Purpose: To test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model.
Methods: Non-aqueous myelin protons have ultrashort Ts and are "invisible" with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T water signal so that the remaining signal is from the ultrashort T myelin component.
The balance between stem cell quiescence and proliferation in skeletal muscle is tightly controlled, but perturbed in a variety of disease states. Despite progress in identifying activators of stem cell proliferation, the niche factor(s) responsible for quiescence induction remain unclear. Here we report an in vivo imaging-based screen which identifies Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent inducer of muscle stem cell (MuSC, satellite cell) quiescence.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFAlthough recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, their function remains to be determined. Skeletal muscle development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process. Here we report the identification of Minion (microprotein inducer of fusion), a smORF encoding an essential skeletal muscle specific microprotein.
View Article and Find Full Text PDFThe tendons of the wrist are commonly symptomatic. They can be injured, infected, or inflamed. Magnetic resonance imaging and ultrasonography are useful tools for evaluating the wrist.
View Article and Find Full Text PDFThe 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 inducing endogenous energy expenditure. This approach has largely been stimulated by the recent recognition that brown adipose tissue (BAT)-long known to promote heat production and energy expenditure in infants and hibernating mammals-also exists in adult humans.
View Article and Find Full Text PDFProc Am Stat Assoc
August 2014
The Fligner and Verducci (1988) multistage model for rankings is modified to create the moving average maximum likelihood estimator (MAMLE), a locally smooth estimator that measures stage-wise agreement between two long ranked lists, and provides a stopping rule for the detection of the endpoint of agreement. An application of this MAMLE stopping rule to bivariate data set in tau-path order (Yu, Verducci and Blower (2011)) is discussed. Data from the National Cancer Institute measuring associations between gene expression and compound potency are studied using this application, providing insights into the length of the relationship between the variables.
View Article and Find Full Text PDFOsteoid osteoma is a relatively common, benign, painful tumor of bone. It is widely believed to run a course culminating in spontaneous regression. The tumor can usually be eliminated by excision or ablation, although it may recur locally.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFPurpose: Sodium fluoride PET (18F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered 18F-NaF and 18F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer 18F-NaF18/F-FDG PET/CT with CT alone for detection of osseous metastasis.
Patients And Methods: Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined 18F-NaF/18F-FDG PET/CT and diagnostic CT scans.
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.
View Article and Find Full Text PDFFor the problem of assessing initial agreement between two rankings of long lists, inference in the Fligner and Verducci (1988) multistage model for rankings is modified to provide a locally smooth estimator of stage-wise agreement. An extension to the case of overlapping but different sets of items in the two lists, and a stopping rule to identify the endpoint of agreement, are also provided. Simulations show that this approach performs very well under several conditions.
View Article and Find Full Text PDFWe propose an innovative approach to the problem recently posed by Hall and Schimek (2012): determining at what point the agreement between two rankings of a long list of items degenerates into noise. We modify the method of estimation in Fligner and Verducci's (1988) multistage model for rankings, from maximum likelihood of conditional agreement over a sample of rankings to a locally smooth estimator of agreement. Through simulations we show that this innovation performs very well under several conditions.
View Article and Find Full Text PDFEpigenetic gene silencing in eukaryotes is regulated in part by lysine methylation of the core histone proteins. While histone lysine methylation is known to control gene expression through the recruitment of modification-specific effector proteins, it remains unknown whether nonhistone chromatin proteins are targets for similar modification-recognition systems. Here we show that the histone H3 methyltransferase G9a contains a conserved methylation motif with marked sequence similarity to H3 itself.
View Article and Find Full Text PDFChromatin-induced spindle assembly depends on regulation of microtubule-depolymerizing proteins by the chromosomal passenger complex (CPC), consisting of Incenp, Survivin, Dasra (Borealin), and the kinase Aurora B, but the mechanism and significance of the spatial regulation of Aurora B activity remain unclear. Here, we show that the Aurora B pathway is suppressed in the cytoplasm of Xenopus egg extract by phosphatases, but that it becomes activated by chromatin via a Ran-independent mechanism. While spindle microtubule assembly normally requires Dasra-dependent chromatin binding of the CPC, this function of Dasra can be bypassed by clustering Aurora B-Incenp by using anti-Incenp antibodies, which stimulate autoactivation among bound complexes.
View Article and Find Full Text PDFIn 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.
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