Why did the Swiss Young Socialist's initiative against speculation on agricultural foodstuff fail to be approved in Switzerland ?

Agricultural commodity prices have undergone exceptional volatility in the past decade. Staple foods such as rice, wheat and corn saw their prices rally to unprecedented levels especially in 2008 and 2011. During these periods, social unrest and food riots burst in several developing countries around the world sparking the debate on the role of commodities financialisation in the food price formation. Commodity speculators were once again put in the limelight and their activities fingered as the culprit behind food exorbitant prices. Firm believers that speculation was the root cause of commodities’ prices surge, the Swiss Young Socialist Party concluded that prohibiting speculation on agricultural foodstuff was the easiest way to curb staple food price rallies; hence, a surefire way to fight hunger in the world. This conclusion led to the inception of the popular initiative called “No speculation on agricultural foodstuff ” that was submitted to popular vote on February 28th 2016 in Switzerland. Despite its good intentions, the popular initiative was refused by 59,9% of the Swiss electorate. Acknowledging that Swiss voters were not indifferent to food prices surges and food riots around the world, this work digs into the reasons that led Switzerland to refuse the initiative. Speculative practices on commodities have always instigated controversies. The literature review associates as many advantages as harms to the practice of speculation. Having to decide on a misty subject not clearly explained or understood by politicians, the Swiss electorate based their decision on other facts than their knowledge about the impact of speculation on food prices. Results obtained from a local surveyashows that 58.2% of the Swiss electorate believed speculation was a bad thing and it contributed to foodstuff price rallies. However, the proportion of voters who supported the initiative was inferior to 50% of the total electorate. Based on this fact, we assume that a significant share of voters who believed speculation was a bad thing did not support the initiative. Furthermore, we conclude that perceiving speculation as a bad thing was not a sufficient reason to vote in favor of the initiative. The suspicion that prohibiting speculation in Switzerland concealed headwinds to the Swiss commodity-trading sector represented the greatest obstacle for the initiative. This study found evidences that the initiative against speculation bore the brunt of the importance of the commodity-trading sector for Switzerland. Considering that 65% of surveyed voters declared to be worried about the Swiss trading sector, we can suggest that the Swiss electorate was well aware of the position of hundreds of commoditytrading companies headquartered in Switzerland whom contribute with thousands of well-paid jobs and a significant share of the Swiss GDP. By juxtaposing voters’ opinions on speculation and their concerns about the initiative covert headwinds for the Swiss economy, we gathered noteworthy information concerning the Swiss electorate’s decision-making process. In sum, this work suggests that the Swiss electorate believes that a solution to fight hunger in the world is more complex than merely banning speculation on agricultural products. Moreover, Switzerland had too much at stake and the country could not afford to put one of its most lucrative economical sectors in jeopardy in order to engage in a battle that had very little chance to be won

Ancestral Origin of the ATTCT Repeat Expansion in Spinocerebellar Ataxia Type 10 (SCA10)

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1) a shared disease haplotype for all Brazilian and one of the Mexican families, and (2) closely-related haplotypes for the additional SCA10 Mexican families; (3) little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4) a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil

In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5′ splice sites

We have found that two previously reported exonic mutations in the PINK1 and PARK7 genes affect pre-mRNA splicing. To develop an algorithm to predict underestimated splicing consequences of exonic mutations at the 5′ splice site, we constructed and analyzed 31 minigenes carrying exonic splicing mutations and their derivatives. We also examined 189 249 U2-dependent 5′ splice sites of the entire human genome and found that a new variable, the SD-Score, which represents a common logarithm of the frequency of a specific 5′ splice site, efficiently predicts the splicing consequences of these minigenes. We also employed the information contents (Ri) to improve the prediction accuracy. We validated our algorithm by analyzing 32 additional minigenes as well as 179 previously reported splicing mutations. The SD-Score algorithm predicted aberrant splicings in 198 of 204 sites (sensitivity = 97.1%) and normal splicings in 36 of 38 sites (specificity = 94.7%). Simulation of all possible exonic mutations at positions −3, −2 and −1 of the 189 249 sites predicts that 37.8, 88.8 and 96.8% of these mutations would affect pre-mRNA splicing, respectively. We propose that the SD-Score algorithm is a practical tool to predict splicing consequences of mutations affecting the 5′ splice site

Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities

We developed a simple algorithm, i-Score (inhibitory-Score), to predict active siRNAs by applying a linear regression model to 2431 siRNAs. Our algorithm is exclusively comprised of nucleotide (nt) preferences at each position, and no other parameters are taken into account. Using a validation dataset comprised of 419 siRNAs, we found that the prediction accuracy of i-Score is as good as those of s-Biopredsi, ThermoComposition21 and DSIR, which employ a neural network model or more parameters in a linear regression model. Reynolds and Katoh also predict active siRNAs efficiently, but the numbers of siRNAs predicted to be active are less than one-eighth of that of i-Score. We additionally found that exclusion of thermostable siRNAs, whose whole stacking energy (ΔG) is less than −34.6 kcal/mol, improves the prediction accuracy in i-Score, s-Biopredsi, ThermoComposition21 and DSIR. We also developed a universal target vector, pSELL, with which we can assay an siRNA activity of any sequence in either the sense or antisense direction. We assayed 86 siRNAs in HEK293 cells using pSELL, and validated applicability of i-Score and the whole ΔG value in designing siRNAs

Human branch point consensus sequence is yUnAy

Yeast carries a strictly conserved branch point sequence (BPS) of UACUAAC, whereas the human BPS is degenerative and is less well characterized. The human consensus BPS has never been extensively explored in vitro to date. Here, we sequenced 367 clones of lariat RT-PCR products arising from 52 introns of 20 human housekeeping genes. Among the 367 clones, a misincorporated nucleotide at the branch point was observed in 181 clones, for which we can precisely pinpoint the branch point. The branch points were comprised of 92.3% A, 3.3% C, 1.7% G and 2.8% U. Our analysis revealed that the human consensus BPS is simply yUnAy, where the underlined is the branch point at position zero and the lowercase pyrimidines (‘y’) are not as well conserved as the uppercase U and A. We found that the branch points are located 21–34 nucleotides upstream of the 3′ end of an intron in 83% clones. We also found that the polypyrimidine tract spans 4–24 nucleotides downstream of the branch point. Our analysis demonstrates that the human BPSs are more degenerative than we have expected and that the human BPSs are likely to be recognized in combination with the polypyrimidine tract and/or the other splicing cis-elements

doi:10.1093/nar/gkn073 Human branch point consensus sequence is yUnAy

Yeast carries a strictly conserved branch point sequence (BPS) of UACUAAC, whereas the human BPS is degenerative and is less well characterized. The human consensus BPS has never been extensively explored in vitro to date. Here, we sequenced 367 clones of lariat RT-PCR products arising from 52 introns of 20 human housekeeping genes. Among the 367 clones, a misincorporated nucleotide at the branch point was observed in 181 clones, for which we can precisely pinpoint the branch point. The branch points were comprised of 92.3 % A, 3.3 % C, 1.7 % G and 2.8 % U. Our analysis revealed that the human consensus BPS is simply yUnAy, where the underlined is the branch point at position zero and the lowercase pyrimidines (‘y’) are not as well conserved as the uppercase U and A. We found that the branch points are located 21–34 nucleotides upstream of the 3 ’ end of an intron in 83 % clones. We also found that the polypyrimidine tract spans 4–24 nucleotides downstream of the branch point. Our analysis demonstrates that the human BPSs are more degenerative than we have expected and that the human BPSs are likely to be recognized in combination with the polypyrimidine tract and/or the other splicing cis-elements

The Unstable CCTG Repeat Responsible for Myotonic Dystrophy Type 2 Originates from an <em>Alu</em>Sx Element Insertion into an Early Primate Genome

<div><p>Myotonic dystrophy type 2 (DM2) is a subtype of the myotonic dystrophies, caused by expansion of a tetranucleotide CCTG repeat in intron 1 of the zinc finger protein 9 (<em>ZNF9</em>) gene. The expansions are extremely unstable and variable, ranging from 75–11,000 CCTG repeats. This unprecedented repeat size and somatic heterogeneity make molecular diagnosis of DM2 difficult, and yield variable clinical phenotypes. To better understand the mutational origin and instability of the <em>ZNF9</em> CCTG repeat, we analyzed the repeat configuration and flanking regions in 26 primate species. The 3′-end of an <em>Alu</em>Sx element, flanked by target site duplications (5′-ACTRCCAR-3′or 5′-ACTRCCARTTA-3′), followed the CCTG repeat, suggesting that the repeat was originally derived from the <em>Alu</em> element insertion. In addition, our results revealed lineage-specific repetitive motifs: pyrimidine (CT)-rich repeat motifs in New World monkeys, dinucleotide (TG) repeat motifs in Old World monkeys and gibbons, and dinucleotide (TG) and tetranucleotide (TCTG and/or CCTG) repeat motifs in great apes and humans. Moreover, these di- and tetra-nucleotide repeat motifs arose from the poly (A) tail of the <em>Alu</em>Sx element, and evolved into unstable CCTG repeats during primate evolution. <em>Alu</em> elements are known to be the source of microsatellite repeats responsible for two other repeat expansion disorders: Friedreich ataxia and spinocerebellar ataxia type 10. Taken together, these findings raise questions as to the mechanism(s) by which <em>Alu</em>-mediated repeats developed into the large, extremely unstable expansions common to these three disorders.</p> </div

Sequence configurations of the DM2 repeat in 24 primates species.

<p>Sequence configurations of the DM2 repeat in 24 primates species.</p