Synthesis of the PPARbeta/delta-selective agonist GW501516 and C4-thiazole-substituted analogs

Sequential, position-selective, Pd-catalyzed cross-coupling reactions of 2,4-dibromo-5-hydroxymethylthiazole provided the scaffold for the synthesis of GW501516, the most potent PPARbeta/delta agonist yet described, and equally selective analogs at the thiazole-C4 position.     

Regulator of calcineurin 1 (RCAN1) facilitates neuronal apoptosis through caspase-3 activation

Individuals with Down syndrome (DS) will inevitably develop Alzheimer disease (AD) neuropathology sometime after middle age, which may be attributable to genes triplicated in individuals with DS. The characteristics of AD neuropathology include neuritic plaques, neurofibrillary tangles, and neuronal loss in various brain regions. The mechanism underlying neurodegeneration in AD and DS remains elusive. Regulator of calcineurin 1 (RCAN1) has been implicated in the pathogenesis of DS. Our data show that RCAN1 expression is elevated in the cortex of DS and AD patients. RCAN1 expression can be activated by the stress hormone dexamethasone. A functional glucocorticoid response element was identified in the RCAN1 isoform 1 (RCAN1-1) promoter region, which is able to mediate the up-regulation of RCAN1 expression. Here we show that overexpression of RCAN1-1 in primary neurons activates caspase-9 and caspase-3 and subsequently induces neuronal apoptosis. Furthermore, we found that the neurotoxicity of RCAN1-1 is inhibited by knock-out of caspase-3 in caspase-3(-/-) neurons. Our study provides a novel mechanism by which RCAN1 functions as a mediator of stress- and Aβ-induced neuronal death, and overexpression of RCAN1 due to an extra copy of the RCAN1 gene on chromosome 21 contributes to AD pathogenesis in DS.     

Specific primers for the detection of the black-yeast fungus associated with lethargic crab disease (LCD)

Lethargic crab disease (LCD) is an emerging infirmity that has been causing extensive mortalities in populations of the mangrove land crab Ucides cordatus (Ocypodidae) along the Atlantic coast of Brazil. Previous studies have indicated that LCD is associated with a dematiaceous fungus, Exophiala cancerae de Hoog et al. In the present study, we sequenced the internal transcribed spacer (ITS) of the rDNA region of this black yeast species and developed species-specific PCR primers. Sensitivity tests indicated that the developed protocol is capable of detecting very small amounts of target DNA. Also, the application of the protocol to a variety of other dematiaceous fungi did not generate any false positives. The specific primers provided in the present study represent an important tool for rapidly surveying a large number of crab individuals, as well as environmental samples. Such knowledge will be instrumental in understanding the epidemiological dynamics of LCD.     

cn.FARMS: a latent variable model to detect copy number variations in microarray data with a low false discovery rate

Cost-effective oligonucleotide genotyping arrays like the Affymetrix SNP 6.0 are still the predominant technique to measure DNA copy number variations (CNVs). However, CNV detection methods for microarrays overestimate both the number and the size of CNV regions and, consequently, suffer from a high false discovery rate (FDR). A high FDR means that many CNVs are wrongly detected and therefore not associated with a disease in a clinical study, though correction for multiple testing takes them into account and thereby decreases the study's discovery power. For controlling the FDR, we propose a probabilistic latent variable model, 'cn.FARMS', which is optimized by a Bayesian maximum a posteriori approach. cn.FARMS controls the FDR through the information gain of the posterior over the prior. The prior represents the null hypothesis of copy number 2 for all samples from which the posterior can only deviate by strong and consistent signals in the data. On HapMap data, cn.FARMS clearly outperformed the two most prevalent methods with respect to sensitivity and FDR. The software cn.FARMS is publicly available as a R package at http://www.bioinf.jku.at/software/cnfarms/cnfarms.html.     

Testing a molecular protocol to monitor the presence of golden mussel larvae (Limnoperna fortunei) in plankton samples

The golden mussel (Limnoperna fortunei, Mollusca: Mytilidae)is an emerging invasive species in freshwater environments inSouth America, causing extensive environmental and economicimpacts. A molecular method to detect larvae of the golden musselin plankton samples has been recently developed and holds promisefor becoming an important way to monitor the expansion of goldenmussel populations. In the present study, we conduct, for thefirst time, field tests of this method by comparing its performancewith alternative sampling efforts (microscopy and manual searchfor adults). In addition, we test different modifications ofthe molecular method to deal with PCR inhibition in environmentalsamples. The results indicate that the molecular method is veryefficient, being faster and more sensitive that microscopy methods.Therefore, the molecular method tested in the present studycan represent an invaluable tool in large-scale monitoring effortsof the golden mussel throughout its introduced range.     

Vertical Stratification and Caloric Content of the Standing Fruit Crop in a Tropical Lowland Forest1

Fruit abundance in tropical forests thus far has been studied in relation to consumer populations. Area–based surveys that focus on the quantity and quality of the standing fruit crop of an entire plant community, however, are lacking. This paper presents the results of a four–month study on the seasonality and vertical distribution of the standing fruit crop within a tropical forest during the dry season in southern Venezuela. Fruit numbers ranged from 262,000 to 424,000 fruits/ha. The standing crop was between 39 and 92 kg/ha, yielding 67,000 to 126,000 kj. Fruits were not evenly distributed in different forest layers. They were most abundant in the canopy above 16 m and scarce between 4 and 12 m above the ground. Despite a scarcity of fruits in the mid–strata, the caloric value of the total fruit supply peaked within a narrow layer of subcanopy at 12 to 16 m above ground due to a high amount of energy per fruit. Palms fruited mostly in this layer, their fruits contributing 59 percent of the energy supplied by all fruits. Above 12 m, we found a broader range of fruit sizes than in the forest below 12m. Small–sized fruits were distributed in the understory and in the canopy but were nearly absent from die mid–story. Corresponding to the abundance of small–sized fruits in the canopy, small frugivorous species, such as members of the Thraupidae, limited their foraging to the canopy strata whereas larger avian frugivores foraged mainly in die mid–story.