The effect of the apolipoprotein E phenotype on plasma lipids is not influenced by environmental variability: results of a Dutch twin study

We tested the influence of the apolipoprotein E (apoE) polymorphism on the intrapair differences in the levels of plasma cholesterol, plasma triglycerides, low density lipoprotein-cholesterol, apoB and apoE in monozygotic (MZ) twins, and estimated whether or not there was a interaction between the apoE polymorphism and environmental factors. In 65 MZ twin pairs, the intrapair differences in the measured lipoprotein parameters were similar in the different apoE phenotype classes. This indicates that the effect of the apoE polymorphism is not influenced by environmental variability between the MZ pair members and accordingly identifies the APOE gene as a "level" gene. © 1993 Springer-Verlag

Translational and Regulatory Challenges for Exon Skipping Therapies

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and interpretation of appropriate clinical outcome measures. Others are inherent to the antisense oligonucleotide (AON)-mediated exon skipping approach, which employs small modified DNA or RNA molecules to manipulate the splicing process. This is a new approach and only limited information is available on long-term safety and toxicity for most AON chemistries. Furthermore, AONs often act in a mutation-specific manner, in which case multiple AONs have to be developed for a single disease. A workshop focusing on preclinical development, trial design, outcome measures, and different forms of marketing authorization was organized by the regulatory models and biochemical outcome measures working groups of Cooperation of Science and Technology Action: "Networking towards clinical application of antisense-mediated exon skipping for rare diseases." The workshop included participants from patient organizations, academia, and members of staff from the European Medicine Agency and Medicine Evaluation Board (the Netherlands). This statement article contains the key outcomes of this meeting.status: publishe

Combined ecological risks of nitrogen and phosphorus in European freshwaters

Eutrophication is a key water quality issue triggered by increasing nitrogen (N) and phosphorus (P) levels and potentially posing risks to freshwater biota. We predicted the probability that an invertebrate species within a community assemblage becomes absent due to nutrient stress as the ecological risk (ER) for European lakes and streams subjected to N and P pollution from 1985 to 2011. The ER was calculated as a function of species-specific tolerances to NO3 - and total P concentrations and water quality monitoring data. Lake and stream ER averaged 50% in the last monitored year (i.e. 2011) and we observed a decrease by 22% and 38% in lake and stream ER (respectively) of river basins since 1985. Additionally, the ER from N stress surpassed that of P in both freshwater systems. The ER can be applied to identify river basins most subjected to eutrophication risks and the main drivers of impacts