Smc5/6 is required for repair at collapsed replication forks.

In eukaryotes, three pairs of structural-maintenance-of-chromosome (SMC) proteins are found in conserved multisubunit protein complexes required for chromosomal organization. Cohesin, the Smc1/3 complex, mediates sister chromatid cohesion while two condensin complexes containing Smc2/4 facilitate chromosome condensation. Smc5/6 scaffolds an essential complex required for homologous recombination repair. We have examined the response of smc6 mutants to the inhibition of DNA replication. We define homologous recombination-dependent and -independent functions for Smc6 during replication inhibition and provide evidence for a Rad60-independent function within S phase, in addition to a Rad60-dependent function following S phase. Both genetic and physical data show that when forks collapse (i.e., are not stabilized by the Cds1Chk2 checkpoint), Smc6 is required for the effective repair of resulting lesions but not for the recruitment of recombination proteins. We further demonstrate that when the Rad60-dependent, post-S-phase Smc6 function is compromised, the resulting recombination-dependent DNA intermediates that accumulate following release from replication arrest are not recognized by the G2/M checkpoint

Note on the derivative of the hyperbolic cotangent

In a letter to Nature (Ford G W and O'Connell R F 1996 Nature 380 113) we presented a formula for the derivative of the hyperbolic cotangent that differs from the standard one in the literature by an additional term proportional to the Dirac delta function. Since our letter was necessarily brief, shortly after its appearance we prepared a more extensive unpublished note giving a detailed explanation of our argument. Since this note has been referenced in a recent article (Estrada R and Fulling S A 2002 J. Phys. A: Math. Gen. 35 3079) we think it appropriate that it now appear in print. We have made no alteration to the original note

Smc5/6 maintains stalled replication forks in a recombination-competent conformation

The Smc5/6 structural maintenance of chromosomes complex is required for efficient homologous recombination (HR). Defects in Smc5/6 result in chromosome missegregation and fragmentation. By characterising two Schizosaccharomyces pombe smc6 mutants, we define two separate functions for Smc5/6 in HR. The first represents the previously described defect in processing recombination-dependent DNA intermediates when replication forks collapse, which leads to increased rDNA recombination. The second novel function defines Smc5/6 as a positive regulator of recombination in the rDNA and correlates mechanistically with a requirement to load RPA and Rad52 onto chromatin genome-wide when replication forks are stably stalled by nucleotide depletion. Rad52 is required for all HR repair, but Rad52 loading in response to replication fork stalling is unexpected and does not correlate with damage-induced foci. We propose that Smc5/6 is required to maintain stalled forks in a stable recombination-competent conformation primed for replication restart

Self reported aggravating activities do not demonstrate a consistent directional pattern in chronic non specific low back pain patients: An observational study

Question: Do the self-reported aggravating activities of chronic non-specific low back pain patients demonstrate a consistent directional pattern? Design: Cross-sectional observational study. Participants: 240 chronic non specific low back pain patients. Outcome measure: We invited experienced clinicians to classify each of the three self-nominated aggravating activities from the Patient Specific Functional Scale by the direction of lumbar spine movement. Patients were described as demonstrating a directional pattern if all nominated activities moved the spine into the same direction. Analyses were undertaken to determine if the proportion of patients demonstrating a directional pattern was greater than would be expected by chance. Results: In some patients, all tasks did move the spine into the same direction, but this proportion did not differ from chance (p = 0.328). There were no clinical or demographic differences between those who displayed a directional pattern and those who did not (all p > 0.05). Conclusion: Using patient self-reported aggravating activities we were unable to demonstrate the existence of a consistent pattern of adverse movement in patients with chronic non-specific low back pain

Response to Teladorsagia circumcincta infection in Scottish Blackface lambs with divergent phenotypes for nematode resistance

peer-reviewedThe objective of this study was to identify Scottish Blackface lambs that were at the extremes of the spectrum of resistance to gastrointestinal nematodes and characterise their response to an experimental nematode challenge. Lambs (n = 90) were monitored for faecal egg count (FEC) (2 samples from each of 2 independent natural infections). The most resistant (n = 10) and susceptible (n = 10) individuals were selected and challenged with 30,000 Teladorsagia circumcincta larvae (L3) at 9 months of age. Response to infection was monitored by measuring FEC, plasma pepsinogen, serum antibodies against nematode larval antigens and haematology profile, until necropsy at 71 days post infection. Worm burden, worm fecundity and the level of anti-nematode antibodies in abomasal mucosa were determined at necropsy. FEC was consistently higher in susceptible animals (P < 0.05), validating the selection method. Worm fecundity was significantly reduced in resistant animals (P = 0.03). There was also a significant correlation (r = 0.88; P < 0.001) between the number of adult worms and FEC at slaughter. There was no effect of phenotype (resistance/susceptibility) on plasma pepsinogen or on haematology profile. Phenotype had a significant effect on the level of anti-nematode IgA antibodies in serum (P < 0.01), reflecting a higher peak in resistant animals at day 7 post infection. It is concluded that significant variation in the response to gastrointestinal nematode challenge exists within the Scottish Blackface population with resistant animals displaying significantly lower FEC, lower worm fecundity and higher concentration of anti-nematode IgA antibodies in serum.Kathryn McRae was supported by a Teagasc Walsh fellowship and the Allan and Grace Kay Overseas Scholarship

A Note on Frame Dragging

The measurement of spin effects in general relativity has recently taken centre stage with the successfully launched Gravity Probe B experiment coming toward an end, coupled with recently reported measurements using laser ranging. Many accounts of these experiments have been in terms of frame-dragging. We point out that this terminology has given rise to much confusion and that a better description is in terms of spin-orbit and spin-spin effects. In particular, we point out that the de Sitter precession (which has been mesured to a high accuracy) is also a frame-dragging effect and provides an accurate benchmark measurement of spin-orbit effects which GPB needs to emulate

The PHASES Differential Astrometry Data Archive. I. Measurements and Description

The Palomar High-precision Astrometric Search for Exoplanet Systems (PHASES) monitored 51 sub-arcsecond binary systems to determine precision binary orbits, study the geometries of triple and quadruple star systems, and discover previously unknown faint astrometric companions as small as giant planets. PHASES measurements made with the Palomar Testbed Interferometer (PTI) from 2002 until PTI ceased normal operations in late 2008 are presented. Infrared differential photometry of several PHASES targets were measured with Keck Adaptive Optics and are presented.Comment: 33 pages emulateapj, Accepted to A

Laplace transform of spherical Bessel functions

We provide a simple analytic formula in terms of elementary functions for the Laplace transform j_{l}(p) of the spherical Bessel function than that appearing in the literature, and we show that any such integral transform is a polynomial of order l in the variable p with constant coefficients for the first l-1 powers, and with an inverse tangent function of argument 1/p as the coefficient of the power l. We apply this formula for the Laplace transform of the memory function related to the Langevin equation in a one-dimensional Debye model.Comment: 5 pages LATEX, no figures. Accepted 2002, Physica Script