Avoiding chromosome pathology when replication forks collide

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Macmillan Publishers Limited.Chromosome duplication normally initiates through the assembly of replication fork complexes at defined origins1, 2. DNA synthesis by any one fork is thought to cease when it meets another travelling in the opposite direction, at which stage the replication machinery may simply dissociate before the nascent strands are finally ligated. But what actually happens is not clear. Here we present evidence consistent with the idea that every fork collision has the potential to threaten genomic integrity. In Escherichia coli this threat is kept at bay by RecG DNA translocase3 and by single-strand DNA exonucleases. Without RecG, replication initiates where forks meet through a replisome assembly mechanism normally associated with fork repair, replication restart and recombination4, 5, establishing new forks with the potential to sustain cell growth and division without an active origin. This potential is realized when roadblocks to fork progression are reduced or eliminated. It relies on the chromosome being circular, reinforcing the idea that replication initiation is triggered repeatedly by fork collision. The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit several origins to replicate each chromosome.THe MRC, the Leverhulme Trust, and the BBSRC

Functional opponency in working memory capacity predicts cognitive flexibility in problem solving.

Cognitive flexibility is a hallmark of individuals with higher working memory capacity (WMC). Yet, research demonstrates that higher WMC individuals are sometimes more likely to adopt rigid problem-solving approaches. The present research examines a novel account for these contradictory findings—that different WMC mechanisms interact in ways that both support and constrain cognitive flexibility. Across three studies, participants completed the water jug task—a problem-solving task requiring them to first establish and then break mental set using a complex strategy. Participants then completed measures targeting three WMC mechanisms: attention control, primary memory, and secondary memory. Study 1 demonstrated that primary memory and secondary memory predict breaking mental set in opposite directions. Study 2 replicated these findings while also demonstrating that attention control moderates these effects. Study 3 replicated these results using a less restrictive sampling procedure (i.e., participants were provided the complex strategy). The present research supports the proposed theory of functional opponency in WMC

The consequences of replicating in the wrong orientation: Bacterial chromosome duplication without an active replication origin

Chromosome replication is regulated in all organisms at the assembly stage of the replication machinery at specific origins. In Escherichia coli the DnaA initiator protein regulates the assembly of replication forks at oriC. This regulation can be undermined by defects in nucleic acid meta¬bolism. In cells lacking RNase HI replication initiates indepen¬dently of DnaA and oriC, presumably at persisting R-loops. A similar mechanism was assumed for origin-independent synthesis in cells lacking RecG. However, recently we suggested that this synthesis initiates at intermediates resulting from replication fork fusions. Here we present data suggesting that in cells lacking RecG or RNase HI origin-independent synthesis arises by different mechanisms, indicative of these two proteins having different roles in vivo. Our data support the idea that RNase HI processes R-loops, while RecG is required to process replication fork fusion intermediates. However, regardless of how origin-independent synthesis is initiated, a fraction of forks will proceed in an orientation opposite to normal. We show that the resulting head-on encounters with transcription threaten cell viability, especially if taking place in highly-transcribed areas. Thus, despite their different functions, RecG and RNase HI are both important factors for maintaining replication control and orientation. Their absence causes severe replication problems, highlighting the advantages of the normal chromosome arrangement, which exploits a single origin to control the number of forks and their orientation relative to transcription, and a defined termination area to contain fork fusions. Any changes to this arrangement endanger cell cycle control, chromosome dynamics and, ultimately, cell viability.This work was supported by the Royal Society (RG110414 to C.J.R.) and The Biotechnology and Biological Sciences Research Council (BB/K015729/1 to C.J.R.)

Enclothed Cognition and Controlled Attention during Insight Problem-Solving

Individual differences in working memory capacity (WMC) increase the ability, and tendency, to devote greater attentional control to a task—improving performance on a wide range of skills. In addition, recent research on enclothed cognition demonstrates that the situational influence of wearing a white lab coat increases controlled attention, due to the symbolic meaning and physical experience of wearing the coat. We examined whether these positive influences on attentional control lead to negative performance outcomes on insight problem-solving, a task thought to rely on associative processes that operate largely outside of explicit attentional control. Participants completed matchstick arithmetic problems while either wearing a white lab coat or in a no-coat control condition. Higher WMC was associated with lower insight problem-solving accuracy in the no-coat condition. In the coat condition, the insight problem-solving accuracy of lower WMC individuals dropped to the level of those higher in WMC. These results indicate that wearing a white lab coat led individuals to increase attentional control towards problem solving, hindering even lower WMC individuals from engaging in more diffuse, associative problem-solving processes, at which they otherwise excel. Trait and state factors known to increase controlled attention and improve performance on more attention-demanding tasks interact to hinder insight problem-solving

Internally damped, self-arresting vertical drop-weight impact test apparatus

A vertical dropped-weight impact test machine has a dropped-weight barrel vertically supported on upper and lower support brackets. The dropped-weight barrel is chambered to receive a dropped-weight assembly having a latch pin at its upper end, a damping unit in the middle, and a tup at its lower end. The tup is adapted for gathering data during impact testing. The latch pin releasably engages a latch pin coupling assembly. The latch pin coupling assembly is attached to a winch via a halyard for raising and lowering the dropped-weight assembly. The lower end of the dropped-weight barrel is provided with a bounce-back arresting mechanism which is activated by the descending passage of the dropped-weight assembly. After striking the specimen, the dropped-weight assembly rebounds vertically and is caught by the bounce-back arresting mechanism. The damping unit of the dropped-weight assembly serves to dissipate energy from the rebounding dropped-weight assembly and prevents the dropped-weight assembly from rebounding from the self-arresting mechanism

An exterior for the G\"{o}del spacetime

We match the vacuum, stationary, cylindrically symmetric solution of Einstein's field equations with $\Lambda$, in a form recently given by Santos, as an exterior to an infinite cylinder of dust cut out of a G\"{o}del universe. There are three cases, depending on the radius of the cylinder. Closed timelike curves are present in the exteriors of some of the solutions. There is a considerable similarity between the spacetimes investigated here and those of van Stockum referring to an infinite cylinder of rotating dust matched to vacuum, with $\Lambda=0$.Comment: 11 pages, LaTeX 2.09, no figures. Submitted to Classical and Quantum Gravit

Centrifugal force induced by relativistically rotating spheroids and cylinders

Starting from the gravitational potential of a Newtonian spheroidal shell we discuss electrically charged rotating prolate spheroidal shells in the Maxwell theory. In particular we consider two confocal charged shells which rotate oppositely in such a way that there is no magnetic field outside the outer shell. In the Einstein theory we solve the Ernst equations in the region where the long prolate spheroids are almost cylindrical; in equatorial regions the exact Lewis "rotating cylindrical" solution is so derived by a limiting procedure from a spatially bound system. In the second part we analyze two cylindrical shells rotating in opposite directions in such a way that the static Levi-Civita metric is produced outside and no angular momentum flux escapes to infinity. The rotation of the local inertial frames in flat space inside the inner cylinder is thus exhibited without any approximation or interpretational difficulties within this model. A test particle within the inner cylinder kept at rest with respect to axes that do not rotate as seen from infinity experiences a centrifugal force. Although the spacetime there is Minkowskian out to the inner cylinder nevertheless that space has been induced to rotate, so relative to the local inertial frame the particle is traversing a circular orbit.Comment: 12 pages, 2 figure

Internally damped, self-arresting vertical drop-weight apparatus

A vertical dropped-weight impact test machine has a dropped-weight barrel vertically supported on upper and lower support brackets. The dropped-weight barrel is chambered to receive a dropped-weight assembly having a latch pin at its upper end, a damping unit in the middle, and a tup at its lower end. The tup is adapted for gathering data during impact testing. The latch pin releasably engages a latch pin coupling assembly. The latch pin coupling assembly is attached to a winch via a halyard for raising and lowering the dropped-weight assembly. The lower end of the dropped-weight barrel is provided with a bounce-back arresting mechanism which is activated by the descending passage of the dropped-weight assembly. After striking the specimen, the dropped-weight assembly rebounds vertically and is caught by the bounce-back arresting mechanism. The damping unit of the dropped-weight assembly serves to dissipate energy from the rebounding dropped-weight assembly and prevents the dropped-weight assembly from rebounding from the self-arresting mechanism

The interior solution of axially symmetric, stationary and rigidly rotating dust configurations

It is shown that the interior solution of axially symmetric, stationary and rigidly rotating dust configurations is completely determined by the mass density along the axis of rotation. The particularly interesting case of a mass density, which is cylindrical symmetric in the interior of the dust configuration, is presented. Among other things, this proves the non-existence of homogeneous dust configurations.Comment: minor corrections to the published version, 10 page

Axisymmetric Stationary Solutions as Harmonic Maps

We present a method for generating exact solutions of Einstein equations in vacuum using harmonic maps, when the spacetime possesses two commutating Killing vectors. This method consists in writing the axisymmetric stationry Einstein equations in vacuum as a harmonic map which belongs to the group SL(2,R), and decomposing it in its harmonic "submaps". This method provides a natural classification of the solutions in classes (Weil's class, Lewis' class etc).Comment: 17 TeX pages, one table,( CINVESTAV- preprint 12/93