Synphilin suppresses α-synuclein neurotoxicity in a Parkinson's disease Drosophila model

Parkinson's disease (PD) is the second most common neurodegenerative disorder in humans. It affects 1% of the population over 65-years old. Its causes are environmental and genetic. As the world population ages, there is an urgent need for better and more detailed animal models for this kind of disease. In this work we show that the use of transgenic Drosophila is comparable to more complicated and costly animal models such as mice. The Drosophila model behaves very similar to the equivalent transgenic mice model. We show that both Synphilin-1 and α-synuclein are toxic by themselves, but when co-expressed, they suppress their toxicity reciprocally. Importantly, the symptoms induced in the fly can be treated and partially reverted using standard PD pharmacological treatments. This work showcases Drosophila as a detailed and multifaceted model for Parkinson's disease, providing a convenient platform in which to study and find new genetic modifiers of PD. genesis 49:392-402, 2011.     

The effects of winter severity and population density on body stores in the Iberian wild goat (<Emphasis Type="Italic">Capra pyrenaica</Emphasis>) in a highly seasonal mountain environment

We studied the factors that determined kidney fat stores (KFs) and kidney stores (Ks)—defined as the residuals from the linear regression of kidney mass and kidney fat, respectively, on body weight—in 463 Iberian wild goats (Capra pyrenaica) from the Sierra Nevada (southern Spain). Despite the fact that body stores in both sexes were highest during the warmest months of the year and lowest during the coldest months when food resources are limited, the observed pattern was sex- and age-dependent. The KFs of male goats fell more than those of females in winter, and the yearlings of both sexes needed one season more than young or adults to restore their KFs. Goats of all age classes showed the same seasonal patterns in their Ks, although Ks were lower in females than in males throughout the yearly cycle. In addition, we found strong delayed effects of both snowfalls and population density on body stores, and in years with a lot of snow, goats' KFs reached their lowest levels in the current winter–spring, but the highest in the following summers and autumns. This pattern was less noticeable in the Ks. Population density negatively affected the body stores of wild goats, especially in winter, and the amount of snow fallen in the year of birth (cohort effect) did not seem to influence the body stores in our data set. In addition, we assessed the accuracy of the residuals from the regression between body size and body mass for monitoring body condition of live wild goats and concluded that, although it poorly indicates fat stores, it could be used as a general proxy of body condition. Finally, we discuss the expected effects of climate warming on body stores in this Mediterranean Caprinae species.     

Trichoderma: the genomics of opportunistic success

Trichoderma is a genus of common filamentous fungi that display a remarkable range of lifestyles and interactions with other fungi, animals and plants. Because of their ability to antagonize plant-pathogenic fungi and to stimulate plant growth and defence responses, some Trichoderma strains are used for biological control of plant diseases. In this Review, we discuss recent advances in molecular ecology and genomics which indicate that the interactions of Trichoderma spp. with animals and plants may have evolved as a result of saprotrophy on fungal biomass (mycotrophy) and various forms of parasitism on other fungi (mycoparasitism), combined with broad environmental opportunism.     

A customized pigmentation SNP array identifies a novel SNP associated with melanoma predisposition in the SLC45A2 gene

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.     

Dissecting Genetic Structure in Farmer Selections of Theobroma Cacao in the Peruvian Amazon: Implications for on Farm Conservation and Rehabilitation

Knowledge of genetic diversity in farmers?? selections is essential for planning on-farm conservation and rehabilitation. Using 15 microsatellite loci, we analyzed parentage and population structure in 220 farmer selections of cacao from the Huallaga valley in Peruvian Amazon. A high level of allele richness and heterozygosity were detected in these selections. Coordination analysis showed that these farmer selections are mainly comprised of hybrids derived from Trinitario and Upper Amazon Forastero germplasm. Bayesian clustering analysis assigned 54 selections as Trinitario and 166 as Upper Amazon Forastero hybrids. Parentage analysis identified 15 international clones as probable parents for 96 farmer selections, which corresponded to a fraction of the known hybrid families disseminated in this region in the late 1980s. Combined analysis of demographic and molecular data revealed a significant spatial autocorrelation (r?=?0.235; P?=?0.006) at short geographical distances (<5.0 km). This patch-like distribution of spatial heterogeneity suggests a significant ??neighborhood effects?? in seeds distribution or variety adoption, where closely related hybrid progenies were adopted in the neighboring farms or villages. The outcomes of this study indicate that in spite of the introgressions of exotic germplasm in the past, Upper Amazon Forastero is still the dominant component in the Huallaga valley of Peru. The high level of on-farm diversity can offer needed variability for participatory selection of superior clones in this low input, small-scale production system, where adaptability to specific environment is more preferred than in a high input, large scale production system.     

Leaf-litter processing in headwater streams of northern Iberian Peninsula: moderate levels of eutrophication do not explain breakdown rates

Agricultural and urban runoffs result in increased nitrogen and phosphorus inputs in rivers and are the cause of eutrophication. Headwater streams are less frequently affected by these impairments because of the low-to-moderate human activities there. Eutrophication can affect the structure and function of benthic communities in headwater streams, stimulating the activity of heterotrophic microorganisms and macroinvertebrates on a pivotal process such as leaf-litter decomposition. In this study, we monitored the breakdown of alder leaves in six headwater streams that constitute a moderate nutrient enrichment gradient. Breakdown experiments were conducted in autumn–winter and leaf carbon, nitrogen and phosphorus, and associated aquatic hyphomycetes and macroinvertebrates were determined. The increase in nutrient availability in the stream water enhanced leaf-litter quality and led to an increase in the hyphomycete assemblage evenness and a reduction of shredder densities. However, contrary to our expectations, dissolved nutrient availability did not explain the breakdown rates. Thus, the absence of a clear effect of nutrient enrichment of stream water on the leaf breakdown rate highlights the difficulties of predicting the response of this ecosystem process to slight levels of eutrophication in headwater streams.     

Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) Signaling Regulates Mitochondrial Biogenesis and Respiration via Estrogen-related Receptor α (ERRα)

Mitochondrial abnormalities are associated with cancer development, yet how oncogenic signals affect mitochondrial functions has not been fully understood. In this study, we investigate the relationship between mitochondrial alterations and PI3K/protein kinase B (AKT) signaling activation using hepatocytes and liver tissues as our experimental models. We show here that liver-specific deletion of Pten, which leads to activation of PI3K/AKT, is associated with elevated oxidative stress, increased mitochondrial mass, and augmented respiration accompanied by enhanced glycolysis. Consistent with these observations, estrogen-related receptor α (ERRα), an orphan nuclear receptor known for its role in mitochondrial biogenesis, is up-regulated in the absence of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Our pharmacological and genetic studies show that PI3K/AKT activity regulates the expression of ERRα and mitochondrial biogenesis/respiration. Furthermore, cAMP-response element-binding protein, as a downstream target of AKT, plays a role in the regulation of ERRα, independent of PKA signaling. ERRα regulates reactive oxygen species production, and ERRα knockdown attenuates proliferation and colony-forming potential in Pten-null hepatocytes. Finally, analysis of clinical datasets from liver tissues showed a negative correlation between expressions of ERRα and PTEN in patients with liver cancer. Therefore, this study has established a previously unrecognized link between a growth signal and mitochondrial metabolism.