Control of Chromosome Segregation by the Aurora B Complex

Chromosome segregation during cell division requires spindle assembly around M-phase chromatin. In cells lacking centrosomes, such as those found in female meiosis, chromosomes themselves nucleate and stabilize microtubules in order to promote accurate spindle formation. Here we present a description of the composition and function of the vertebrate chromosomal passenger complex (CPC), known to include Incenp, Survivin, and the kinase Aurora B. We report the identification of Dasra A and Dasra B as two new components of the vertebrate CPC, and demonstrate that the CPC is required for chromatin-dependent spindle formation in Xenopus egg extracts. The failure of microtubule stabilization caused by depletion of the chromosomal passenger complex is rescued by codepletion of the microtubule-depolymerizing kinesin MCAK, whose activity is negatively regulated by Aurora B. We demonstrate that the Aurora B pathway is normally suppressed in the cytosol, but becomes activated by chromatin and centrosomes, leading to the phosphorylation of both histone H3 and the microtubule destabilizing protein Op18/Stathmin. Chromatin-mediated CPC activation and spindle assembly require Dasra protein-dependent chromatin binding by the CPC, but this function of Dasra proteins can be bypassed by adding anti-Incenp antibodies, which autonomously stimulate Aurora B pathway activity. Such inappropriate CPC activation leads to the formation of centrosomal spindles lacking chromosomes. These results demonstrate that Dasra proteins make the Aurora B pathway competent for chromatindependent activation, and provide a mechanism for the spatial regulation of spindle assembly

Magnetic Resonance Imaging of the Elbow: A Structured Approach

Context: The elbow is a complex joint and commonly injured in athletes. Evaluation of the elbow by magnetic resonance imaging (MRI) is an important adjunct to the physical examination. To facilitate accurate diagnosis, a concise structured approach to evaluation of the elbow by MRI is presented. Evidence Acquisition: A PubMed search was performed using the terms elbow and MR imaging. No limits were set on the range of years searched. Articles were reviewed for relevance with an emphasis of the MRI appearance of normal anatomy and common pathology of the elbow. Results: The spectrum of common elbow disorders varies from obvious acute fractures to chronic overuse injuries whose imaging manifestations can be subtle. MRI evaluation should include bones; lateral, medial, anterior, and posterior muscle groups; the ulnar and radial collateral ligaments; as well as nerves, synovium, and bursae. Special attention should be paid to the valgus extension overload syndrome and the MRI appearance of associated injuries when evaluating throwing athletes. Conclusion: MRI evaluation of the elbow should follow a structured approach to facilitate thoroughness, accuracy, and speed. Such an approach should cover bone, cartilage, muscle, tendons, ligaments, synovium, bursae, and nerves

The Chromosomal Passenger Complex Is Required for Chromatin-Induced Microtubule Stabilization and Spindle Assembly

AbstractIn cells lacking centrosomes, such as those found in female meiosis, chromosomes must nucleate and stabilize microtubules in order to form a bipolar spindle. Here we report the identification of Dasra A and Dasra B, two new components of the vertebrate chromosomal passenger complex containing Incenp, Survivin, and the kinase Aurora B, and demonstrate that this complex is required for chromatin-induced microtubule stabilization and spindle formation. The failure of microtubule stabilization caused by depletion of the chromosomal passenger complex was rescued by codepletion of the microtubule-depolymerizing kinesin MCAK, whose activity is negatively regulated by Aurora B. By contrast, we present evidence that the Ran-GTP pathway of chromatin-induced microtubule nucleation does not require the chromosomal passenger complex, indicating that the mechanisms of microtubule assembly by these two pathways are distinct. We propose that the chromosomal passenger complex regulates local MCAK activity to permit spindle formation via stabilization of chromatin-associated microtubules

G9a co-suppresses LINE1 elements in spermatogonia

BACKGROUND: Repression of retrotransposons is essential for genome integrity and the development of germ cells. Among retrotransposons, the establishment of CpG DNA methylation and epigenetic silencing of LINE1 (L1) elements and the intracisternal A particle (IAP) endogenous retrovirus (ERV) is dependent upon the piRNA pathway during embryonic germ cell reprogramming. Furthermore, the Piwi protein Mili, guided by piRNAs, cleaves expressed L1 transcripts to post-transcriptionally enforce L1 silencing in meiotic cells. The loss of both DNA methylation and the Mili piRNA pathway does not affect L1 silencing in the mitotic spermatogonia where histone H3 lysine 9 dimethylation (H3K9me2) is postulated to co-repress these elements. RESULTS: Here we show that the histone H3 lysine 9 dimethyltransferase G9a co-suppresses L1 elements in spermatogonia. In the absence of both a functional piRNA pathway and L1 DNA methylation, G9a is both essential and sufficient to silence L1 elements. In contrast, H3K9me2 alone is insufficient to maintain IAP silencing in spermatogonia. The loss of all three repressive mechanisms has a major impact on spermatogonial populations inclusive of spermatogonial stem cells, with the loss of all germ cells observed in a high portion of seminiferous tubules. CONCLUSIONS: Our study identifies G9a-mediated H3K9me2 as a novel and important L1 repressive mechanism in the germ line. We also demonstrate fundamental differences in the requirements for the maintenance of L1 and IAP silencing during adult spermatogenesis, where H3K9me2 is sufficient to maintain L1 but not IAP silencing. Finally, we demonstrate that repression of retrotransposon activation in spermatogonia is important for the survival of this population and testicular homeostasis

Myoblast fusion confusion: the resolution begins

The fusion of muscle precursor cells is a required event for proper skeletal muscle development and regeneration. Numerous proteins have been implicated to function in myoblast fusion, however the majority are expressed in diverse tissues and regulate numerous cellular processes. How myoblast fusion is triggered and coordinated in a muscle-specific manner has remained a mystery for decades. Through the discovery of two muscle-specific fusion proteins, Myomaker and Myomerger/Minion, we are now primed to make significant advances in our knowledge of myoblast fusion. This article reviews the latest findings regarding the biology of Myomaker and Minion/Myomerger, places these findings in the context of known pathways in mammalian myoblast fusion, and highlights areas that require further investigation. As our understanding of myoblast fusion matures so does our potential ability to manipulate cell fusion for therapeutic purposes

MRI and Ultrasound of the Wrist Tendons

Wrist pain is common, and with diagnostic imaging often readily available, more patients are getting scans to find the etiology of pain. Both magnetic resonance imaging (MRI) and ultrasound are useful tools for evaluating the wrist. Ultrasound is a suitable imaging modality for the wrist tendons as it is fast and relatively inexpensive. Since the wrist tendons are superficial, the probe can be directly placed over them, thus acquiring excellent resolution and anatomic detail. MRI also provides high quality images of the tendons with the added bonus of detecting other abnormalities of the bones or cartilage which may not be apparent on ultrasound. In this paper we will review the normal anatomy and appearance of the tendons of the wrist and then present examples of common pathologies on MRI and ultrasound

Myoblast fusion confusion: the resolution begins

Abstract The fusion of muscle precursor cells is a required event for proper skeletal muscle development and regeneration. Numerous proteins have been implicated to function in myoblast fusion; however, the majority are expressed in diverse tissues and regulate numerous cellular processes. How myoblast fusion is triggered and coordinated in a muscle-specific manner has remained a mystery for decades. Through the discovery of two muscle-specific fusion proteins, Myomaker and Myomerger–Minion, we are now primed to make significant advances in our knowledge of myoblast fusion. This article reviews the latest findings regarding the biology of Myomaker and Minion–Myomerger, places these findings in the context of known pathways in mammalian myoblast fusion, and highlights areas that require further investigation. As our understanding of myoblast fusion matures so does our potential ability to manipulate cell fusion for therapeutic purposes

State of the Art: Imaging of Brown Adipose Tissue

The rates of diabetes, obesity, and metabolic disease have reached epidemic proportions worldwide. In recent years there has been renewed interest in combating these diseases not only by modifying energy intake and lifestyle factors, but also by promoting endogenous energy expenditure. This approach has largely been prompted by the recent recognition that brown adipose tissue (BAT)—long known to initiate heat production and energy expenditure in infants and hibernating mammals—also exists in adult humans. This landmark finding relied upon the use of clinical 18F-FDG-PET/CT and imaging techniques continue to play a critical and increasingly central role in understanding BAT physiology and function. Here, we review the origins of BAT imaging, discuss current preclinical and clinical strategies for imaging BAT, and discuss novel imaging methods that will provide crucial insight into metabolic disease and how it may be treated through modulation of BAT activity