Per chi? Quando il disagio è evidente. Applicazioni della tecnica della scrittura in popolazioni portatrici di sofferenza mentale o patologia somatica. In FrancoAngeli, Scrivere per pensare. La ritrascrizione dell'esperienza la promozione della salute e ricerca (2007 ed., pp. 119-122). Milano: Franco Solano.

The microtubule cytoskeleton is essential to cell morphogenesis. Growing microtubule plus ends have emerged as dynamic regulatory sites in which specialized proteins, called plus-end-binding proteins (+TIPs), bind and regulate the proper functioning of microtubules. However, the molecular mechanism of plus-end association by +TIPs and their ability to track the growing end are not well understood. Here we report the in vitro reconstitution of a minimal plus-end tracking system consisting of the three fission yeast proteins Mal3, Tip1 and the kinesin Tea2. Using time-lapse total internal reflection fluorescence microscopy, we show that the EB1 homologue Mal3 has an enhanced affinity for growing microtubule end structures as opposed to the microtubule lattice. This allows it to track growing microtubule ends autonomously by an end recognition mechanism. In addition, Mal3 acts as a factor that mediates loading of the processive motor Tea2 and its cargo, the Clip170 homologue Tip1, onto the microtubule lattice. The interaction of all three proteins is required for the selective tracking of growing microtubule plus ends by both Tea2 and Tip1. Our results dissect the collective interactions of the constituents of this plus-end tracking system and show how these interactions lead to the emergence of its dynamic behaviour. We expect that such in vitro reconstitutions will also be essential for the mechanistic dissection of other plus-end tracking systems.

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During cell division, microtubules are arranged in a large bipolar structure, the mitotic spindle, to segregate the duplicated chromosomes. Antiparallel microtubule overlaps in the spindle center are essential for establishing bipolarity and maintaining spindle stability throughout mitosis. In anaphase, this antiparallel microtubule array is tightly bundled forming the midzone, which serves as a hub for the recruitment of proteins essential for late mitotic events. The molecular mechanism of midzone formation and the control of its size are not understood. Using an in vitro reconstitution approach, we show here that PRC1 autonomously bundles antiparallel microtubules and recruits Xklp1, a kinesin-4, selectively to overlapping antiparallel microtubules. The processive motor Xklp1 controls overlap size by overlap length-dependent microtubule growth inhibition. Our results mechanistically explain how the two conserved, essential midzone proteins PRC1 and Xklp1 cooperate to constitute a minimal protein module capable of dynamically organizing the core structure of the central anaphase spindle.

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Context Mindfulness Based Cognitive Therapy (MBCT) is a group-based psychosocial intervention designed to enhance self-management of prodromal symptoms associated with depressive relapse. Objective To compare rates of relapse in remitted depressed patients receiving MBCT against maintenance antidepressant pharmacotherapy, the current standard of care Design Patients who met remission criteria following 8 months of algorithm informed antidepressant treatment were randomized to either: Maintenance Antidepressant Medication (M-ADM), MBCT or placebo (PLA) and were followed for 18 months. Setting Outpatient clinics at the Centre for Addiction and Mental Health, Toronto and St. Joseph’s Healthcare, Hamilton. Participants One hundred sixty patients aged 18 to 65 meeting DSM-IV for major depressive disorder with a minimum of 2 past episodes. Of these, 84 achieved remission (52.5%) and were assigned to one of the 3 study conditions. Interventions Remitted patients either discontinued their antidepressants and attended eight weekly group sessions of MBCT, continued on their therapeutic dose of antidepressant medication or discontinued active medication onto placebo. Main Outcome Measure Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression on Module A of the SCID. Results Intention to treat analyses revealed a significant interaction between the quality of acute phase remission and subsequent prevention of relapse in randomized patients (p = .03). Among unstable remitters (defined as 1 or more HRSD >7 during remission) patients in both MBCT and M-ADM showed a 73% decrease in hazard compared to PLA (p = .03), whereas for stable remitters (all HRSD ≤ 7 during remission) there were no group differences in survival. Findings remained significant after accounting for the effects of past depressive episodes on relapse. Conclusion For depressed patients who are unwilling or unable to tolerate long term maintenance antidepressant treatment, MBCT offers equivalent protection from relapse.

Branched actin networks–created by the Arp2/3 complex, capping protein, and a nucleation promoting factor– generate and transmit forces required for many cellular processes, but their response to force is poorly understood. To address this, we assembled branched actin networks in vitro from purified components and used simultaneous fluorescence and atomic force microscopy to quantify their molecular composition and material properties under various forces. Remarkably, mechanical loading of these self-assembling materials increases their density, power, and efficiency. Microscopically, increased density reflects increased filament number and altered geometry, but no change in average length. Macroscopically, increased density enhances network stiffness and resistance to mechanical failure beyond those of isotropic actin networks. These effects endow branched actin networks with memory of their mechanical history that shapes their material properties and motor activity. This work reveals intrinsic force feedback mechanisms by which mechanical resistance makes self-assembling actin networks stiffer, stronger, and more powerful.