MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport.

Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle transport behaviors, particularly pause/speed switching. As MAP7 is localized to branch sites, our results suggest a novel mechanism mediated by the dual interactions of MAP7 with microtubules and kinesin-1 in the precise control of microtubule-based transport during axon morphogenesis

The risk of misclassifying subjects within principal component based asset index.

The asset index is often used as a measure of socioeconomic status in empirical research as an explanatory variable or to control confounding. Principal component analysis (PCA) is frequently used to create the asset index. We conducted a simulation study to explore how accurately the principal component based asset index reflects the study subjects' actual poverty level, when the actual poverty level is generated by a simple factor analytic model. In the simulation study using the PC-based asset index, only 1% to 4% of subjects preserved their real position in a quintile scale of assets; between 44% to 82% of subjects were misclassified into the wrong asset quintile. If the PC-based asset index explained less than 30% of the total variance in the component variables, then we consistently observed more than 50% misclassification across quintiles of the index. The frequency of misclassification suggests that the PC-based asset index may not provide a valid measure of poverty level and should be used cautiously as a measure of socioeconomic status

Persistent Biomechanical Alterations After ACL Reconstruction Are Associated With Early Cartilage Matrix Changes Detected by Quantitative MR.

BackgroundThe effectiveness of anterior cruciate ligament (ACL) reconstruction in preventing early osteoarthritis is debated. Restoring the original biomechanics may potentially prevent degeneration, but apparent pathomechanisms have yet to be described. Newer quantitative magnetic resonance (qMR) imaging techniques, specifically T1ρ and T2, offer novel, noninvasive methods of visualizing and quantifying early cartilage degeneration.PurposeTo determine the tibiofemoral biomechanical alterations before and after ACL reconstruction using magnetic resonance imaging (MRI) and to evaluate the association between biomechanics and cartilage degeneration using T1ρ and T2.Study designCohort study; Level of evidence, 2.MethodsKnee MRIs of 51 individuals (mean age, 29.5 ± 8.4 years) with unilateral ACL injuries were obtained prior to surgery; 19 control subjects (mean age, 30.7 ± 5.3 years) were also scanned. Follow-up MRIs were obtained at 6 months and 1 year. Tibial position (TP), internal tibial rotation (ITR), and T1ρ and T2 were calculated using an in-house Matlab program. Student t tests, repeated measures, and regression models were used to compare differences between injured and uninjured sides, observe longitudinal changes, and evaluate correlations between TP, ITR, and T1ρ and T2.ResultsTP was significantly more anterior on the injured side at all time points (P < .001). ITR was significantly increased on the injured side prior to surgery (P = .033). At 1 year, a more anterior TP was associated with elevated T1ρ (P = .002) and T2 (P = .026) in the posterolateral tibia and with decreased T2 in the central lateral femur (P = .048); ITR was associated with increased T1ρ in the posteromedial femur (P = .009). ITR at 6 months was associated with increased T1ρ at 1 year in the posteromedial tibia (P = .029).ConclusionPersistent biomechanical alterations after ACL reconstruction are related to significant changes in cartilage T1ρ and T2 at 1 year postreconstruction. Longitudinal correlations between ITR and T1ρ suggest that these alterations may be indicative of future cartilage injury, leading to degeneration and osteoarthritis.Clinical relevanceNewer surgical techniques should be developed to eliminate the persistent anterior tibial translation commonly seen after ACL reconstruction. qMR will be a useful tool to evaluate the ability of these newer techniques to prevent cartilage changes