High-throughput assessment of context-dependent effects of chromatin proteins.

BACKGROUND: Chromatin proteins control gene activity in a concerted manner. We developed a high-throughput assay to study the effects of the local chromatin environment on the regulatory activity of a protein of interest. The assay combines a previously reported multiplexing strategy based on barcoded randomly integrated reporters with Gal4-mediated tethering. We applied the assay to Drosophila heterochromatin protein 1a (HP1a), which is mostly known as a repressive protein but has also been linked to transcriptional activation. RESULTS: Recruitment to over 1000 genomic locations revealed that HP1a is a potent repressor able to silence even highly expressing reporter genes. However, the local chromatin context can modulate HP1a function. In pericentromeric regions, HP1a-induced repression was enhanced by twofold. In regions marked by a H3K36me3-rich chromatin signature, HP1a-dependent silencing was significantly decreased. We found no evidence for an activating function of HP1a in our experimental system. Furthermore, we did not observe stable transmission of repression over mitotic divisions after loss of targeted HP1a. CONCLUSIONS: The multiplexed tethered reporter assay should be applicable to a large number of chromatin proteins and will be a useful tool to dissect combinatorial regulatory interactions in chromatin.

Interventions for improving research productivity in clinical radiology.

The purpose of this study was to evaluate the effects of research promotion activities on overall quality and quantity of research output in a clinical department of a teaching tertiary care hospital. Simple research enhancing strategies including regular journal club, research hour, basic research skills training, hiring of research faculty, research awards, and annual research retreat and research board to increase research production were implemented in the Department of Radiology of a teaching hospital in Pakistan. A total of 77 papers were produced by the Department of Radiology before the intervention, which increased to 92 after the introduction of research initiatives. There was a significant increase in the overall proportion of publications in the international journals after the intervention (p < 0.001) with an increasing trend towards indexed journals (p < 0.001). The research enhancing interventions had a positive effect on increasing clinical research output by the Department of Radiology. Such interventions can also be replicated in other clinical departments to increase their research productivity.

Assessment of menisci and ligamentous injuries of the knee on magnetic resonance imaging: correlation with arthroscopy.

OBJECTIVE: To evaluate the validity of MRI, in the assessment of the meniscal and cruciate ligamenteous injuries of the knee joint and comparison with arthroscopic findings. METHODS: A one year prospective cross-sectional study from January 2006 to January 2007, was performed on 50 patients (32 males & 18 females) with knee injury presenting at the orthopedic unit of AKUH. The patients were referred to radiology department for MRI evaluation and arthroscopy. RESULTS: The sensitivity, specificity and accuracy for MRI of the menisci and ligaments were as follows: medial meniscus resulted in 100% sensitivity, 69.27% specificity, 90% PPV, 100% NPV and 92% accuracy: lateral meniscus resulted in 87.5% sensitivity, 88.23% specificity, 77% PPV, 93% NPV and 88% accuracy: anterior cruciate ligament resulted in 86.67% sensitivity, 91.43% specificity, 81% PPV, 94% NPV and 88% accuracy; posterior cruciate ligament resulted in 100% sensitivity, 95.83% specificity,50% PPV, 100 NPV and 96% accuracy. CONCLUSION: Magnetic resonance imaging is a good, accurate and non invasive modality for the assessment of menisci and ligamenteous injuries. It can be used as a first line investigation in patients with soft tissue trauma to knee.