33 research outputs found
Single Molecule Studies of Recombinant Human α- and β-Cardiac Myosin to Elucidate Molecular Mechanism of Familial Hypertrophic and Dilated Cardiomyopathies
Discriminating between Cognitive and Supportive Group Therapies for Chronic Mental Illness
This descriptive and comparative study employed a Q-sort process to describe common factors of therapy in two group therapies for inpatients with chronic mental illness. While pharmacological treatments for chronic mental illness are prominent, there is growing evidence that cognitive therapy is also efficacious. Groups examined were part of a larger study comparing the added benefits of cognitive versus supportive group therapy to the treatment milieu. In general, items described the therapist’s attitudes and behaviors, the participants’ attitudes and behaviors, or the group interactions. Results present items that were most and least characteristic of each therapy and items that discriminate between the two modalities. Therapists in both groups demonstrated good therapy skills. However, the cognitive group was described as being more motivated and active than the supportive group, indicating that the groups differed in terms of common as well as specific factors of treatment
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The Spindle: Integrating Architecture and Mechanics across Scales
The spindle segregates chromosomes at cell division, and its task is a mechanical one. While we have a nearly complete list of spindle components, how their molecular-scale mechanics give rise to cellular-scale spindle architecture, mechanics, and function is not yet clear. Recent in vitro and in vivo measurements bring new levels of molecular and physical control and shed light on this question. Highlighting recent findings and open questions, we introduce the molecular force generators of the spindle, and discuss how they organize microtubules into diverse architectural modules and give rise to the emergent mechanics of the mammalian spindle. Throughout, we emphasize the breadth of space and time scales at play, and the feedback between spindle architecture, dynamics, and mechanics that drives robust function
Mapping Load-Bearing in the Mammalian Spindle Reveals Local Kinetochore Fiber Anchorage that Provides Mechanical Isolation and Redundancy
Active forces generated at kinetochores move chromosomes, and the dynamic spindle must robustly anchor kinetochore fibers (k-fibers) to bear this load. The mammalian spindle bears the load of chromosome movement far from poles, but we do not know where and how-physically and molecularly-this load distributes across the spindle. In part, this is because probing spindle mechanics in live cells is difficult. Yet answering this question is key to understanding how the spindle generates and responds to force and performs its diverse mechanical functions. Here, we map load-bearing across the mammalian spindle in space-time and dissect local anchorage mechanics and mechanism. To do so, we laser-ablate single k-fibers at different spindle locations and in different molecular backgrounds and quantify the immediate relaxation of chromosomes, k-fibers, and microtubule speckles. We find that load redistribution is locally confined in all directions: along the first 3-4 μm from kinetochores, scaling with k-fiber length, and laterally within ∼2 μm of k-fiber sides, without detectable load sharing between neighboring k-fibers. A phenomenological model suggests that dense, transient crosslinks to the spindle along k-fibers bear the load of chromosome movement but that these connections do not limit the timescale of spindle reorganization. The microtubule crosslinker NuMA is needed for the local load-bearing observed, whereas Eg5 and PRC1 are not detectably required, suggesting specialization in mechanical function. Together, the data and model suggest that NuMA-mediated crosslinks locally bear load, providing mechanical isolation and redundancy while allowing spindle fluidity. These features are well suited to support robust chromosome segregation