Are redox changes a critical switch for mitotic progression?

Cell-cycle dependent redox changes result in increased protein oxidation in mitotic cells. We show that oxidative modifications of a conserved cysteine residue within Aurora A kinase (AURKA) can promote its activation during mitosis. Targeting redox-sensitive cysteine residues within AURKA may lead to the development of novel anti-cancer agents with improved clinical efficacy.

Redox priming promotes Aurora A activation during mitosis.

Cell cycle-dependent redox changes can mediate transient covalent modifications of cysteine thiols to modulate the activities of regulatory kinases and phosphatases. Our previously reported finding that protein cysteine oxidation is increased during mitosis relative to other cell cycle phases suggests that redox modifications could play prominent roles in regulating mitotic processes. The Aurora family of kinases and their downstream targets are key components of the cellular machinery that ensures the proper execution of mitosis and the accurate segregation of chromosomes to daughter cells.

Estimation and Observability Analysis of Human Motion on Lie Groups.

This article proposes a framework for human-pose estimation from the wearable sensors that rely on a Lie group representation to model the geometry of the human movement. Human body joints are modeled by matrix Lie groups, using special orthogonal groups SO(2) and SO(3) for joint pose and special Euclidean group SE(3) for base-link pose representation. To estimate the human joint pose, velocity, and acceleration, we develop the equations for employing the extended Kalman filter on Lie groups (LG-EKF) to explicitly account for the non-Euclidean geometry of the state space.

The Centrosome and the Primary Cilium: The Yin and Yang of a Hybrid Organelle.

Centrosomes and primary cilia are usually considered as distinct organelles, although both are assembled with the same evolutionary conserved, microtubule-based templates, the centrioles. Centrosomes serve as major microtubule- and actin cytoskeleton-organizing centers and are involved in a variety of intracellular processes, whereas primary cilia receive and transduce environmental signals to elicit cellular and organismal responses. Understanding the functional relationship between centrosomes and primary cilia is important because defects in both structures have been implicated in various diseases, including cancer.

Inertial measurement unit-based pose estimation: Analyzing and reducing sensitivity to sensor placement and body measures.

Introduction: Inertial measurement units have been proposed for automated pose estimation and exercise monitoring in clinical settings. However, many existing methods assume an extensive calibration procedure, which may not be realizable in clinical practice. In this study, an inertial measurement unit-based pose estimation method using extended Kalman filter and kinematic chain modeling is adapted for lower body pose estimation during clinical mobility tests such as the single leg squat, and the sensitivity to parameter calibration is investigated.

Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis.

Mitosis is controlled by reversible protein phosphorylation involving specific kinases and phosphatases. A handful of major mitotic protein kinases, such as the cyclin B-CDK1 complex, the Aurora kinases, and Polo-like kinase 1 (PLK1), cooperatively regulate distinct mitotic processes. Research has identified proteins and mechanisms that integrate these kinases into signaling cascades that guide essential mitotic events.

Classification-based Segmentation for Rehabilitation Exercise Monitoring.

Introduction: Exercise segmentation, the process of isolating individual repetitions from continuous time series measurement of human motion, is key to providing online feedback to patients during rehabilitation and enables the computation of useful metrics such as joint velocity and range of motion that are otherwise difficult to measure in the clinical setting.

Methods: This paper proposes a classifier-based approach, where the motion segmentation problem is formulated as a two-class classification problem, classifying between segment and non-segment points. The proposed approach does not require domain knowledge of the exercises and generalizes to groups of participants and exercises that were not part of the training set, allowing for more robustness in clinical applications.

Rhythmic Extended Kalman Filter for Gait Rehabilitation Motion Estimation and Segmentation.

This paper proposes a method to enable the use of non-intrusive, small, wearable, and wireless sensors to estimate the pose of the lower body during gait and other periodic motions and to extract objective performance measures useful for physiotherapy. The Rhythmic Extended Kalman Filter (Rhythmic-EKF) algorithm is developed to estimate the pose, learn an individualized model of periodic movement over time, and use the learned model to improve pose estimation. The proposed approach learns a canonical dynamical system model of the movement during online observation, which is used to accurately model the acceleration during pose estimation.

Assays to Study Mitotic Centrosome and Spindle Pole Assembly and Regulation.

Faithful chromosome segregation during cell division requires proper bipolar spindle assembly and critically depends on spindle pole integrity. In most animal cells, spindle poles form as the result of the concerted action of various factors operating in two independent pathways of microtubule assembly mediated by chromatin/RanGTP and by centrosomes. Mutation or deregulation of a number of spindle pole-organizing proteins has been linked to human diseases, including cancer and microcephaly.

Online tracking of the lower body joint angles using IMUs for gait rehabilitation.

An important field in physiotherapy is the rehabilitation of gait. A continuous assessment and progress tracking of a patient's ability to walk is of clinical interest. Unfortunately the tools available to the therapists are very time-consuming and subjective.

Human motion segmentation by data point classification.

Contemporary physiotherapy and rehabilitation practice uses subjective measures for motion evaluation and requires time-consuming supervision. Algorithms that can accurately segment patient movement would provide valuable data for progress tracking and on-line patient feedback. In this paper, we propose a two-class classifier approach to label each data point in the patient movement data as either a segment point or a non-segment point.

BRCA1 promotes unloading of the CMG helicase from a stalled DNA replication fork.

The tumor suppressor protein BRCA1 promotes homologous recombination (HR), a high-fidelity mechanism to repair DNA double-strand breaks (DSBs) that arise during normal replication and in response to DNA-damaging agents. Recent genetic experiments indicate that BRCA1 also performs an HR-independent function during the repair of DNA interstrand crosslinks (ICLs). Here we show that BRCA1 is required to unload the CMG helicase complex from chromatin after replication forks collide with an ICL.

The Cep192-organized aurora A-Plk1 cascade is essential for centrosome cycle and bipolar spindle assembly.

As cells enter mitosis, the two centrosomes separate and grow dramatically, each forming a nascent spindle pole that nucleates a radial array of microtubules. Centrosome growth (and associated microtubule nucleation surge), termed maturation, involves the recruitment of pericentriolar material components via an as-yet unknown mechanism. Here, we show that Cep192 binds Aurora A and Plk1, targets them to centrosomes in a pericentrin-dependent manner, and promotes sequential activation of both kinases via T-loop phosphorylation.

Mechanism of RAD51-dependent DNA interstrand cross-link repair.

DNA interstrand cross-links (ICLs) are toxic DNA lesions whose repair in S phase of eukaryotic cells is incompletely understood. In Xenopus egg extracts, ICL repair is initiated when two replication forks converge on the lesion. Dual incisions then create a DNA double-strand break (DSB) in one sister chromatid, whereas lesion bypass restores the other sister.

Aurora kinases and spindle assembly: variations on a common theme?

The Aurora A (AurA) serine/threonine kinase controls multiple aspects of cell division and plays a key role in centrosome maturation and bipolar spindle assembly. The pleiotropic functions of AurA depend on its interaction with several cofactors, the best known of which is TPX2. TPX2 targets AurA to spindle microtubules (MTs) and activates it, both allosterically and by protecting the activation loop (T-loop) of the kinase domain from dephosphorylation.

Centrosomal protein of 192 kDa (Cep192) promotes centrosome-driven spindle assembly by engaging in organelle-specific Aurora A activation.

Centrosomes are primary microtubule (MT)-organizing centers (MTOCs). During mitosis, they dramatically increase their size and MT-nucleating activity and participate in spindle assembly from spindle poles. These events require the serine/threonine kinase, Aurora A (AurA), and the centrosomal protein of 192 kDa (Cep192)/spindle defective 2 (Spd-2), but the underlying mechanism remains unclear.

The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly.

The heterodimeric tumor-suppressor complex BRCA1/BARD1 exhibits E3 ubiquitin ligase activity and participates in cell proliferation and chromosome stability control by incompletely defined mechanisms. Here we show that, in both mammalian cells and Xenopus egg extracts, BRCA1/BARD1 is required for mitotic spindle-pole assembly and for accumulation of TPX2, a major spindle organizer and Ran target, on spindle poles. This function is centrosome independent, operates downstream of Ran GTPase, and depends upon BRCA1/BARD1 E3 ubiquitin ligase activity.

The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA.

Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) mediates viral genome attachment to mitotic chromosomes. We find that N-terminal LANA docks onto chromosomes by binding nucleosomes through the folded region of histones H2A-H2B. The same LANA residues were required for both H2A-H2B binding and chromosome association.