Dataset Information

Pac-man motility of kinetochores unleashed by laser microsurgery.

ABSTRACT: We report on experiments directly in living cells that reveal the regulation of kinetochore function by tension. X and Y sex chromosomes in crane fly (Nephrotoma suturalis) spermatocytes exhibit an atypical segregation mechanism in which each univalent maintains K-fibers to both poles. During anaphase, each maintains a leading fiber (which shortens) to one pole and a trailing fiber (which elongates) to the other. We used this intriguing behavior to study the motile states that X-Y kinetochores are able to support during anaphase. We used a laser microbeam to either sever a univalent along the plane of sister chromatid cohesion or knock out one of a univalent's two kinetochores to release one or both from the resistive influence of its sister's K-fiber. Released kinetochores with attached chromosome arms moved poleward at rates at least two times faster than normal. Furthermore, fluorescent speckle microscopy revealed that detached kinetochores converted their functional state from reverse pac-man to pac-man motility as a consequence of their release from mechanical tension. We conclude that kinetochores can exhibit pac-man motility, even though their normal behavior is dominated by traction fiber mechanics. Unleashing of kinetochore motility through loss of resistive force is further evidence for the emerging model that kinetochores are subject to tension-sensitive regulation.

SUBMITTER: LaFountain JR

PROVIDER: S-EPMC3418308 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pac-man motility of kinetochores unleashed by laser microsurgery.

LaFountain James R JR Cohan Christopher S CS Oldenbourg Rudolf R

Molecular biology of the cell 20120627 16

We report on experiments directly in living cells that reveal the regulation of kinetochore function by tension. X and Y sex chromosomes in crane fly (Nephrotoma suturalis) spermatocytes exhibit an atypical segregation mechanism in which each univalent maintains K-fibers to both poles. During anaphase, each maintains a leading fiber (which shortens) to one pole and a trailing fiber (which elongates) to the other. We used this intriguing behavior to study the motile states that X-Y kinetochores a ...[more]

PMID: 22740625

Similar Datasets

Project description:Transoral laser microsurgery (TLM) is an accepted and effective treatment strategy for supraglottic carcinomas. Early supraglottic carcinoma has excellent outcomes independently of the treatment approach. The role of TLM for the treatment of locally advanced tumors is debated. Particularly, the functional outcomes after TLM have to be proven by functional assessment of large cohorts of patients. This study analyzes the oncologic and functional outcomes after TLM for supraglottic carcinomas.Ninety-one patients with pT1-pT4a supraglottic carcinomas treated between January 2002 and December 2012 were analyzed. Distribution of tumors (UICC 2010) was 11 patients with pT1, 31 patients with pT2, 36 patients with pT3, and 13 patients with pT4a tumors. Node status was positive in 40 (43.6%) patients; 61 (67.1%) patients had stage III or IVa disease. Local control and survival were estimated using the Kaplan-Meier method. For the assessment of functional outcomes, the MD Anderson Dysphagia Inventory (MDADI), the Voice Handicap Index-10 (VHI-10), and the performance status scale for head and neck cancer [Performance Status Scale for Head and Neck (PSS-HN)] were used.The median age was 62 years (range, 33-88 years). Fourteen (15.4%) patients developed a local or locoregional recurrence. The 5-year local control rate and 5-year ultimate local control rate were 72 and 92%, respectively. The 5-year overall survival rate was 63%. Twelve (13.2%) patients needed temporary tracheostomy. Sixty-eight (74.0%) patients had a nasogastric feeding tube post-operatively. At 1-year post-operative follow-up, only three patients were PEG dependent. The median VHI-10 score was 35, the median MDADI composite score was 80, and the median score of the domain "normalcy of diet" in the PSS-HN was 91.The oncologic outcomes are comparable to the results of open surgery for early and advanced supraglottic carcinomas. Functional swallowing outcome is superior to open surgery and to concomitant chemoradiation. Patients treated with TLM perceive low levels of voice- and swallowing-related quality of life impairment.

Project description:Laser microsurgery is the current gold standard surgical technique for the treatment of selected diseases in delicate organs such as the larynx. However, the operations require large surgical expertise and dexterity, and face significant limitations imposed by available technology, such as the requirement for direct line of sight to the surgical field, restricted access, and direct manual control of the surgical instruments. To change this status quo, the European project μRALP pioneered research towards a complete redesign of current laser microsurgery systems, focusing on the development of robotic micro-technologies to enable endoscopic operations. This has fostered awareness and interest in this field, which presents a unique set of needs, requirements and constraints, leading to research and technological developments beyond μRALP and its research consortium. This paper reviews the achievements and key contributions of such research, providing an overview of the current state of the art in robot-assisted endoscopic laser microsurgery. The primary target application considered is phonomicrosurgery, which is a representative use case involving highly challenging microsurgical techniques for the treatment of glottic diseases. The paper starts by presenting the motivations and rationale for endoscopic laser microsurgery, which leads to the introduction of robotics as an enabling technology for improved surgical field accessibility, visualization and management. Then, research goals, achievements, and current state of different technologies that can build-up to an effective robotic system for endoscopic laser microsurgery are presented. This includes research in micro-robotic laser steering, flexible robotic endoscopes, augmented imaging, assistive surgeon-robot interfaces, and cognitive surgical systems. Innovations in each of these areas are shown to provide sizable progress towards more precise, safer and higher quality endoscopic laser microsurgeries. Yet, major impact is really expected from the full integration of such individual contributions into a complete clinical surgical robotic system, as illustrated in the end of this paper with a description of preliminary cadaver trials conducted with the integrated μRALP system. Overall, the contribution of this paper lays in outlining the current state of the art and open challenges in the area of robot-assisted endoscopic laser microsurgery, which has important clinical applications even beyond laryngology.

Dataset Information

Pac-man motility of kinetochores unleashed by laser microsurgery.

Publications

Pac-man motility of kinetochores unleashed by laser microsurgery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets