Effects on Cholinergic Markers in Rat Brain and Blood after Short and Prolonged Administration of Donepezil

Donepezil is a selective inhibitor of acetylcholinesterase (AChE) clinically used for treating Alzheimer’s disease. Cholinergic effects after short-term exposure of donepezil (up to 12 h) have been extensively studied in rats, but few have addressed the potential long-term effects. After 14 days administration (1×3 mg/kg, decapitation 4 h after the last injection) the cerebral acetylcholine level was increased by 35% and the AChE activity was decreased by 66% and 32% in brain and blood, respectively. No change was detected in choline acetyltransferase activity, or the levels of vesicular acetylcholine transporter, choline transporter, or muscarinic receptors. Expression of various cholinergic genes was unaffected. Preliminary results of AChE activity in human blood showed 60–97% and 43–89% of pre-exposed level after one and three days of donepezil administration (5 mg daily), respectively. In conclusion, donepezil exposure in rats at doses that do not inhibit brain AChE continuously during the day, will not lead to tolerance development. Special issue dedicated to Professor Simo Oja     

Indolizine 1-sulfonates as potent inhibitors of 15-lipoxygenase from soybeans

A number of indolizine 1-sulfonates have been prepared by cyclization of cyclopropenones with pyridines followed by trapping of the intermediate 1-indolizinol with a sulfonyl halide, and examined as inhibitors of 15-lipoxygenase (15-LO). The compounds display IC(50) values between 15 and 42 microM; all are more active than the well-known 15-LO inhibitor quercetin (IC(50) 51 microM). A wide variety of substituents are well tolerated. The enzyme inhibition was not affected by preincubation or the presence of a detergent and no significant particle formation was observed. Hence, inhibition from aggregates of indolizines, promiscuous inhibition, is highly unlikely.     

Natural occurrence of microbial sulphur oxidation by long-range electron transport in the seafloor

Recently, a novel mode of sulphur oxidation was described in marine sediments, in which sulphide oxidation in deeper anoxic layers was electrically coupled to oxygen reduction at the sediment surface. Subsequent experimental evidence identified that long filamentous bacteria belonging to the family Desulfobulbaceae likely mediated the electron transport across the centimetre-scale distances. Such long-range electron transfer challenges some long-held views in microbial ecology and could have profound implications for sulphur cycling in marine sediments. But, so far, this process of electrogenic sulphur oxidation has been documented only in laboratory experiments and so its imprint on the seafloor remains unknown. Here we show that the geochemical signature of electrogenic sulphur oxidation occurs in a variety of coastal sediment environments, including a salt marsh, a seasonally hypoxic basin, and a subtidal coastal mud plain. In all cases, electrogenic sulphur oxidation was detected together with an abundance of Desulfobulbaceae filaments. Complementary laboratory experiments in intertidal sands demonstrated that mechanical disturbance by bioturbating fauna destroys the electrogenic sulphur oxidation signal. A survey of published geochemical data and 16S rRNA gene sequences identified that electrogenic sulphide oxidation is likely present in a variety of marine sediments with high sulphide generation and restricted bioturbation, such as mangrove swamps, aquaculture areas, seasonally hypoxic basins, cold sulphide seeps and possibly hydrothermal vent environments. This study shows for the first time that electrogenic sulphur oxidation occurs in a wide range of marine sediments and that bioturbation may exert a dominant control on its natural distribution.     

Shedding light on black boxes in protein identification

Performing a well thought‐out proteomics data analysis can be a daunting task, especially for newcomers to the field. Even researchers experienced in the proteomics field can find it challenging to follow existing publication guidelines for MS‐based protein identification and characterization in detail. One of the primary goals of bioinformatics is to enable any researcher to interpret the vast amounts of data generated in modern biology, by providing user‐friendly and robust end‐user applications, clear documentation, and corresponding teaching materials. In that spirit, we here present an extensive tutorial for peptide and protein identification, available at http://compomics.com/bioinformatics‐for‐proteomics . The material is completely based on freely available and open‐source tools, and has already been used and refined at numerous international courses over the past 3 years. During this time, it has demonstrated its ability to allow even complete beginners to intuitively conduct advanced bioinformatics workflows, interpret the results, and understand their context. This tutorial is thus aimed at fully empowering users, by removing black boxes in the proteomics informatics pipeline.     

Genetic Control of Obesity and Gut Microbiota Composition in Response to High-Fat,High-Sucrose Diet in Mice

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Highlights? Detailed analysis of diet-induced obesity in more than 100 inbred mouse strains ? Identification of 11 genetic loci associated with obesity and dietary responsiveness ? Significant overlap between mouse loci with human GWAS loci for obesity ? Strain-specific shifts in gut microbiota composition in response to dietary intervention     

Forward to the north: two Euro-Mediterranean bumblebee species now cross the Arctic Circle

In recent decades, several animal and plant species have been in regression (population size decrease and geographical distribution shrinking). This loss of biodiversity can be due to various factors such as the destruction and fragmentation of habitat, urban development, pesticides or climate change. However, some species benefit from these changes and expand their distribution. Here we report observations (in 2013 and 2014) of two Euro-Mediterranean bumblebee species: Bombus terrestris for the first time and Bombus lapidarius, north of the Arctic Circle in Fennoscandia.     

Climate-Driven Ichthyoplankton Drift Model Predicts Growth of Top Predator Young

Climate variability influences seabird population dynamics in several ways including access to prey near colonies during the critical chick-rearing period. This study addresses breeding success in a Barents Sea colony of common guillemots Uria aalge where trophic conditions vary according to changes in the northward transport of warm Atlantic Water. A drift model was used to simulate interannual variations in transport of cod Gadus morhua larvae along the Norwegian coast towards their nursery grounds in the Barents Sea. The results showed that the arrival of cod larvae from southern spawning grounds had a major effect on the size of common guillemot chicks at fledging. Furthermore, the fraction of larvae from the south was positively correlated to the inflow of Atlantic Water into the Barents Sea thus clearly demonstrating the mechanisms by which climate-driven bottom-up processes influence interannual variations in reproductive success in a marine top predator.     

Genome-wide association study in Dachshund: identification of a major locus affecting intervertebral disc calcification

Intervertebral disc calcification and herniation commonly affects Dachshund where the predisposition is caused by an early onset degenerative process resulting in disc calcification. A continuous spectrum of disc degeneration is seen within and among dog breeds, suggesting a multifactorial etiology. The number of calcified discs at 2 years of age determined by a radiographic evaluation is a good indicator of the severity of disc degeneration and thus serves as a measure for the risk of developing intervertebral disc herniation. The aim of the study was to identify genetic variants associated with intervertebral disc calcification in Dachshund through a genome-wide association (GWA) study. Based on thorough radiographic examinations, 48 cases with ≥ 6 disc calcifications or surgically treated for disc herniation and 46 controls with 0-1 disc calcifications were identified. GWA using the Illumina CanineHD BeadChip identified a locus on chromosome 12 from 36.8 to 38.6 Mb with 36 markers reaching genome-wide significance (P(genome) = 0.00001-0.026). This study suggests that a major locus on chromosome 12 harbors genetic variations affecting the development of intervertebral disc calcification in Dachshund.     

Functional infertility among territorial males in two passerine species, the willow warbler Phylloscopus trochilus and the bluethroat Luscinia svecica

Information about male infertility in free-living birds is scarce, but anecdotal and circumstantial evidence suggests that it does occur regularly at a low frequency. In this paper we document three cases of azoospermia in two passerine species, the willow warbler Phylloscopus trochilus and the bluethroat Luscinia svecica at their breeding grounds in South Norway. In willow warblers, two males out of a sample of 50 territory holders had no sperm in their seminal glomera, the storage site of sperm ready for ejaculation. The two males also had very small testes. One out of 48 bluethroat males also had no sperm in the seminal glomera. This male had an extreme asymmetry of the testes, with the right testis being about twice as large as the left. He also failed to fertilize any eggs in his own nest, as well as in neighbouring nests, as revealed by microsatellite genotyping. Thus, the proportion of males without sperm seems to be at a magnitude of a few (2–4) percent in both species. These are among the first estimates of the frequency of azoospermia in wild birds. Our results indicate a significant risk for sexually monogamous females of laying unfertilized eggs, which could favour the evolution of extra-pair copulation as a fertility insurance strategy in females.