Survival of Swiss-Webster mouse cerebellar granule neurons is promoted by a combination of potassium channel blockers

Cultured cerebellar granule neurons (CGN) are commonly used to assess neurotoxicity, but are routinely maintained in supraphysiological (25 mM) extracellular K⁺ concentrations [K⁺]_o. We investigated the effect of potassium channel blockade on survival of CGN derived from Swiss-Webster mice in supraphysiological (25 mM) and physiological (5.6 mM) [K⁺]_o. CGN were cultured for 5 days in 25 mM K⁺, then in 5.6 mM K⁺ or 25 mM K⁺ (control). Viability, assayed 24 h later by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) reduction and by lactate dehydrogenase (LDH) release, was ∼50% in 5.6 mM K⁺ versus 25 mM K⁺ (p < .001). Potassium channel blockers, 2 mM 4-aminopyridine (4-AP), 2 mM tetraethylammonium (TEA) or 1 mM Ba²⁺, individually afforded limited protection in 5.6 mM K⁺. However, survival in 5.6 mM K⁺ with a combination of 4-AP, TEA and Ba²⁺ was similar to survival in 25 mM K⁺ without blockers (p < .001 versus 5.6 mM K⁺ alone). CGN survival in 25 mM K⁺ was attenuated 25% by 2 μM nifedipine (p > .001), but nifedipine did not attenuate neuroprotection by K⁺ channel blockers. Together, these results suggest that the survival of CGN depends on the K⁺ permeability of the membrane rather than the activity of a particular type of K⁺ channel, and that the mechanism of neuroprotection by K⁺ channel blockers is different from that of elevated [K⁺]_o.

Prevalence of Mycobacterium avium subspecies paratuberculosis in Swiss raw milk cheeses collected at the retail level.

A total of 143 raw milk cheese samples (soft cheese, n = 9; semihard cheese, n = 133; hard cheese, n = 1), collected at the retail level throughout Switzerland, were tested for Mycobacterium avium ssp. paratuberculosis (MAP) by immunomagnetic capture plus culture on 7H10-PANTA medium and in supplemented BAC-TEC 12B medium, as well as by an F57-based real-time PCR system. Furthermore, pH and water activity values were determined for each sample. Although no viable MAP cells could be cultured, 4.2% of the raw milk cheese samples tested positive with the F57-based real-time PCR system, providing evidence for the presence of MAP in the raw material. As long as the link between MAP and Crohn’s disease in humans remains unclear, measures designed to minimize public exposure should also include a focus on milk products.

"Variations on Psycho Killer" - Musical Score. Commissioned by Pauline Kim Harris. A virtuosic set of variations on the famous Talking Heads song for solo violin. General information State: Unpublished Organisations: School of Creative Arts, Sonic Arts, UOA35 - Music, Drama, Dance and Performing Arts Authors: Lyon, E. Keywords: (Talking Heads, Violin Music) Publication date: 2012

Musical Score. Commissioned by Pauline Kim Harris. A virtuosic set of variations on the famous Talking Heads song for solo violin.

Premiere of "Spaced Images with Noise and Lines" Performance at the Joinery, Dublin, at at Spatial Music Collective concert. Authors: Lyon, E. Keywords: (Spatial Audio, Electroacoustic Music, Computer Music, Algorithmic Music) Publication date: 07 Oct 2011

Performance at the Joinery, Dublin, at at Spatial Music Collective concert

Three Melodies for Solo Vibraphone Recital performed by Cory Bracken, Percussionist Brooklyn College Studio 312 in Roosevelt Hall, Bedford Ave. Brooklyn, NY Authors: Lyon, E. Publication date: 27 Oct 2011

Thursday, October 27 · 7:00pm - 8:00pm
Location
Brooklyn College
Studio 312 in Roosevelt Hall, Bedford Ave.
Brooklyn, NY
Created By
Cory Bracken

"Noise Triptych" Performed by Ensemble String Noise at PIANOS, NYC. Authors: Lyon, E. Publication date: 20 Nov 2012

Performed by Ensemble String Noise at PIANOS, NYC.

"The End" for piano and computer. Performed by Shiau-uen Ding. Composer's Voice Concert Series: 15 Minutes of Fame. Jan Hus Church, NYC. General information State: Published Organisations: School of Creative Arts, Sonic Arts, UOA35 - Music, Drama, Dance and Performing Arts Authors: Lyon, E.

Performed by Shiau-uen Ding. Composer's Voice Concert Series: 15 Minutes of Fame. Jan Hus Church, NYC.

"The End." A winner of the 2012 "15 Minutes of Fame" competition. Authors: Lyon, E. Publication date: 2012

A winner of the 2012 "15 Minutes of Fame" competition.

Energy efficiency investments in the home: Swiss homeowners and expectations about future energy prices

Using conjoint choice experiments, we surveyed 473 Swiss homeowners about their preferences for energy efficiency home renovations.We find that homeowners are responsive to the upfront costs of the renovation projects, governmentoffered rebates, savings in energy expenses, time horizon over which such savings would be realized, and thermal comfort improvement. The implicit discount rate is low, ranging from 1.5 to 3%, depending on model specification. This is consistent with Hassett and Metcalf (1993) and Metcalf and Rosenthal (1995), and with the fact that our scenarios contain no uncertainty. Respondents who feel completely uncertain about future energy prices are more likely to select the status quo (no renovations) in any given choice task and weight the costs of the investments more heavily than the financial gains (subsidies and savings on the energy bills). Renovations are more likely when respondents believe that climate change considerations are important determinants of home renovations. Copyright © 2013 by the IAEE. All rights reserved.

Tunable 3D Plasmonic Swiss Rolls

Novel 3D plasmonic rolls are fabricated through strain-induced self-rolling of metallic nanopore sheets attached to elastomeric thin films, with optical properties tunable by varying the size and thickness of nanopores, and dynamically by light irradiation.

Five authors reply

We read with interest the comments offered by Drs. Hughes and Bradley (1) on our systematic review (2). Four single nucleotide polymorphisms (SNPs), rs9332739 and rs547154 in the complement component 2 gene (C2) and rs4151667 and rs641153 in the complement factor B gene (CFB), were pooled. Hughes and Bradley point out that we omitted the most common variant, rs12614. In fact, rs12614 is in high linkage disequilibrium (LD) with rs641153, which was included, and the major allele of both of these SNPs is in the range of 90% (population code, CEU, in the International HapMap Project (http://hapmap.ncbi.nlm.nih.gov/)). Moreover, our review was initiated in September 2010, at which point only 4 studies had published associations with rs12614, whereas 14 studies (n = 11,378) were available for rs641153. While it is true that both SNPs are better analyzed as a haplotype, these data were simply not available for pooling.
Hughes and Bradley also point out that we obtained and pooled new data that were not previously published. While it is recommended that contact with authors be completed as part of a comprehensive meta-analysis, we acknowledge that these additional data were not previously published and peer reviewed and, hence, do not have the same level of transparency. However, given that sample collections often increase over time and that the instrumentation for genotyping is continually improving, we thought that it would be advantageous to use the most recent information; this is a subjective decision.
We also agree that the allele frequencies given by Kaur et al. (3) were exactly opposite to those expected and were suggestive of strand flipping. However, we specifically queried this with the lead author on 2 separate occasions and were assured it was not.
Hughes and Bradley do make an interesting suggestion that SNPs in high LD should be used as a gauge of genotyping quality in HuGE reviews. This is an interesting idea but difficult to put into practice as the r2 parameter they propose as a measure of LD has some unusual properties. Although r2 is a measure of LD, it is also linked to the allele frequency; even small differences in allele frequencies between 2 linked SNPs can reduce the r2 dramatically. Wray (4) explored these effects and found that, at a baseline allele frequency of 10%, even a difference in allele frequency between 2 SNPs as small as 2% can drop the r2 value below 0.8. This degree of allele frequency difference is consistent with what could be expected for sampling error. Furthermore, when we look at 2 linked dialleleic SNPs, giving 4 possible haplotypes, the absence of 1 haplotype dramatically reduces r2, despite the 2 loci being in high LD as measured by D'. In fact, this is the situation for rs12614 and rs641153, where the low frequency of 1 haplotype means that the r2 is 0.01 but the D' is 1.
Hughes and Bradley also suggest consideration of genotype call rate restrictions as an inclusion criterion for metaanalysis. This would be more appropriate when focusing on genetic variants per se, as considered within the context of a genome-wide association study or other specific genetic analysis where large numbers of SNPs are evaluated (5).
The concerns raised by Hughes and Bradley reflect the limited ability of a meta-analysis based on summary data to tease out inconsistencies best identified at the individual level. We agree that SNPs in LD should be evaluated, but this will not necessarily be straightforward. A move to make genetic data sets publicly available, as in the Database of Genotypes and Phenotypes (http://www.ncbi.nlm.nih.gov/ gap), is a step in the right direction for greater transparency.