contribute to the accumulation of damaged mitochondria during ageing
Time evolution of the Partridge-Barton Model
The time evolution of the Partridge-Barton model in the presence of the
pleiotropic constraint and deleterious somatic mutations is exactly solved for
arbitrary fecundity in the context of a matricial formalism. Analytical
expressions for the time dependence of the mean survival probabilities are
derived. Using the fact that the asymptotic behavior for large time is
controlled by the largest matrix eigenvalue, we obtain the steady state values
for the mean survival probabilities and the Malthusian growth exponent. The
mean age of the population exhibits a power law decayment. Some Monte
Carlo simulations were also performed and they corroborated our theoretical
results.Comment: 10 pages, Latex, 1 postscript figure, published in Phys. Rev. E 61,
5664 (2000
Modelling contact mode and frequency of interactions with social network members using the multiple discrete–continuous extreme value model
Communication patterns are an integral component of activity patterns and the travel induced by these activities. The present study aims to understand the determinants of the communication patterns (by the modes face-to-face, phone, e-mail and SMS) between people and their social network members. The aim is for this to eventually provide further insights into travel behaviour for social and leisure purposes. A social network perspective brings value to the study and modelling of activity patterns since leisure activities are influenced not only by traditional trip measures such as time and cost but also motivated extensively by the people involved in the activity. By using a multiple discrete-continuous extreme value model (Bhat 2005), we can investigate the means of communication chosen to interact with a given social network member (multiple discrete choices) and the frequency of interaction by each mode (treated as continuous) at the same time. The model also allows us to investigate satiation effects for different modes of communication. Our findings show that in spite of people having increasingly geographically widespread networks and more diverse communication technologies, a strong underlying preference for face-to-face contact remains. In contrast with some of the existing work, we show that travel-related variables at the ego level are less important than specific social determinants which can be considered while making use of social network data
The Heumann-Hotzel model for aging revisited
Since its proposition in 1995, the Heumann-Hotzel model has remained as an
obscure model of biological aging. The main arguments used against it were its
apparent inability to describe populations with many age intervals and its
failure to prevent a population extinction when only deleterious mutations are
present. We find that with a simple and minor change in the model these
difficulties can be surmounted. Our numerical simulations show a plethora of
interesting features: the catastrophic senescence, the Gompertz law and that
postponing the reproduction increases the survival probability, as has already
been experimentally confirmed for the Drosophila fly.Comment: 11 pages, 5 figures, to be published in Phys. Rev.
Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress
<p>Abstract</p> <p>Background</p> <p>Eukaryotic cells have evolved various response mechanisms to counteract the deleterious consequences of oxidative stress. Among these processes, metabolic alterations seem to play an important role.</p> <p>Results</p> <p>We recently discovered that yeast cells with reduced activity of the key glycolytic enzyme triosephosphate isomerase exhibit an increased resistance to the thiol-oxidizing reagent diamide. Here we show that this phenotype is conserved in <it>Caenorhabditis elegans </it>and that the underlying mechanism is based on a redirection of the metabolic flux from glycolysis to the pentose phosphate pathway, altering the redox equilibrium of the cytoplasmic NADP(H) pool. Remarkably, another key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is known to be inactivated in response to various oxidant treatments, and we show that this provokes a similar redirection of the metabolic flux.</p> <p>Conclusion</p> <p>The naturally occurring inactivation of GAPDH functions as a metabolic switch for rerouting the carbohydrate flux to counteract oxidative stress. As a consequence, altering the homoeostasis of cytoplasmic metabolites is a fundamental mechanism for balancing the redox state of eukaryotic cells under stress conditions.</p
SkyMapper and the Southern Sky Survey
This paper presents the design and science goals for the SkyMapper telescope.
SkyMapper is a 1.3m telescope featuring a 5.7 square degree field-of-view
Cassegrain imager commissioned for the Australian National University's
Research School of Astronomy and Astrophysics. It is located at Siding Spring
Observatory, Coonabarabran, NSW, Australia and will see first light in late
2007. The imager possesses 16kx16k 0.5 arcsec pixels. The primary scientific
goal of the facility is to perform the Southern Sky Survey, a six colour and
multi-epoch (4 hour, 1 day, 1 week, 1 month, 1 year sampling) photometric
survey of the southerly 2pi steradians to g~23 mag. The survey will provide
photometry to better than 3% global accuracy and astrometry to better than 50
mas. Data will be supplied to the community as part of the Virtual Observatory
effort. The survey will take five years to complete
Virus Replication as a Phenotypic Version of Polynucleotide Evolution
In this paper we revisit and adapt to viral evolution an approach based on
the theory of branching process advanced by Demetrius, Schuster and Sigmund
("Polynucleotide evolution and branching processes", Bull. Math. Biol. 46
(1985) 239-262), in their study of polynucleotide evolution. By taking into
account beneficial effects we obtain a non-trivial multivariate generalization
of their single-type branching process model. Perturbative techniques allows us
to obtain analytical asymptotic expressions for the main global parameters of
the model which lead to the following rigorous results: (i) a new criterion for
"no sure extinction", (ii) a generalization and proof, for this particular
class of models, of the lethal mutagenesis criterion proposed by Bull,
Sanju\'an and Wilke ("Theory of lethal mutagenesis for viruses", J. Virology 18
(2007) 2930-2939), (iii) a new proposal for the notion of relaxation time with
a quantitative prescription for its evaluation, (iv) the quantitative
description of the evolution of the expected values in in four distinct
"stages": extinction threshold, lethal mutagenesis, stationary "equilibrium"
and transient. Finally, based on these quantitative results we are able to draw
some qualitative conclusions.Comment: 23 pages, 1 figure, 2 tables. arXiv admin note: substantial text
overlap with arXiv:1110.336
Interferometric imaging with the 32 element Murchison Wide-field Array
The Murchison Wide-field Array (MWA) is a low frequency radio telescope,
currently under construction, intended to search for the spectral signature of
the epoch of re-ionisation (EOR) and to probe the structure of the solar
corona. Sited in Western Australia, the full MWA will comprise 8192 dipoles
grouped into 512 tiles, and be capable of imaging the sky south of 40 degree
declination, from 80 MHz to 300 MHz with an instantaneous field of view that is
tens of degrees wide and a resolution of a few arcminutes. A 32-station
prototype of the MWA has been recently commissioned and a set of observations
taken that exercise the whole acquisition and processing pipeline. We present
Stokes I, Q, and U images from two ~4 hour integrations of a field 20 degrees
wide centered on Pictoris A. These images demonstrate the capacity and
stability of a real-time calibration and imaging technique employing the
weighted addition of warped snapshots to counter extreme wide field imaging
distortions.Comment: Accepted for publication in PASP. This is the draft before journal
typesetting corrections and proofs so does contain formatting and journal
style errors, also has with lower quality figures for space requirement
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