1,774 research outputs found
Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase
Chk1 protein kinase maintains replication fork stability in metazoan cells in response to DNA damage and DNA replication inhibitors. Here, we have employed DNA fiber labeling to quantify, for the first time, the extent to which Chk1 maintains global replication fork rates during normal vertebrate S phase. We report that replication fork rates in Chk1¿/¿ chicken DT40 cells are on average half of those observed with wild-type cells. Similar results were observed if Chk1 was inhibited or depleted in wild-type DT40 cells or HeLa cells by incubation with Chk1 inhibitor or small interfering RNA. In addition, reduced rates of fork extension were observed with permeabilized Chk1¿/¿ cells in vitro. The requirement for Chk1 for high fork rates during normal S phase was not to suppress promiscuous homologous recombination at replication forks, because inhibition of Chk1 similarly slowed fork progression in XRCC3¿/¿ DT40 cells. Rather, we observed an increased number of replication fibers in Chk1¿/¿ cells in which the nascent strand is single-stranded, supporting the idea that slow global fork rates in unperturbed Chk1¿/¿ cells are associated with the accumulation of aberrant replication fork structure
Bundles of fibers useful for moving liquids at high fluxes and acquisition/distribution structures that use the bundles
The ability to transport body liquids in consumer products such as diapers, incontinents and feminine napkins is a key factor in their performance. This invention is designed to provide specific high fluxes (volume of liquid/(time*mass of polymer) of aqueous liquids in designated directions using bundles of new specially designed fibers. The key factors for the bundles are a high specific adhesion for the liquid of interest, a high specific volume of the bundle itself, and alignment of the fibers within the bundle. The invention includes novel liquid acquisition/distribution systems and absorbent products that include a liquid acquisition/distribution system which may incorporate the novel bundles of fibers
Innate Structure of DNA Foci Restricts the Mixing of DNA from Different Chromosome Territories
The distribution of chromatin within the mammalian nucleus is constrained by its organization into chromosome territories (CTs). However, recent studies have suggested that promiscuous intra- and inter-chromosomal interactions play fundamental roles in regulating chromatin function and so might define the spatial integrity of CTs. In order to test the extent of DNA mixing between CTs, DNA foci of individual CTs were labeled in living cells following incorporation of Alexa-488 and Cy-3 conjugated replication precursor analogues during consecutive cell cycles. Uniquely labeled chromatin domains, resolved following random mitotic segregation, were visualized as discrete structures with defined borders. At the level of resolution analysed, evidence for mixing of chromatin from adjacent domains was only apparent within the surface volumes where neighboring CTs touched. However, while less than 1% of the nuclear volume represented domains of inter-chromosomal mixing, the dynamic plasticity of DNA foci within individual CTs allows continual transformation of CT structure so that different domains of chromatin mixing evolve over time. Notably, chromatin mixing at the boundaries of adjacent CTs had little impact on the innate structural properties of DNA foci. However, when TSA was used to alter the extent of histone acetylation changes in chromatin correlated with increased chromatin mixing. We propose that DNA foci maintain a structural integrity that restricts widespread mixing of DNA and discuss how the potential to dynamically remodel genome organization might alter during cell differentiation
Establishment and mitotic stability of an extra-chromosomal mammalian replicon
<p>Abstract</p> <p>Background</p> <p>Basic functions of the eukaryotic nucleus, like transcription and replication, are regulated in a hierarchic fashion. It is assumed that epigenetic factors influence the efficiency and precision of these processes. In order to uncouple local and long-range epigenetic features we used an extra-chromosomal replicon to study the requirements for replication and segregation and compared its behavior to that of its integrated counterpart.</p> <p>Results</p> <p>The autonomous replicon replicates in all eukaryotic cells and is stably maintained in the absence of selection but, as other extra-chromosomal replicons, its establishment is very inefficient. We now show that following establishment the vector is stably associated with nuclear compartments involved in gene expression and chromosomal domains that replicate at the onset of S-phase. While the vector stays autonomous, its association with these compartments ensures the efficiency of replication and mitotic segregation in proliferating cells.</p> <p>Conclusion</p> <p>Using this novel minimal model system we demonstrate that relevant functions of the eukaryotic nucleus are strongly influenced by higher nuclear architecture. Furthermore our findings have relevance for the rational design of episomal vectors to be used for genetic modification of cells: in order to improve such constructs with respect to efficiency elements have to be identified which ensure that such constructs reach regions of the nucleus favorable for replication and transcription.</p
Screening of classical Casimir forces by electrolytes in semi-infinite geometries
We study the electrostatic Casimir effect and related phenomena in
equilibrium statistical mechanics of classical (non-quantum) charged fluids.
The prototype model consists of two identical dielectric slabs in empty space
(the pure Casimir effect) or in the presence of an electrolyte between the
slabs. In the latter case, it is generally believed that the long-ranged
Casimir force due to thermal fluctuations in the slabs is screened by the
electrolyte into some residual short-ranged force. The screening mechanism is
based on a "separation hypothesis": thermal fluctuations of the electrostatic
field in the slabs can be treated separately from the pure image effects of the
"inert" slabs on the electrolyte particles. In this paper, by using a
phenomenological approach under certain conditions, the separation hypothesis
is shown to be valid. The phenomenology is tested on a microscopic model in
which the conducting slabs and the electrolyte are modelled by the symmetric
Coulomb gases of point-like charges with different particle fugacities. The
model is solved in the high-temperature Debye-H\"uckel limit (in two and three
dimensions) and at the free fermion point of the Thirring representation of the
two-dimensional Coulomb gas. The Debye-H\"uckel theory of a Coulomb gas between
dielectric walls is also solved.Comment: 25 pages, 2 figure
Networked international politics
Network theory and methods are becoming increasingly used to study the causes and consequences of conflict. Network analysis allows researchers to develop a better understanding of the causal dynamics and structural geometry of the complex web of interdependencies at work in the onset, incidence, and diffusion of conflict and peace. This issue features new theoretical and empirical research demonstrating how properly accounting for networked interdependencies has profound implications for our understanding of the processes thought to be responsible for the conflict behavior of state and non-state actors. The contributors examine the variation in networks of states and transnational actors to explain outcomes related to international conflict and peace. They highlight how networked interdependencies affect conflict and cooperation in a broad range of areas at the center of international relations scholarship. It is helpful to distinguish between three uses of networks, namely: (1) as theoretical tools, (2) as measurement tools, and (3) as inferential tools. The introduction discusses each of these uses and shows how the contributions rely on one or several of them. Next, Monte Carlo simulations are used to illustrate one of the strengths of network analysis, namely that it helps researchers avoid biased inferences when the data generating process underlying the observed data contains extradyadic interdependencies. </jats:p
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