112 research outputs found

    RSF Governs Silent Chromatin Formation via Histone H2Av Replacement

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    Human remodeling and spacing factor (RSF) consists of a heterodimer of Rsf-1 and hSNF2H, a counterpart of Drosophila ISWI. RSF possesses not only chromatin remodeling activity but also chromatin assembly activity in vitro. While no other single factor can execute the same activities as RSF, the biological significance of RSF remained unknown. To investigate the in vivo function of RSF, we generated a mutant allele of Drosophila Rsf-1 (dRsf-1). The dRsf-1 mutant behaved as a dominant suppressor of position effect variegation. In dRsf-1 mutant, the levels of histone H3K9 dimethylation and histone H2A variant H2Av were significantly reduced in an euchromatic region juxtaposed with heterochromatin. Furthermore, using both genetic and biochemical approaches, we demonstrate that dRsf-1 interacts with H2Av and the H2Av-exchanging machinery Tip60 complex. These results suggest that RSF contributes to histone H2Av replacement in the pathway of silent chromatin formation

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    Potential therapeutic approaches for modulating expression and accumulation of defective lamin A in laminopathies and age-related diseases

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    Low-kV coronary artery calcium scoring with tin filtration using a kV-independent reconstruction algorithm.

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    PURPOSE: To investigate the accuracy of Agatston scoring and potential for radiation dose reduction of a coronary artery calcium scoring (CACS) CT protocol at 100 kV with tin filtration (Sn100kV) and kV-independent iterative reconstruction, compared to standard 120 kV acquisitions. MATERIALS AND METHODS: With IRB approval and in HIPAA compliance, 114 patients (61.8 \ub1 9.6 years; 66 men) underwent CACS using a standard 120 kV protocol and an additional Sn100kV CACS scan. The two datasets were reconstructed using a medium sharp convolution algorithm and in addition the Sn100kV scans were reconstructed iteratively based on a kV-independent algorithm. Agatston scores and radiation dose values were compared between the Sn100kV and the standard 120 kV protocol. RESULTS: Median Agatston scores derived from the Sn100kV protocol with the kV-independent algorithm and the standard 120 kV were 21.4 (IQR, 0-173.8) and 24.7 (IQR, 0-171.1) respectively, with no significant differences (p=0.18). Agatston scores derived from the two different protocols had an excellent correlation (r = 0.99). The dose-length-product was 11.5 \ub1 4.1 mGy 7 cm using Sn100kV and 50.4 \ub1 24.9 mGy 7 cm using the standard 120 kV protocol (p < 0.01), resulting in a significantly lower (77%) effective dose at Sn100kV (0.16 \ub1 0.06 mSv vs. 0.71 \ub1 0.35 mSv, p < 0.01). Additionally, 99% of the patients were classified into the same risk category (0, 1-10, 11-100, 101-400, or >400) using the Sn100kV protocol. CONCLUSION: CACS at Sn100kV using the kV-independent iterative algorithm is feasible and provides high accuracy when compared to standard 120 kV scanning. Furthermore, radiation dose can be significantly reduced for this screening application in a priori healthy individuals

    European Association of Echocardiography recommendations for training, competence, and quality improvement in echocardiography

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    The main mission statement of the European Association of Echocardiography (EAE) is 'to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular ultrasound in Europe'. As competence and quality control issues are increasingly recognized by patients, physicians, and payers, the EAE has established recommendations for training, competence, and quality improvement in echocardiography. The purpose of this document is to provide the requirements for training and competence in echocardiography, to outline the principles of quality measurement, and to recommend a set of measures for improvement, with the ultimate goal of raising the standards of echocardiographic practice in Europe
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