Regulation of mother-to-offspring transmission of mtDNA heteroplasmy

mtDNA is present in multiple copies in each cell derived from the expansions of those in the oocyte. Heteroplasmy, more than one mtDNA variant, may be generated by mutagenesis, paternal mtDNA leakage, and novel medical technologies aiming to prevent inheritance of mtDNA-linked diseases. Heteroplasmy phenotypic impact remains poorly understood. Mouse studies led to contradictory models of random drift or haplotype selection for mother-to-offspring transmission of mtDNA heteroplasmy. Here, we show that mtDNA heteroplasmy affects embryo metabolism, cell fitness, and induced pluripotent stem cell (iPSC) generation. Thus, genetic and pharmacological interventions affecting oxidative phosphorylation (OXPHOS) modify competition among mtDNA haplotypes during oocyte development and/or at early embryonic stages. We show that heteroplasmy behavior can fall on a spectrum from random drift to strong selection, depending on mito-nuclear interactions and metabolic factors. Understanding heteroplasmy dynamics and its mechanisms provide novel knowledge of a fundamental biological process and enhance our ability to mitigate risks in clinical applications affecting mtDNA transmission

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce

Sensitivity enhancement of nanoplasmonic sensors on low refractive index substrates

Metal films perforated by nanoholes constitute a powerful platform for surface plasmon resonance biosensing. We find that the refractive index sensitivity of nanohole arrays increases if their resonance is red-shifted by increasing the separation distance between holes. However, an additional sensitivity enhancement occurs if the nanohole sensors are manufactured on low index substrates, despite the fact such substrates significantly blue-shift the resonance. We find a ∼40% higher bulk refractive index sensitivity for a system of -100 nm holes in 20 nm gold films fabricated on Teflon substrates (n=1.32) compared to the case when conventional glass substrates (n=1.52) are used. A similar improvement is observed for the case when a thin layer of dielectric material is deposited on the samples. These results can be understood by considering the electric field distribution induced by the so-called antisymmetric surface plasmon polariton in the thin gold films

Interferometric biosensors for environmental pollution detection

20 páginas.-- Narayanaswamy, Ramaier; Wolfbeis, Otto S. (Eds.)Peer reviewe