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Articles by D. S Marks
Total Records ( 2 ) for D. S Marks
  S Sack , P Kahlert , L Bilodeau , L. A Pierard , P Lancellotti , V Legrand , J Bartunek , M Vanderheyden , R Hoffmann , P Schauerte , T Shiota , D. S Marks , R Erbel and S. G. Ellis

Background— We assessed the safety and feasibility of permanent implantation of a novel coronary sinus mitral repair device (PTMA, Viacor Inc).

Methods and Results— Symptomatic (New York Heart Association class 2 or 3) patients with primarily functional mitral regurgitation (MR) were included. A diagnostic PTMA procedure was performed in the coronary sinus venous continuity. MR was assessed and the PTMA device adjusted to optimize efficacy. If MR reduction (≥1 grade) was observed, placement of a PTMA implant was attempted. Implanted patients were evaluated with echocardiographic, quality of life, and exercise capacity metrics. Nineteen patients received a diagnostic PTMA study. Diagnostic PTMA was effective in 13 patients (MR grade 3.2±0.6 reduced to 2.0±1.0), and PTMA implants were placed in 9 patients. Four devices were removed uneventfully (7, 84, 197, and 216 days), 3 for annuloplasty surgery due to observed PTMA device migration and/or diminished efficacy. No procedure or device-related major adverse events with permanent sequela were observed in any of the diagnostic or implant patients. Sustained reductions of mitral annulus septal-lateral dimension from 3D echo reconstruction dimensions were observed (4.0±1.2 mm at 3 months).

Conclusions— Percutaneous implantation of the PTMA device is feasible and safe. Acute results demonstrate a possibly meaningful reduction of MR in responding patients. Sustained favorable geometric modification of the mitral annulus has been observed, though reduction of MR has been limited. The PTMA method warrants continued evaluation and development.

  A Jacobsen , J Wen , D. S Marks and A. Krogh

MicroRNAs (miRNAs) and small interfering RNAs (siRNAs), bound to Argonaute proteins (RISC), destabilize mRNAs through base-pairing with the mRNA. However, the gene expression changes after perturbations of these small RNAs are only partially explained by predicted miRNA/siRNA targeting. Targeting may be modulated by other mRNA sequence elements such as binding sites for the hundreds of RNA binding proteins (RNA-BPs) expressed in any cell, and this aspect has not been systematically explored. Across a panel of published experiments, we systematically investigated to what extent sequence motifs in 3' untranslated regions (UTRs) correlate with expression changes following transfection of small RNAs. The most significantly overrepresented motifs in down-regulated mRNAs are two novel U-rich motifs (URMs), UUUUAAA and UUUGUUU, recently discovered as binding sites for the ELAVL4 (also known as HuD) RNA-BP. Surprisingly, the most significantly overrepresented motif in up-regulated mRNAs is the heptanucleotide AU-rich element (ARE), UAUUUAU, which is known to affect mRNA stability via at least 20 different RNA-BPs. We show that destabilization mediated by the transfected miRNA is generally attenuated by ARE motifs and augmented by URM motifs. These ARE and URM signatures were confirmed in different types of published experiments covering eight different cell lines. Finally, we show that both ARE and URM motifs couple to presumed endogenous miRNA binding sites in mRNAs bound by Argonaute proteins. This is the first systematic investigation of 3' UTR motifs that globally couple to regulation by miRNAs and may potentially antagonize or cooperate with miRNA/siRNA regulation. Our results suggest that binding sites of miRNAs and RNA-BPs should be considered in combination when interpreting and predicting miRNA regulation in vivo.

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