The Arabidopsis RNA-binding protein FCA requires a lysine-specific demethylase 1 homolog to downregulate FLC.

A repressor of the transition to flowering in Arabidopsis is the MADS box protein FLOWERING LOCUS C (FLC). FCA, an RNA-binding protein, and FY, a homolog of the yeast RNA 3' processing factor Pfs2p, downregulate FLC expression and therefore promote flowering. FCA/FY physically interact and alter polyadenylation/3' processing to negatively autoregulate FCA. Here, we show that FCA requires FLOWERING LOCUS D (FLD), a homolog of the human lysine-specific demethylase 1 (LSD1) for FLC downregulation. FCA also partially depends on DICER-LIKE 3, involved in chromatin silencing. fca mutations increased levels of unspliced sense FLC transcript, altered processing of antisense FLC transcripts, and increased H3K4 dimethylation in the central region of FLC. These data support a close association of FCA and FLD in mediating H3K4 demethylation and thus transcriptional silencing of FLC and reveal roles for antisense RNA processing and DCL3 function in this regulation.

Chronology of the Grotte du Renne (France) and implications for the context of ornaments and human remains within the Châtelperronian

There is extensive debate concerning the cognitive and behavioral adaptation of Neanderthals, especially in the period when the earliest anatomically modern humans dispersed into Western Europe, around 35,000–40,000 B.P. The site of the Grotte du Renne (at Arcy-sur-Cure) is of great importance because it provides the most persuasive evidence for behavioral complexity among Neanderthals. A range of ornaments and tools usually associated with modern human industries, such as the Aurignacian, were excavated from three of the Châtelperronian levels at the site, along with Neanderthal fossil remains (mainly teeth). This extremely rare occurrence has been taken to suggest that Neanderthals were the creators of these items. Whether Neanderthals independently achieved this level of behavioral complexity and whether this was culturally transmitted or mimicked via incoming modern humans has been contentious. At the heart of this discussion lies an assumption regarding the integrity of the excavated remains. One means of testing this is by radiocarbon dating; however, until recently, our ability to generate both accurate and precise results for this period has been compromised. A series of 31 accelerator mass spectrometry ultra?ltered dates on bones, antlers, artifacts, and teeth from six key archaeological levels shows an unexpected degree of variation. This suggests that some mixing of material may have occurred, which implies a more complex depositional history at the site and makes it dif?cult to be con?dent about the association of artifacts with human remains in the Châtelperronian levels.

A potential vulnerability locus for schizophrenia on chromosome 6p24-22:evidence for genetic heterogeneity

In 265 Irish pedigrees, with linkage analysis we find evidence for a vulnerability locus for schizophrenia in region 6p24-22. The greatest lod score, assuming locus heterogeneity, is 3.51 (P = 0.0002) with D6S296. Another test, the C test, also supported linkage, the strongest results being obtained with D6S296 (P = 0.00001), D6S274 (P = 0.004) and D6S285 (P = 0.006). Non-parametric analysis yielded suggestive, but substantially weaker, findings. This locus appears to influence the vulnerability to schizophrenia in roughly 15 to 30% of our pedigrees. Evidence for linkage was maximal using an intermediate phenotypic definition and declined when this definition was narrowed or was broadened to include other psychiatric disorders.

Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families

This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues.

Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families

In our genome scan for schizophrenia genes in 265 Irish pedigrees, marker D5S818 in 5q22 produced the second best result of the first 223 markers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizophrenia in region 5q22-31. This region appears to be distinct from those chromosome 5 regions studied in two prior reports, but the same as that producing positive results in the report by Wildenauer and colleagues found elsewhere in this issue. The largest pairwise heterogeneity LOD (H-LOD) score was found with marker D5S393 (max 3.04, P = 0.0005), assuming a narrow phenotypic category, and a genetic model with intermediate heterozygotic liability. In marked contrast to the H-LOD scores from our sample with markers from the regions of interest on chromosomes 6p and 8p, expanding the disease definition to include schizophrenia spectrum or nonspectrum disorders produced substantially smaller scores, with a number of markers failing to yield positive values at any recombination fraction. Using multipoint H-LODS, the strongest evidence for linkage occurs under the narrow phenotypic definition and recessive genetic model, with a peak at marker D5S804 (max 3.35, P = 0.0002). Multipoint nonparametric linkage analysis produced a peak in the same location (max z = 2.84, P = 0.002) with the narrow phenotypic definition. This putative vulnerability locus appears to be segregating in 10-25% of the families studied, but this estimate is tentative. Comparison of individual family multipoint H-LOD scores at the regions of interest on chromosomes 6p, 8p and 5q showed that only a minority of families yield high lod scores in two or three regions.

A schizophrenia locus may be located in region 10p15-p11

In our genomic scan of 265 Irish families with schizophrenia, we have thus far generated modest evidence for the presence of vulnerability genes in three chromosomal regions, i.e., 5q21-q31, 6p24-p22, and 8p22-p21. Outside of those regions, of all markers tested to date, D10S674 produced one of the highest pairwise heterogeneity lod (H-LOD) scores, 3.2 (P = 0.0004), when initially tested on a subset of 88 families. We then tested a total of 12 markers across a region of 32 centimorgans in region 10p15-p11 of all 265 families. The strongest evidence for linkage occurred assuming an intermediate phenotypic definition, and a recessive genetic model. The largest pairwise H-LOD score was found with marker D10S2443 (maximum 1.95, P = 0.005). Using multipoint H-LODs, we found a broad peak (maximum 1.91, P = 0.006) extending over the 11 centimorgans from marker D10S674 to marker D10S1426. Multipoint nonparametric linkage analysis produced a much broader peak, but with the maximum in the same location near D10S2443 (maximum z = 1.88, P = 0.03). Based on estimates from the multipoint analysis, this putative vulnerability locus appears to be segregating in 5-15% of the families studied, but this estimate should be viewed with caution. When evaluated in the context of our genome scan results, the evidence suggests the possibility of a fourth vulnerability locus for schizophrenia in these Irish families, in region 10p15-p11.

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

Le thème du mensonge dans Le Petit Canard de Jacques Laurent’

ADEFFI annual conference
Trinity College Dublin
October 2007

La présence ambiguë du "bon Allemand" dans le roman français de l’immédiat après-Seconde Guerre mondiale: Gary, Bory, Curtis

French Seminar Series
Belfast, December 2010

Scalable black-box prediction models for multi-dimensional adaptation on NUMA multi-cores

This paper presents a scalable, statistical ‘black-box’ model for predicting the performance of parallel programs on multi-core non-uniform memory access (NUMA) systems. We derive a model with low overhead, by reducing data collection and model training time. The model can accurately predict the behaviour of parallel applications in response to changes in their concurrency, thread layout on NUMA nodes, and core voltage and frequency. We present a framework that applies the model to achieve significant energy and energy-delay-square (ED2) savings (9% and 25%, respectively) along with performance improvement (10% mean) on an actual 16-core NUMA system running realistic application workloads. Our prediction model proves substantially more accurate than previous efforts.