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One critical step in RNA interference (RNAi) experiments is to design small interfering RNAs (siRNAs) that can greatly reduce the expression of the target transcripts, but not of other unintended targets. Although various statistical and computational approaches have been attempted, this remains a challenge facing RNAi researchers. Here, we present a new experimentally validated method for siRNA design. By analyzing public siRNA data and focusing on hyperfunctional siRNAs, we identified a set of sequence features as potency selection criteria to build an siRNA design algorithm with support vector machines. Additional bioinformatics filters were also included in the algorithm to increase RNAi specificity by reducing potential sequence cross-hybridization or microRNA-like effects. Independent validation experiments were performed, which indicated that the newly designed siRNAs have significantly improved performance, and worked effectively even at low concentrations. Furthermore, our cell-based studies demonstrated that the siRNA off-target effects were significantly reduced when the siRNAs were delivered into cells at the 3 nM concentration compared to 30 nM. Thus, the capability of our new design program to select highly potent siRNAs also renders increased RNAi specificity because these siRNAs can be used at a much lower concentration. The siRNA design web server is available at http://www5.appliedbiosystems.com/tools/siDesign/.

There are a variety of conditions that manifest not only in bone but also in skin. Bone and skin structures can share common embryologic origins, and genetic defects that occur early in cell differentiation may lead to disease in both organ systems. Alternatively, diseases of bone and skin may be caused by defects in genes that participate in directing or controlling both systems. Many diseases of bone and skin can manifest with atypical radiologic findings or mimic malignant bone lesions. Upon encountering such a disease process, a radiologist who is familiar with both aspects of the disorder and consequently looks for associated skin findings can greatly benefit the patient by making a definitive diagnosis. Similarly, a clinician who encounters suggestive skin lesions should be prompted to look for concomitant skeletal lesions. By synthesizing knowledge of bone and skin manifestations, radiologists and clinicians can help correctly diagnose a number of these disease processes, thereby helping patients avoid further, often nonspecific invasive workup and advancing patient care.

We present a case of lipoma arborescens of the knee in a 17-year-old man, discuss its characteristic imaging findings, and review the relevant differential diagnoses.

No abstract