D to H ratio and the origin and evolution of Titan's atmosphere

A value of 1.7 x 10(-3) has been reported for the ratio of CH3D to CH4 in the stratosphere of the saturnian moon Titan. A lower value of 6 x 10(-4) for this ratio in the deeper part of Titan's atmosphere was reported by de Bergh et al. For comparison we note that the CH3D to CH4 ratio on Saturn and Jupiter is 8.7 x 10(-5) and 6.7 x 10(-5), respectively. We estimate the uncertainties in all these observations and data reduction to be about a factor of 2. Despite these uncertainties it appears that Titan's atmosphere is enriched in deuterium by a factor of > or = 3 relative to Jupiter and Saturn. Potential causative factors examined here for this enrichment are condensation to form tropospheric methane clouds, fractionation occurring over a hypothetical CH4-C2H6 ocean and between the ocean and the clathrate crust beneath, fractionation which occurred during the formation of Titan and fractionation occurring as a result of the evolution of Titan's atmosphere. We conclude that the greater part of the observed fractionation is probably derived from the formation of Titan and the subsequent evolution of Titan's atmosphere driven by photochemistry.     

Variations in DNA elucidate molecular networks that cause disease

Identifying variations in DNA that increase susceptibility to disease is one of the primary aims of genetic studies using a forward genetics approach. However, identification of disease-susceptibility genes by means of such studies provides limited functional information on how genes lead to disease. In fact, in most cases there is an absence of functional information altogether, preventing a definitive identification of the susceptibility gene or genes. Here we develop an alternative to the classic forward genetics approach for dissecting complex disease traits where, instead of identifying susceptibility genes directly affected by variations in DNA, we identify gene networks that are perturbed by susceptibility loci and that in turn lead to disease. Application of this method to liver and adipose gene expression data generated from a segregating mouse population results in the identification of a macrophage-enriched network supported as having a causal relationship with disease traits associated with metabolic syndrome. Three genes in this network, lipoprotein lipase (Lpl), lactamase beta (Lactb) and protein phosphatase 1-like (Ppm1l), are validated as previously unknown obesity genes, strengthening the association between this network and metabolic disease traits. Our analysis provides direct experimental support that complex traits such as obesity are emergent properties of molecular networks that are modulated by complex genetic loci and environmental factors.     

The grapevine genome sequence suggests ancestral hexaploidization in major angiosperm phyla

The analysis of the first plant genomes provided unexpected evidence for genome duplication events in species that had previously been considered as true diploids on the basis of their genetics. These polyploidization events may have had important consequences in plant evolution, in particular for species radiation and adaptation and for the modulation of functional capacities. Here we report a high-quality draft of the genome sequence of grapevine (Vitis vinifera) obtained from a highly homozygous genotype. The draft sequence of the grapevine genome is the fourth one produced so far for flowering plants, the second for a woody species and the first for a fruit crop (cultivated for both fruit and beverage). Grapevine was selected because of its important place in the cultural heritage of humanity beginning during the Neolithic period. Several large expansions of gene families with roles in aromatic features are observed. The grapevine genome has not undergone recent genome duplication, thus enabling the discovery of ancestral traits and features of the genetic organization of flowering plants. This analysis reveals the contribution of three ancestral genomes to the grapevine haploid content. This ancestral arrangement is common to many dicotyledonous plants but is absent from the genome of rice, which is a monocotyledon. Furthermore, we explain the chronology of previously described whole-genome duplication events in the evolution of flowering plants.     

Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA

Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer’s disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization. We investigated the latter hypothesis using two different APP dimerization systems in HeLa cells. Dimerization caused a decreased localization of APP to the Golgi and at the plasma membrane, whereas the levels in the ER and in endosomes were increased. Furthermore, we observed via live cell imaging and biochemical analyses that APP dimerization affects its interaction with LRP1 and SorLA, suggesting that APP dimerization modulates its interplay with sorting molecules and in turn its localization and processing. Thus, pharmacological approaches targeting APP oligomerization properties might open novel strategies for treatment of AD.     

Back to the tubule: microtubule dynamics in Parkinson’s disease

Cytoskeletal homeostasis is essential for the development, survival and maintenance of an efficient nervous system. Microtubules are highly dynamic polymers important for neuronal growth, morphology, migration and polarity. In cooperation with several classes of binding proteins, microtubules regulate long-distance intracellular cargo trafficking along axons and dendrites. The importance of a delicate interplay between cytoskeletal components is reflected in several human neurodegenerative disorders linked to abnormal microtubule dynamics, including Parkinson’s disease (PD). Mounting evidence now suggests PD pathogenesis might be underlined by early cytoskeletal dysfunction. Advances in genetics have identified PD-associated mutations and variants in genes encoding various proteins affecting microtubule function including the microtubule-associated protein tau. In this review, we highlight the role of microtubules, their major posttranslational modifications and microtubule associated proteins in neuronal function. We then present key evidence on the contribution of microtubule dysfunction to PD. Finally, we discuss how regulation of microtubule dynamics with microtubule-targeting agents and deacetylase inhibitors represents a promising strategy for innovative therapeutic development.     

A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1

We performed a genome-wide association study of 19,779 nonsynonymous SNPs in 735 individuals with Crohn disease and 368 controls. A total of 7,159 of these SNPs were informative. We followed up on all 72 SNPs with P 0.4), these data suggest that the underlying biological process may be specific to Crohn disease.     

Carapace ontogeny of the bromeliad dwelling ostracod Elpidium bromeliarum Müller, 1880 (Crustacea: Ostracoda)

Ostracods have discontinuous development, marked by ecdyses, and determinate growth. Ontogenetic studies have suggested a pattern of nine postembryonic stages (eight juvenile phases and the adult) for the main freshwater ostracod superfamilies Cypridoidea, Cytheroidea and Darwinuloidea. However, cases of a supposed extra moult in the adult stage have been proposed for some ostracod species, which would amount to 10 postembryonic growth stages. One such example is Elpidium bromeliarum Müller, 1880, a cytheroidean that inhabits tank-bromeliads. The present study is aimed at investigating the ontogenetic development of E. bromeliarum using width and length measurements, as well as carapace and appendage morphology in order to test the existing hypothesis of an additional growth stage in adults of this species. Our results revealed nine postembryonic growth stages (eight juvenile and the adult), with sexual dimorphism beginning its expression in the last juvenile stage. Thus, the ontogenetic development of E. bromeliarum agrees with the overall pattern observed for podocopid ostracods and the hypothesis of 10 postembryonic growth stages was not corroborated. We argue that the inability to differentiate juveniles from adults, or different species from one another, may have misled to the assumption of an additional moult in E. bromeliarum.     

Aspects of the natural history of Leptodactylus knudseni Heyer, 1972 (Anura: Leptodactylidae) in a pristine forest in Central Amazonia,Brazil, with comments on ontogenetic variation of its tadpoles

The Leptodactylus pentadactylus species group is comprised of medium to large species of Neotropical frogs. Leptodactylus knudseni, a member of this species group, has a wide distribution throughout the Amazon Basin. Herein we describe aspects of the reproductive biology of L. knudseni and provide notes about the ontogenetic variation of its tadpoles based on a population in a non-flooded forest near Manaus, Amazonian Brazil. Amplectant pairs of L. knudseni lay foam nests in excavated basins on the edge of temporary ponds located on clay soil and at least 50 m from a stream. The tadpole development happens initially in the foam nests with access to the pond after the rain flooding the basins. Studied clutches lacked trophic eggs and tadpoles did not produce foam. Ontogenetic variations in L. knudseni tadpoles are related to size, teeth formulae and body colour. The use of excavated basins for the deposition of foam nests has been reported in several species of the L. pentadactylus group. The absence of trophic eggs and production of foam by the tadpoles differ from other species of the L. pentadactylus group. The tadpole morphology is similar to that described for other species of the group.