The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.     

A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis

Although feast and famine cycles illustrate that remodelling of adipose tissue in response to fluctuations in nutrient availability is essential for maintaining metabolic homeostasis, the underlying mechanisms remain poorly understood. Here we identify fibroblast growth factor 1 (FGF1) as a critical transducer in this process in mice, and link its regulation to the nuclear receptor PPARγ (peroxisome proliferator activated receptor γ), which is the adipocyte master regulator and the target of the thiazolidinedione class of insulin sensitizing drugs. FGF1 is the prototype of the 22-member FGF family of proteins and has been implicated in a range of physiological processes, including development, wound healing and cardiovascular changes. Surprisingly, FGF1 knockout mice display no significant phenotype under standard laboratory conditions. We show that FGF1 is highly induced in adipose tissue in response to a high-fat diet and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with a high-fat diet. Further analysis of adipose depots in FGF1-deficient mice revealed multiple histopathologies in the vasculature network, an accentuated inflammatory response, aberrant adipocyte size distribution and ectopic expression of pancreatic lipases. On withdrawal of the high-fat diet, this inflamed adipose tissue fails to properly resolve, resulting in extensive fat necrosis. In terms of mechanisms, we show that adipose induction of FGF1 in the fed state is regulated by PPARγ acting through an evolutionarily conserved promoter proximal PPAR response element within the FGF1 gene. The discovery of a phenotype for the FGF1 knockout mouse establishes the PPARγ–FGF1 axis as critical for maintaining metabolic homeostasis and insulin sensitization.     

Initial subduction-related magmatism in southern Alaska identified by geochemistry and zircon Hf-O isotopes

Abundant arc-type magmatic and metamorphic rocks exist on Earth today,which provide insights into the equilibrium state of the subduction process.However,magmat...     

Combining exchange rate forecasts: What is the optimal consensus measure?

In this paper a high-quality disaggregate database is utilized to examine whether individual forecasters produce efficient exchange rate predictions and also if the properties of the forecasts change when they are combined. The paper links a number of themes in the exchange rate literature and examines various methods of forecast combination. It is demonstrated, inter alia, that some forecasters are better than others, but that most are not as good as a naive no-change prediction. Combining forecasts adds to the accuracy of the predictions, but the gains mainly reflect the removal of systematic and unstable bias.     

Diplecogaster tonstricula,a new species of cleaning clingfish (Teleostei: Gobiesocidae) from the Canary Islands and Senegal,eastern Atlantic Ocean,with a review of the Diplecogaster-ctenocrypta species-group

The Diplecogaster-ctenocrypta species-group is reviewed; it comprises two species. The clingfish Diplecogaster ctenocrypta from the Canary Islands is redescribed. The new species Diplecogaster tonstricula, a facultative cleaner of other teleosts, is described on the basis of eight specimens and colour photos from Senegal and the Canary Islands, eastern Atlantic Ocean. The species is small, apparently not exceeding 23 mm total length; it is characterised by having nine dorsal-fin rays, eight anal-fin rays, 24–25 pectoral-fin rays, 14–15 principal caudal-fin rays, 13–16 rakers on third gill arch, pelvic disc without lateral papillae in region A, disc region B with two rows of weak papillae, interorbital distance 4.1–4.6 in head length, distance between disc and anus 14–17% of SL, head and body with 10–13 narrow vertical brownish bars, cheek with a white ocellus surrounded by black, and with a small black spot in the middle. The new species is compared with other species of the genus; a key to the six known species of the eastern Atlantic, Mediterranean and Black Sea and South African genus Diplecogaster is presented. A checklist is provided for the species of Diplecogaster and their synonyms.     

Potential contribution of respiration by Anabrus simplex (Mormon crickets) to net CO 2 exchange in three Great Basin ecosystems

Disturbance events can significantly influence net CO 2 exchange (NCE) in ecosystems. High densities of Anabrus simplex (Mormon crickets) periodically afflict large areas of the western USA; their sheer numbers could make them a significant source of CO 2 . We modeled cricket respiration at the ecosystem level using air and body temperatures and insect gas exchange measurements. Cricket CO 2 efflux values were compared to ecosystem CO 2 flux from eddy covariance measurements in 3 Great Basin ecosystems: a juniper woodland, a sagebrush shrubland, and a crested wheatgrass pasture. Mean respiration from Mormon crickets was 0.96 g CO 2 ? m –2 d –1 . Since Mormon crickets are present when NCE is otherwise near 0, they can potentially alter NCE between 20% (juniper woodland) and 60% (crested wheatgrass pasture). Transient pests such as Mormon crickets can be an important component of NCE.     

Association of Rhabdocline needle blight and epicormic branching in Douglas-fir

In northern Utah, Douglas-firs ( Pseudotsuga menziesii [Mirb.] Franco) with symptoms of Rhabdocline needle blight had a significantly higher frequency of epicormic branching than did healthy trees. It is not known whether Rhabdocline infection stimulates epicormy, or whether the proliferation of epicormics increases resistance to the disease.     

Regulation of microRNA biogenesis and turnover by animals and their viruses

MicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes.