261 research outputs found
Identification of a novel type of spacer element required for imprinting in fission yeast
Asymmetrical segregation of differentiated sister chromatids is thought to be important for cellular differentiation in higher
eukaryotes. Similarly, in fission yeast, cellular differentiation involves the asymmetrical segregation of a chromosomal
imprint. This imprint has been shown to consist of two ribonucleotides that are incorporated into the DNA during laggingstrand
synthesis in response to a replication pause, but the underlying mechanism remains unknown. Here we present key
novel discoveries important for unravelling this process. Our data show that cis-acting sequences within the mat1 cassette
mediate pausing of replication forks at the proximity of the imprinting site, and the results suggest that this pause dictates
specific priming at the position of imprinting in a sequence-independent manner. Also, we identify a novel type of cis-acting
spacer region important for the imprinting process that affects where subsequent primers are put down after the
replication fork is released from the pause. Thus, our data suggest that the imprint is formed by ligation of a not-fullyprocessed
Okazaki fragment to the subsequent fragment. The presented work addresses how differentiated sister
chromatids are established during DNA replication through the involvement of replication barriers
Common trends in the critical behavior of the Ising and directed walk models
We consider layered two-dimensional Ising and directed walk models and show
that the two problems are inherently related. The information about the
zero-field thermodynamical properties of the Ising model is contained into the
transfer matrix of the directed walk. For several hierarchical and aperiodic
distributions of the couplings, critical exponents for the two problems are
obtained exactly through renormalization.Comment: 4 pages, RevTeX file + 1 figure, epsf needed. To be published in PR
Rearrangement of Retinogeniculate Projection Patterns after Eye-Specific Segregation in Mice
It has been of interest whether and when the rearrangement of neuronal circuits can be induced after projection patterns are formed during development. Earlier studies using cats reported that the rearrangement of retinogeniculate projections could be induced even after eye-specific segregation has occurred, but detailed and quantitative characterization of this rearrangement has been lacking. Here we delineate the structural changes of retinogeniculate projections in the C57BL/6 mouse in response to monocular enucleation (ME) after eye-specific segregation. When ME was performed after eye-specific segregation, rearrangement of retinogeniculate axons in the dorsal lateral geniculate nucleus (dLGN) was observed within 5 days. Although this rearrangement was observed both along the dorsomedial-ventrolateral and outer-inner axes in the dLGN, it occurred more rapidly along the outer-inner axis. We also examined the critical period for this rearrangement and found that the rearrangement became almost absent by the beginning of the critical period for ocular dominance plasticity in the primary visual cortex. Taken together, our findings serve as a framework for the assessment of phenotypes of genetically altered mouse strains as well as provide insights into the mechanisms underlying the rearrangement of retinogeniculate projections
Anomalous Diffusion in Aperiodic Environments
We study the Brownian motion of a classical particle in one-dimensional
inhomogeneous environments where the transition probabilities follow
quasiperiodic or aperiodic distributions. Exploiting an exact correspondence
with the transverse-field Ising model with inhomogeneous couplings we obtain
many new analytical results for the random walk problem. In the absence of
global bias the qualitative behavior of the diffusive motion of the particle
and the corresponding persistence probability strongly depend on the
fluctuation properties of the environment. In environments with bounded
fluctuations the particle shows normal diffusive motion and the diffusion
constant is simply related to the persistence probability. On the other hand in
a medium with unbounded fluctuations the diffusion is ultra-slow, the
displacement of the particle grows on logarithmic time scales. For the
borderline situation with marginal fluctuations both the diffusion exponent and
the persistence exponent are continuously varying functions of the
aperiodicity. Extensions of the results to disordered media and to higher
dimensions are also discussed.Comment: 11 pages, RevTe
Co-opetition models for governing professional football
In recent years, models for co-creating value in a business-to-business context have
often been examined with the aim of studying the strategies implemented by and
among organisations for competitive and co-operative purposes. The traditional
concepts of competition and co-operation between businesses have now evolved,
both in terms of the sector in which the businesses operate and in terms of the type
of goods they produce.
Many researchers have, in recent times, investigated the determinants that can
influence the way in which the model of co-opetition can be applied to the football
world. Research interest lies in the particular features of what makes a good football.
In this paper, the aim is to conduct an analysis of the rules governing the “football
system”, while also looking at the determinants of the demand function within
football entertainment. This entails applying to football match management the
co-opetition model, a recognised model that combines competition and co-operation
with the view of creating and distributing value. It can, therefore, be said that, for a
spectator, watching sport is an experience of high suspense, and this suspense, in turn,
depends upon the degree of uncertainty in the outcome. It follows that the rules
ensuring that both these elements can be satisfied are a fertile ground for co-operation
between clubs, as it is in the interest of all stakeholders to offer increasingly more
attractive football, in comparison with other competing products. Our end purpose is
to understand how co-opetition can be achieved within professional football
Hierarchy measure for complex networks
Nature, technology and society are full of complexity arising from the
intricate web of the interactions among the units of the related systems (e.g.,
proteins, computers, people). Consequently, one of the most successful recent
approaches to capturing the fundamental features of the structure and dynamics
of complex systems has been the investigation of the networks associated with
the above units (nodes) together with their relations (edges). Most complex
systems have an inherently hierarchical organization and, correspondingly, the
networks behind them also exhibit hierarchical features. Indeed, several papers
have been devoted to describing this essential aspect of networks, however,
without resulting in a widely accepted, converging concept concerning the
quantitative characterization of the level of their hierarchy. Here we develop
an approach and propose a quantity (measure) which is simple enough to be
widely applicable, reveals a number of universal features of the organization
of real-world networks and, as we demonstrate, is capable of capturing the
essential features of the structure and the degree of hierarchy in a complex
network. The measure we introduce is based on a generalization of the m-reach
centrality, which we first extend to directed/partially directed graphs. Then,
we define the global reaching centrality (GRC), which is the difference between
the maximum and the average value of the generalized reach centralities over
the network. We investigate the behavior of the GRC considering both a
synthetic model with an adjustable level of hierarchy and real networks.
Results for real networks show that our hierarchy measure is related to the
controllability of the given system. We also propose a visualization procedure
for large complex networks that can be used to obtain an overall qualitative
picture about the nature of their hierarchical structure.Comment: 29 pages, 9 figures, 4 table
Cdc45 Limits Replicon Usage from a Low Density of preRCs in Mammalian Cells
Little is known about mammalian preRC stoichiometry, the number of preRCs on chromosomes, and how this relates to replicon size and usage. We show here that, on average, each 100-kb of the mammalian genome contains a preRC composed of approximately one ORC hexamer, 4–5 MCM hexamers, and 2 Cdc6. Relative to these subunits, ∼0.35 total molecules of the pre-Initiation Complex factor Cdc45 are present. Thus, based on ORC availability, somatic cells contain ∼70,000 preRCs of this average total stoichiometry, although subunits may not be juxtaposed with each other. Except for ORC, the chromatin-bound complement of preRC subunits is even lower. Cdc45 is present at very low levels relative to the preRC subunits, but is highly stable, and the same limited number of stable Cdc45 molecules are present from the beginning of S-phase to its completion. Efforts to artificially increase Cdc45 levels through ectopic expression block cell growth. However, microinjection of excess purified Cdc45 into S-phase nuclei activates additional replication foci by three-fold, indicating that Cdc45 functions to activate dormant preRCs and is rate-limiting for somatic replicon usage. Paradoxically, although Cdc45 colocalizes in vivo with some MCM sites and is rate-limiting for DNA replication to occur, neither Cdc45 nor MCMs colocalize with active replication sites. Embryonic metazoan chromatin consists of small replicons that are used efficiently via an excess of preRC subunits. In contrast, somatic mammalian cells contain a low density of preRCs, each containing only a few MCMs that compete for limiting amounts of Cdc45. This provides a molecular explanation why, relative to embryonic replicon dynamics, somatic replicons are, on average, larger and origin efficiency tends to be lower. The stable, continuous, and rate-limiting nature of Cdc45 suggests that Cdc45 contributes to the staggering of replicon usage throughout S-phase, and that replicon activation requires reutilization of existing Cdc45 during S-phase
Critical dynamics in the evolution of stochastic strategies for the iterated Prisoner's Dilemma
The observed cooperation on the level of genes, cells, tissues, and
individuals has been the object of intense study by evolutionary biologists,
mainly because cooperation often flourishes in biological systems in apparent
contradiction to the selfish goal of survival inherent in Darwinian evolution.
In order to resolve this paradox, evolutionary game theory has focused on the
Prisoner's Dilemma (PD), which incorporates the essence of this conflict. Here,
we encode strategies for the iterated Prisoner's Dilemma (IPD) in terms of
conditional probabilities that represent the response of decision pathways
given previous plays. We find that if these stochastic strategies are encoded
as genes that undergo Darwinian evolution, the environmental conditions that
the strategies are adapting to determine the fixed point of the evolutionary
trajectory, which could be either cooperation or defection. A transition
between cooperative and defective attractors occurs as a function of different
parameters such a mutation rate, replacement rate, and memory, all of which
affect a player's ability to predict an opponent's behavior.Comment: 27 pages, including supplementary information. 5 figures, 4 suppl.
figures. Version accepted for publication in PLoS Comp. Bio
Controlled variations in stimulus similarity during learning determine visual discrimination capacity in freely moving mice
The mouse is receiving growing interest as a model organism for studying visual perception. However, little is known about how discrimination and learning interact to produce visual conditioned responses. Here, we adapted a two-alternative forced-choice visual discrimination task for mice and examined how training with equiprobable stimuli of varying similarity influenced conditioned response and discrimination performance as a function of learning. Our results indicate that the slope of the gradients in similarity during training determined the learning rate, the maximum performance and the threshold for successful discrimination. Moreover, the learning process obeyed an inverse relationship between discrimination performance and discriminative resolution, implying that sensitivity within a similarity range cannot be improved without sacrificing performance in another. Our study demonstrates how the interplay between discrimination and learning controls visual discrimination capacity and introduces a new training protocol with quantitative measures to study perceptual learning and visually-guided behavior in freely moving mice
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