The protein-protein interactions required for assembly of the Tn3 resolution synapse

The site‐specific recombinase Tn3 resolvase initiates DNA strand exchange when two res recombination sites and six resolvase dimers interact to form a synapse. The detailed architecture of this intricate recombination machine remains unclear. We have clarified which of the potential dimer‐dimer interactions are required for synapsis and recombination, using a novel complementation strategy that exploits a previously uncharacterized resolvase from Bartonella bacilliformis (“Bart”). Tn3 and Bart resolvases recognize different DNA motifs, via diverged C‐terminal domains (CTDs). They also differ substantially at N‐terminal domain (NTD) surfaces involved in dimerization and synapse assembly. We designed NTD‐CTD hybrid proteins, and hybrid res sites containing both Tn3 and Bart dimer binding sites. Using these components in in vivo assays, we demonstrate that productive synapsis requires a specific “R ” interface involving resolvase NTDs at all three dimer‐binding sites in res . Synapses containing mixtures of wild‐type Tn3 and Bart resolvase NTD dimers are recombination‐defective, but activity can be restored by replacing patches of Tn3 resolvase R interface residues with Bart residues, or vice versa . We conclude that the Tn3 /Bart family synapse is assembled exclusively by R interactions between resolvase dimers, except for the one special dimer‐dimer interaction required for catalysis

Thermal Conductivity near H_c2 for spin-triplet superconducting States with line nodes in Sr_2RuO_4

We calculate the thermal conductivity kappa in magnetic fields near H_c2 for spin-triplet superconducting states with line nodes vertical and horizontal relative to the RuO_2-planes. The method for calculating the Green's functions takes into account the spatial variation of the order parameter and superconducting flow for the Abrikosov vortex lattice. For in-plane magnetic field we obtain variations of the in-plane kappa with two-fold symmetry as a function of rotation angle where the minima and maxima occur for field directions parallel and perpendicular to the heat flow. The amplitude of the variation decreases with increasing impurity scattering and temperature. At higher temperatures the minima and maxima of the variation are interchanged. Since the results for vertical and horizontal line nodes are almost the same we cannot say which of the two pairing models is more compatible with recent measurements of kappa in Sr_2RuO_4. The observed four-fold modulation of kappa in YBa_2Cu_3O_(7-\delta) is obtained for d-wave pairing by taking into account the particular shape of the Fermi surface and the finite temperature effect. The results for kappa for the f-wave pairing state with horizontal line nodes disagree in some respects with the measurements on UPt_3.Comment: 8 pages, 6 figures. To be published in Phys. Rev.

Detailed study of the ac susceptibility of Sr2RuO4 in oriented magnetic fields

We have investigated the ac susceptibility of the spin triplet superconductor Sr$_2$RuO$_4$ as a function of magnetic field in various directions at temperatures down to 60 mK. We have focused on the in-plane field configuration (polar angle $\theta \simeq 90^{\circ}$), which is a prerequisite for inducing multiple superconducting phases in Sr$_2$RuO$_4$. We have found that the previous attribution of a pronounced feature in the ac susceptibility to the second superconducting transition itself is not in accord with recent measurements of the thermal conductivity or of the specific heat. We propose that the pronounced feature is a consequence of additional involvement of vortex pinning originating from the second superconducting transition.Comment: Accepted for publication in Phys. Rev.

Magnetization plateaux in dimerized spin ladder arrays

We investigate the ground state magnetization plateaux appearing in spin 1/2 two-leg ladders built up from dimerized antiferromagnetic Heisenberg chains and dimerized zig-zag interchain couplings. Using both Abelian bosonization and Lanczos methods we find that the system yields rather unusual plateaux and exhibits massive and massless phases for specific choices or ``tuning'' of exchange interactions. The relevance of this behavior in the study of NH_4CuCl_3 is discussed.Comment: 9 pages, RevTeX, 11 postscript figure

Exercise therapy for knee osteoarthritis pain:how does it work? A study protocol for a randomised controlled trial

INTRODUCTION: Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA. METHODS AND ANALYSIS: The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study. ETHICS AND DISSEMINATION: This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians. TRIAL REGISTRATION NUMBER: NCT04362618.</p

Exercise therapy for knee osteoarthritis pain:how does it work? A study protocol for a randomised controlled trial

INTRODUCTION: Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA. METHODS AND ANALYSIS: The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study. ETHICS AND DISSEMINATION: This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians. TRIAL REGISTRATION NUMBER: NCT04362618.</p

Incorporating subject-specific geometry to compare metatarsal stress during running with different foot strike patterns

Stress fracture of the second metatarsal is a common and problematic injury for runners. The choice of foot strike pattern is known to affect external kinetics and kinematics but its effect on internal loading of the metatarsals is not well understood. Subject-specific models of the second metatarsal can be used to investigate internal loading in a non-invasive manner. This study aimed to compare second metatarsal stress between habitual rearfoot and non-rearfoot strikers during barefoot running, using a novel subject specific mathematical model, including accurate metatarsal geometry. Synchronised force and kinematic data were collected during barefoot overground running from 20 participants (12 rearfoot strikers). Stresses were calculated at the plantar and dorsal periphery of the midshaft of the metatarsal using a subject-specific beam theory model. Non-rearfoot strikers demonstrated greater external loading, bending moments and compressive forces than rearfoot strikers, but there were no differences in peak stresses between groups. Statistical parametric analysis revealed that non-rearfoot strikers had greater second metatarsal stresses during early stance but that there was no difference in peak stresses. This emphasises the importance of bone geometry when estimating bone stress and supports the suggestion that external forces should not be assumed to be representative of internal loading