Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns

Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS₁₀) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10⁻¹¹; N = 467). A higher GRS₁₀ was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS₁₀ and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation.     

Molecular systematics and evolution of the Ptinidae (Coleoptera: Bostrichoidea) and related families

The Ptinidae (Coleoptera: Bostrichoidea) are a cosmopolitan, ecologically diverse, but poorly known group of Coleoptera and, excluding a few economic pests, species are rarely encountered. This first broad phylogenetic study of the Ptinidae s.l. (i.e. including both the spider beetles and anobiids) examines relationships based on DNA sequence data from two mitochondrial genes (16S and COI) and one nuclear gene (28S), using out‐group taxa from both the Bostrichidae and Dermestidae. Topologies varied depending on the genes used and whether data were analysed with either parsimony or Bayesian methods. Generally the two mitochondrial genes supported relationships near the tips of the phylogeny, whereas the nuclear gene supported the basal relationships. The monophyly of the Ptinidae was not inferred by all of the gene combinations and analysis methods, although the combined Ptinidae and Bostrichidae have a single origin in all cases. Alternative relationships include the Ptinidae s.s. (i.e. Ptininae and Gibbiinae) as sister to the anobiids (i.e. the nine remaining subfamilies of Ptinidae s.l.) + Bostrichidae, or the Bostrichidae as sister to the Ptinidae s.s.+ anobiids. Most of the larger subfamilies within the Ptinidae are not monophyletic. Further analysis with more taxa and more genes will be required to clarify and decide upon the best hypothesis of relationships found within the clades of the Bostrichidae and Ptinidae. © 2012 The Linnean Society of London, Zoological Journal of the Linnean Society, 2012, 165 , 88–108.     

siRNA against presenilin 1 (PS1) down regulates amyloid β42 production in IMR-32 cells

Background  

One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage.     

Using geophysical information to define benthic habitats in a large river

1. Most attempts to describe the distribution of benthic macroinvertebrates in large rivers have used local (grab‐scale) assessments of environmental conditions, and have had limited ability to account for spatial variation in macroinvertebrate populations. 2. We tested the ability of a habitat classification system based on multibeam bathymetry, side‐scan sonar, and chirp sub‐bottom seismics to identify large‐scale habitat units (‘facies’) and account for macroinvertebrate distribution in the Hudson River, a large tidal river in eastern New York. 3. Partial linear regression analysis showed that sediment facies were generally more effective than local or positional variables in explaining various aspects of the macroinvertebrate community (community structure, density of all invertebrates, density of fish forage, density of a pest species –Dreissena polymorpha). 4. Large‐scale habitats may be effective at explaining macroinvertebrate distributions in large rivers because they are integrative and describe habitat at the spatial scales of dominant controlling processes.     

Using a 1-D mixing model to assess the potential impact of year-to-year changes in weather on the habitat of vendace (Coregonus albula) in Bassenthwaite Lake, Cumbria

1. Bassenthwaite Lake in Cumbria is one of only two English lakes containing a population of vendace (Coregonus albula). The spatial distribution and survival of this fish is strongly influenced by the temperature and oxygen content of the water. In summer, this fish moves into deeper, colder water but avoids areas where the oxygen content is low. 2. In recent years, there has been a dramatic decline in the number of vendace found in the lake, a trend that may have been exacerbated by a succession of warm summers. Bassenthwaite only becomes stably stratified during calm, warm periods when a significant proportion of the deep water becomes anoxic. 3. Here, a one dimensional (1‐D) process‐based temperature‐oxygen model is used to simulate the year‐to‐year variations in the severity of these ‘extreme events’. The model is validated using field measurements acquired in the 1990s and used to predict the range of depths accessible to the vendace. 4. An empirical, weather‐driven model is then used to ‘hindcast’ the mixing characteristics of the lake in the 1980s and estimate the proportion of the habitat lost during warm, calm summers. These simulations show that periods of stable thermal stratification have become increasingly common in recent years. In the 1980s, only one ‘extreme event’ was identified but four such events were recorded in the 1990s. 5. The results are discussed in relation to the conservation status of the species and the potential effect of climate change on its survival in the English Lake District.