Combining expert‐adjusted forecasts

It is well known that a combination of model‐based forecasts can improve upon each of the individual constituent forecasts. Most forecasts available in practice are, however, not purely based on econometric models but entail adjustments, where experts with domain‐specific knowledge modify the original model forecasts. There is much evidence that expert‐adjusted forecasts do not necessarily improve the pure model‐based forecasts. In this paper we show, however, that combined expert‐adjusted model forecasts can improve on combined model forecasts, in the case when the individual expert‐adjusted forecasts are not better than their associated model‐based forecasts. We discuss various implications of this finding.     

Integrative taxonomy of the gymnophthalmid lizard Neusticurus rudis Boulenger, 1900 identifies a new species in the eastern Pantepui region,north-eastern South America

ABSTRACT

The gymnophthalmid lizard genus Neusticurus Duméril and Bibron, 1839 currently contains six described species. One of them, Neusticurus rudis Boulenger, 1900 has a long history of taxonomic confusion, and uncertainty remains about the number of species involved under that name, especially in the Pantepui region. Our molecular phylogenetic (concatenation and species tree) and morphological (morphometrics, external and hemipenial morphology) analyses confirm Neusticurus rudis as a species complex with several candidate species in the eastern Pantepui region. Neusticurus rudis is here redescribed based on the re-examination of the holotype and 10 specimens from the vicinity of the type locality (ca. 15 km airline) in Guyana. The geographic distribution of N. rudis sensu stricto is restricted to east of the Venezuelan Gran Sabana, extending from the slopes of Mount Roraima in Venezuela through the slopes of Maringma-tepui and Wayalayeng to Mount Ayanganna in Guyana, between 678 and 1500 m elevation. Populations tentatively assigned to N. rudis also occur from Mount Wokomung in the Pakaraima Mountains of Guyana to the Iwokrama Forest Reserve in Guyana, between 159 and 1234 m elevation. A new Neusticurus species is described from the uplands and highlands of the eastern Pantepui region, west of the Venezuelan Gran Sabana in Brazil and Venezuela, between 900 and 2200 m elevation. Populations provisionally assigned to the new species were also found from the La Escalera region to Chivatón, the summit of Abakapá-tepui and the slopes and summit of Auyán-tepui, Venezuela, between 1100 and 2203 m elevation. Our results suggest the Gran Sabana as a possible recent biogeographical barrier for the genus in the region and indicate that tepui-summit Neusticurus populations derive from uplands populations that shifted their habitat preference.

www.zoobank.org/lsid:zoobank.org:pub:33DCF862-11CF-4FD0-B4D6-706E2C6A339E     

Molecular structure of a left-handed double helical DNA fragment at atomic resolution

The DNA fragment d(CpGpCpGpCpG) crystallises as a left-handed double helical molecule with Watson-Crick base pairs and an antiparallel organisation of the sugar phosphate chains. The helix has two nucleotides in the asymmetric unit and contains twelve base pairs per turn. It differs significantly from right-handed B-DNA.     

Bacterial pore-forming toxins: The (w)hole story?

Pore-forming toxins (PFTs) are the most common class of bacterial protein toxins and constitute important bacterial virulence factors. The mode of action of PFT is starting to be better understood. In contrast, little is known about the cellular response to this threat. Recent studies reveal that cells do not just swell and lyse, but are able to sense and react to pore formation, mount a defense, even repair the damaged membrane and thus survive. These responses involve a variety of signal-transduction pathways and sophisticated cellular mechanisms such as the pathway regulating lipid metabolism. In this review we discuss the different classes of bacterial PFTs and their modes of action, and provide examples of how the different bacteria use PFTs. Finally, we address the more recent field dealing with the eukaryotic cell response to PFT-induced damage. Received 19 September 2007; received after revision 18 October 2007; accepted 23 October 2007     

Endocannabinoids and β-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels

We investigated the involvement of endocannabinoids in the control of neuronal damage and memory retention loss in rodents treated with the β-amyloid peptide (1–42) (BAP). Twelve days after stereotaxic injection of BAP into the rat cortex, and concomitant with the appearance in the hippocampus of markers of neuronal damage, 2-arachidonoyl glycerol, but not anandamide, levels were enhanced in the hippocampus. VDM-11 (5 mg/kg, i.p.), an inhibitor of endocannabinoid cellular reuptake, significantly enhanced rat hippocampal and mouse brain endocannabinoid levels when administered sub-chronically starting either 3 or 7 days after BAP injection and until the 12–14th day. VDM-11 concomitantly reversed hippocampal damage in rats, and loss of memory retention in the passive avoidance test in mice, but only when administered from the 3rd day after BAP injection. We suggest that early, as opposed to late, pharmacological enhancement of brain endocannabinoid levels might protect against β-amyloid neurotoxicity and its consequences. Received 26 January 2006; received after revision 24 March 2006; accepted 12 April 2006     

Mutations in different components of FGF signaling in LADD syndrome

Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by lacrimal duct aplasia, malformed ears and deafness, small teeth and digital anomalies. We identified heterozygous mutations in the tyrosine kinase domains of the genes encoding fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3) in LADD families, and in one further LADD family, we detected a mutation in the gene encoding fibroblast growth factor 10 (FGF10), a known FGFR ligand. These findings increase the spectrum of anomalies associated with abnormal FGF signaling.     

Germline KRAS mutations cause Noonan syndrome

Noonan syndrome (MIM 163950) is characterized by short stature, facial dysmorphism and cardiac defects. Heterozygous mutations in PTPN11, which encodes SHP-2, cause approximately 50% of cases of Noonan syndrome. The SHP-2 phosphatase relays signals from activated receptor complexes to downstream effectors, including Ras. We discovered de novo germline KRAS mutations that introduce V14I, T58I or D153V amino acid substitutions in five individuals with Noonan syndrome and a P34R alteration in a individual with cardio-facio-cutaneous syndrome (MIM 115150), which has overlapping features with Noonan syndrome. Recombinant V14I and T58I K-Ras proteins show defective intrinsic GTP hydrolysis and impaired responsiveness to GTPase activating proteins, render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage-specific manner. These studies establish germline KRAS mutations as a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is, in large part, due to hyperactive Ras.     

Chronic quercetin exposure affects fatty acid catabolism in rat lung

Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. Previously, we identified rat lung as a quercetin target tissue. To assess relevant in vivo health effects of quercetin, we analyzed mechanisms of effect in rat lungs of a chronic (41 weeks) 1% quercetin diet using whole genome microarrays. We show here that fatty acid catabolism pathways, like beta-oxidation and ketogenesis, are up-regulated by the long-term quercetin intervention. Up-regulation of genes (Hmgcs2, Ech1, Acox1, Pcca, Lpl and Acaa2) was verified and confirmed by quantitative real time PCR. In addition, free fatty acid levels were decreased in rats fed the quercetin diet, confirming that quercetin affects fatty acid catabolism. This in vivo study demonstrates for the first time that fatty acid catabolism is a relevant process that is affected in rats by chronic dietary quercetin. Received 6 July 2006; received after revision 29 August 2006; accepted 28 September 2006