Coenzyme Q10 (CoQ10) deficiency has been associated with various clinical phenotypes, including an infantile multisystem disorder. The authors report a 33-month-old boy who presented with corticosteroid-resistant nephrotic syndrome in whom progressive encephalomyopathy later developed. CoQ10 was decreased both in muscle and in fibroblasts. Oral CoQ10 improved the neurologic picture but not the renal dysfunction.

Spironolactone improves LV volumes and function; furthermore, it improves exercise tolerance at the highest administered dose. Our data might explain the mortality reduction during aldosterone antagonism in patients with HF.

Skeletal muscle mass is an independent predictor of peak Vo2 and VE/VCo2 slope in stable noncachectic patients with CHF. Future studies will determine whether an increase in skeletal muscle mass in the individual patient might result in an improvement in parameters of exercise capacity.

The transport of nucleic acids through membrane pores is a fundamental biological process that occurs in all living organisms. It occurs, for example, during the import of viral DNA into the host cell or during the nuclear pore complex-mediated transport of mRNA in and out the cell nucleus and has implications in nucleic acid drug delivery and gene therapy. Here we describe an engineered DNA transporter that is able to recognize and chaperone a specific DNA molecule across a biological membrane under a fixed transmembrane potential. The transported DNA strand is then released by a simple mechanism based on DNA strand displacement. This nanopore machine might be used to separate or concentrate nucleic acids or to transport genetic information across biological membranes.

Many important processes in biology involve the translocation of a biopolymer through a nanometer-scale pore. Moreover, the electrophoretic transport of DNA across nanoscale pores is under intense investigation for single-molecule DNA sequencing and analysis. Here we show that the precise patterning of the entry and the middle section of the ClyA nanopore with positive charges are crucial to observe the electrophoretic translocation of DNA at physiological ionic strength. Surprisingly, the strongly electronegative 3.3 nm internal constriction of the nanopore did not require modifications. Further, DNA translocation could only be observed from the wide entry of the nanopore. Our results suggest that the engineered positive charges are important to align the DNA in order to overcome the entropic and electrostatic barriers for DNA translocation through the narrow constriction. The dependencies of nucleic acid translocations on the Debye length of the solution are consistent with a physical model where the capture of double stranded DNA is diffusion-limited while the capture of single stranded DNA is reaction-limited. KeywordsClyA nanopore; DNA rotaxane; protein engineering; DNA sequencing; bacteriophage DNA sliding The translocation of DNA across specialized proteins is an important biological process. Bacteria use secretin channels in their pili to uptake or transfer DNA, while viruses such as phages use their portal proteins to either pack genomic DNA into the viral capsid or to eject it into target cells. In the three domains of life, β-clamp proteins form a toroid structure that encircles and slides along DNA to aid the function of DNA processing enzymes. Portal proteins in all known bacteriophages (λ, P22, T4, T3, T7, SPP1, P2 and ϕ29)1 and many components of secretin channels2 form dodecameric rings. The available crystal structures of portal proteins (ϕ29,3 SPP1,4 P225 and T46) have revealed the presence of a central channel through which dsDNA must both enter during packaging and exit during injection. While the interior channel lining is mostly negatively charged, a few positively charged amino acids, arranged as rings along the length of the pore, can also be found. A similar