89 research outputs found
Stress induced telomere shortening: longer life with less mutations?
BACKGROUND: Mutations accumulate as a result of DNA damage and imperfect DNA repair machinery. In higher eukaryotes the accumulation and spread of mutations is limited in two primary ways: through p53-mediated programmed cell death and cellular senescence mediated by telomeres. Telomeres shorten at every cell division and cell stops dividing once the shortest telomere reaches a critical length. It has been shown that the rate of telomere attrition is accelerated when cells are exposed to DNA damaging agents. However the implications of this mechanism are not fully understood. RESULTS: With the help of in silico model we investigate the effect of genotoxic stress on telomere attrition and apoptosis in a population of non-identical replicating cells. When comparing the populations of cells with constant vs. stress-induced rate of telomere shortening we find that stress induced telomere shortening (SITS) increases longevity while reducing mutation rate. Interestingly, however, the effect takes place only when genotoxic stresses (e.g. reactive oxygen species due to metabolic activity) are distributed non-equally among cells. CONCLUSIONS: Our results for the first time show how non-equal distribution of metabolic load (and associated genotoxic stresses) combined with stress induced telomere shortening can delay aging and minimize mutations
Degree Landscapes in Scale-Free Networks
We generalize the degree-organizational view of real-world networks with
broad degree-distributions in a landscape analogue with mountains (high-degree
nodes) and valleys (low-degree nodes). For example, correlated degrees between
adjacent nodes corresponds to smooth landscapes (social networks), hierarchical
networks to one-mountain landscapes (the Internet), and degree-disassortative
networks without hierarchical features to rough landscapes with several
mountains. We also generate ridge landscapes to model networks organized under
constraints imposed by the space the networks are embedded in, associated to
spatial or, in molecular networks, to functional localization. To quantify the
topology, we here measure the widths of the mountains and the separation
between different mountains.Comment: 4 pages, 5 figure
Ecosystems with mutually exclusive interactions self-organize to a state of high diversity
Ecological systems comprise an astonishing diversity of species that
cooperate or compete with each other forming complex mutual dependencies. The
minimum requirements to maintain a large species diversity on long time scales
are in general unknown. Using lichen communities as an example, we propose a
model for the evolution of mutually excluding organisms that compete for space.
We suggest that chain-like or cyclic invasions involving three or more species
open for creation of spatially separated sub-populations that subsequently can
lead to increased diversity. In contrast to its non-spatial counterpart, our
model predicts robust co-existence of a large number of species, in accordance
with observations on lichen growth. It is demonstrated that large species
diversity can be obtained on evolutionary timescales, provided that
interactions between species have spatial constraints. In particular, a phase
transition to a sustainable state of high diversity is identified.Comment: 4 pages, 4 figure
Hierarchy Measures in Complex Networks
Using each node's degree as a proxy for its importance, the topological
hierarchy of a complex network is introduced and quantified. We propose a
simple dynamical process used to construct networks which are either maximally
or minimally hierarchical. Comparison with these extremal cases as well as with
random scale-free networks allows us to better understand hierarchical versus
modular features in several real-life complex networks. For random scale-free
topologies the extent of topological hierarchy is shown to smoothly decline
with -- the exponent of a degree distribution -- reaching its highest
possible value for and quickly approaching zero for .Comment: 4 pages, 4 figure
Circuit architecture explains functional similarity of bacterial heat shock responses
Heat shock response is a stress response to temperature changes and a
consecutive increase in amounts of unfolded proteins. To restore homeostasis,
cells upregulate chaperones facilitating protein folding by means of
transcription factors (TF). We here investigate two heat shock systems: one
characteristic to gram negative bacteria, mediated by transcriptional activator
sigma32 in E. coli, and another characteristic to gram positive bacteria,
mediated by transcriptional repressor HrcA in L. lactis. We construct simple
mathematical model of the two systems focusing on the negative feedbacks, where
free chaperons suppress sigma32 activation in the former, while they activate
HrcA repression in the latter. We demonstrate that both systems, in spite of
the difference at the TF regulation level, are capable of showing very similar
heat shock dynamics. We find that differences in regulation impose distinct
constrains on chaperone-TF binding affinities: the binding constant of free
sigma32 to chaperon DnaK, known to be in 100 nM range, set the lower limit of
amount of free chaperon that the system can sense the change at the heat shock,
while the binding affinity of HrcA to chaperon GroE set the upper limit and
have to be rather large extending into the micromolar range.Comment: 17 pages, 5 figure
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