Analysis of Single Locus Trajectories for Extracting In Vivo Chromatin Tethering Interactions

Is it possible to extract tethering forces applied on chromatin from the statistics of a single locus trajectories imaged in vivo? Chromatin fragments interact with many partners such as the nuclear membrane, other chromosomes or nuclear bodies, but the resulting forces cannot be directly measured in vivo. However, they impact chromatin dynamics and should be reflected in particular in the motion of a single locus. We present here a method based on polymer models and statistics of single trajectories to extract the force characteristics and in particular when they are generated by the gradient of a quadratic potential well. Using numerical simulations of a Rouse polymer and live cell imaging of the MAT-locus located on the yeast Saccharomyces cerevisiae chromosome III, we recover the amplitude and the distance between the observed and the interacting monomer. To conclude, the confined trajectories we observed in vivo reflect local interaction on chromatin

Common peroneal nerve palsy complicating knee dislocation and bicruciate ligaments tears

SummaryIntroductionThe occurrence rate of common peroneal nerve (CPN) palsy associated with knee dislocation or bicruciate ligament injury ranges from 10 to 40%. The present study sought first to describe the anatomic lesions encountered and their associated prognoses and second to recommend adequate treatment strategy based on a prospective multicenter observational series of knee ligament trauma cases.Material and methodsTwelve out of 67 knees treated for dislocation or bicruciate lesion presented associated CPN palsy: two females, 10 males; mean age, 32 years. Four sports injuries, three traffic accidents and five other etiologies led to seven complete dislocations and five bicruciate ruptures. Four cases involved associated popliteal artery laceration ischemia; one of the dislocations was open. Paralysis was total in eight cases and partial in four. There were two complete ruptures, three contusions with CPN in continuity stretch lesions and three macroscopically normal aspects.ResultsAt a minimum 1 year's follow-up, regardless of the initial surgical technique performed, recovery was complete in six cases, partial (in terms of motor function) in one and absent in five. Without specific CPN surgery, spontaneous recovery was partial in one case, complete in two and absent in none. Following simple emergency or secondary neurolysis, remission was total in four cases and absent in one. Three nerve grafts were all associated with non-recovery.DiscussionThe present results agree with literature findings. Palsy rates varied with trauma circumstances and departmental recruitment. Neurologic impairment was commensurate to ligamentary damages. The anatomic status of the CPN, subjected to violent traction by dislocation, was the most significant prognostic factor for neurologic recovery. In about 25% of dislocations, contusion-elongation over several centimeters was associated with as poor a prognosis as total rupture. CPN neurolysis is recommended when early clinical and EMG recovery fails to progress and/or in case of lateral ligamentary reconstruction. Possible peripheral nerve impairment needs to be included in the overall functional assessment of treatment for severe ligaments injuries and knee dislocation.Level of evidenceLevel IV, prospective study

Test de la vraisemblance entre deux motifs de points

Test de la vraisemblance entre deux motifs de point

Adaptation to DNA damage checkpoint in senescent telomerase-negative cells promotes genome instability.

In cells lacking telomerase, telomeres gradually shorten during each cell division to reach a critically short length, permanently activate the DNA damage checkpoint, and trigger replicative senescence. The increase in genome instability that occurs as a consequence may contribute to the early steps of tumorigenesis. However, because of the low frequency of mutations and the heterogeneity of telomere-induced senescence, the timing and mechanisms of genome instability increase remain elusive. Here, to capture early mutation events during replicative senescence, we used a combined microfluidic-based approach and live-cell imaging in yeast. We analyzed DNA damage checkpoint activation in consecutive cell divisions of individual cell lineages in telomerase-negative yeast cells and observed that prolonged checkpoint arrests occurred frequently in telomerase-negative lineages. Cells relied on the adaptation to the DNA damage pathway to bypass the prolonged checkpoint arrests, allowing further cell divisions despite the presence of unrepaired DNA damage. We demonstrate that the adaptation pathway is a major contributor to the genome instability induced during replicative senescence. Therefore, adaptation plays a critical role in shaping the dynamics of genome instability during replicative senescence