Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice

According to epidemiological studies, type‐2 diabetes increases the risk of Alzheimer’s disease. Here, we induced hyperglycaemia in mice overexpressing mutant amyloid precursor protein and presenilin‐1 (APdE9) either by cross‐breeding them with pancreatic insulin‐like growth factor 2 (IGF‐2) overexpressing mice or by feeding them with high‐fat diet. Glucose and insulin tolerance tests revealed significant hyperglycaemia in mice overexpressing IGF‐2, which was exacerbated by high‐fat diet. However, sustained hyperinsulinaemia and insulin resistance were observed only in mice co‐expressing IGF‐2 and APdE9 without correlation to insulin levels in brain. In behavioural tests in aged mice, APdE9 was associated with poor spatial learning and the combination of IGF‐2 and high‐fat diet further impaired learning. Neither high‐fat diet nor IGF‐2 increased β‐amyloid burden in the brain. In male mice, IGF‐2 increased β‐amyloid 42/40 ratio, which correlated with poor spatial learning. In contrast, inhibitory phosphorylation of glycogen synthase kinase 3β, which correlated with good spatial learning, was increased in APdE9 and IGF‐2 female mice on standard diet, but not on high‐fat diet. Interestingly, high‐fat diet altered τ isoform expression and increased phosphorylation of τ at Ser202 site in female mice regardless of genotype. These findings provide evidence for new regulatory mechanisms that link type‐2 diabetes and Alzheimer pathology.     

Sex Hormones and Sexual Function in Obese Men Losing Weight

Objective: To study the impact of a weight‐loss program on sex hormones and sexual function among 38 middle‐aged obese men (BMI ≥35 kg/m²). Research Methods and Procedures: A randomized controlled clinical trial was conducted. The treatment group (n = 19) participated in a 4‐month weight‐loss program including 10 weeks on a very‐low‐energy diet (VLED) and 17 behavior modification visits. There was no intervention in the control group (n = 19). Both groups were followed for 8 months, i.e., 22 weeks after the active weight loss in the treatment group. The outcome measures (weight, sex hormones, sexual function, leptin, and metabolic variables) were obtained at baseline and at three time‐points during follow‐up. Results: The mean weight loss in the treatment group was 21 kg at the end of the 10‐week VLED. At the end of follow‐up, the maintained weight loss was 17 kg of baseline weight. The control group was weight stable throughout the study. In the treatment group, increases in sex hormone‐binding globulin, testosterone, and high‐density lipoprotein‐cholesterol, as well as decreases in insulin and leptin, were maintained until the end of follow‐up, although with VLED, the level of several hormones and metabolic variables improved transiently during the rapid weight loss. There were no significant changes in the questionnaire scores on sexual function in either group. Discussion: We conclude that obese men lose weight and increase their serum testosterone level on a weight‐loss program with VLED and behavior modification. However, they do not change their sexual function scores.     

Exchange of CO2, CH4 and N2O between the atmosphere and two northern boreal ponds with catchments dominated by peatlands or forests

Concentrations of carbon dioxide (CO₂), methane (CH₄) and nitrous oxide (N₂O) in the water column and their exchange at the water/air interface were studied during the open water period in two freshwater ponds with different catchment characteristics in the northern boreal zone in Finland; either peatlands or coniferous upland forests dominated the catchment of the ponds. Both ponds were supersaturated with dissolved CO₂ and CH₄ with respect to the equilibrium with the atmosphere, but were close to the equilibrium with N₂O. The mean CO₂ efflux from the pond was higher in the peatland-dominated catchment (22 mg m^–2 h^–1) than in the forested catchment (0.7 mg m^–2 h^–1), whereas the mean CH₄ emissions were similar (7.6 and 3.5 mg m^–2 d^–1, respectively). The fluxes of N₂O were generally negligible. The higher CO₂ concentrations and efflux in the pond with the peatland-dominated catchment were attributed to a greater input of allochthonous carbon to that pond from its catchment due to its higher water colour and higher total organic carbon (TOC) concentration. The water pH, which also differed between the ponds, could additionally affect the CO₂ dynamics. Since the catchment characteristics can regulate aquatic carbon cycles, catchment-scale studies are needed to attain a deeper understanding of the aquatic greenhouse gas dynamics.     

Contribution of genetic and environmental effects to postural balance in older female twins.

The aim of the present study was to determine the relative roles of genetic and environmental influences on postural balance in older women. The participants were 97 monozygotic (MZ) and 102 dizygotic (DZ) female twins, aged 64-76 yr. Postural sway was measured during side-by-side stance with eyes open and eyes closed, and during semitandem stance with eyes open on a force platform. Sway data were condensed into four first-order and one second-order latent factors. The second-order factor, named balance, incorporates sway data from multiple tests and thus best describes the phenotype of postural balance. The contribution of genetic and environmental influences on the variability of the latent factors was assessed by using structural equation modeling. Additive genetic influences accounted for 35% and shared environmental influences accounted for 24% of the total variance in the balance factor. In the present study, postural balance in older women had a moderate genetic component. Genetic influences on postural balance may be mediated through gene variation in the systems that control posture. The finding that individual environmental influences accounted for almost one-half of the variance in postural balance points to the potential of targeted interventions to maintain and improve balance control in older persons.     

BODIPY-cholesterol: a new tool to visualize sterol trafficking in living cells and organisms

Analysis of sterol distribution and transport in living cells has been hampered by the lack of bright, photostable fluorescent sterol derivatives that closely resemble cholesterol. In this study, we employed atomistic simulations and experiments to characterize a cholesterol compound with fluorescent boron dipyrromethene difluoride linked to sterol carbon-24 (BODIPY-cholesterol). This probe packed in the membrane and behaved similarly to cholesterol both in normal and in cholesterol-storage disease cells and with trace amounts allowed the visualization of sterol movement in living systems. Upon injection into the yolk sac, BODIPY-cholesterol did not disturb zebrafish development and was targeted to sterol-enriched brain regions in live fish. We conclude that this new probe closely mimics the membrane partitioning and trafficking of cholesterol and, because of its excellent fluorescent properties, enables the direct monitoring of sterol movement by time-lapse imaging using trace amounts of the probe. This is, to our knowledge, the first cholesterol probe that fulfills these prerequisites.     

Biotic, Abiotic, and Management Controls on the Net Ecosystem CO2 Exchange of European Mountain Grassland Ecosystems

The net ecosystem carbon dioxide (CO₂) exchange (NEE) of nine European mountain grassland ecosystems was measured during 2002–2004 using the eddy covariance method. Overall, the availability of photosynthetically active radiation (PPFD) was the single most important abiotic influence factor for NEE. Its role changed markedly during the course of the season, PPFD being a better predictor for NEE during periods favorable for CO₂ uptake, which was spring and autumn for the sites characterized by summer droughts (southern sites) and (peak) summer for the Alpine and northern study sites. This general pattern was interrupted by grassland management practices, that is, mowing and grazing, when the variability in NEE explained by PPFD decreased in concert with the amount of aboveground biomass (BM_ag). Temperature was the abiotic influence factor that explained most of the variability in ecosystem respiration at the Alpine and northern study sites, but not at the southern sites characterized by a pronounced summer drought, where soil water availability and the amount of aboveground biomass were more or equally important. The amount of assimilating plant area was the single most important biotic variable determining the maximum ecosystem carbon uptake potential, that is, the NEE at saturating PPFD. Good correspondence, in terms of the magnitude of NEE, was observed with many (semi-) natural grasslands around the world, but not with grasslands sown on fertile soils in lowland locations, which exhibited higher maximum carbon gains at lower respiratory costs. It is concluded that, through triggering rapid changes in the amount and area of the aboveground plant matter, the timing and frequency of land management practices is crucial for the short-term sensitivity of the NEE of the investigated mountain grassland ecosystems to climatic drivers.     

Genome-wide analysis of single nucleotide polymorphisms uncovers population structure in Northern Europe

Background

Genome-wide data provide a powerful tool for inferring patterns of genetic variation and structure of human populations.

Principal Findings

In this study, we analysed almost 250,000 SNPs from a total of 945 samples from Eastern and Western Finland, Sweden, Northern Germany and Great Britain complemented with HapMap data. Small but statistically significant differences were observed between the European populations (F_ST = 0.0040, p<10⁻⁴), also between Eastern and Western Finland (F_ST = 0.0032, p<10⁻³). The latter indicated the existence of a relatively strong autosomal substructure within the country, similar to that observed earlier with smaller numbers of markers. The Germans and British were less differentiated than the Swedes, Western Finns and especially the Eastern Finns who also showed other signs of genetic drift. This is likely caused by the later founding of the northern populations, together with subsequent founder and bottleneck effects, and a smaller population size. Furthermore, our data suggest a small eastern contribution among the Finns, consistent with the historical and linguistic background of the population.

Significance

Our results warn against a priori assumptions of homogeneity among Finns and other seemingly isolated populations. Thus, in association studies in such populations, additional caution for population structure may be necessary. Our results illustrate that population history is often important for patterns of genetic variation, and that the analysis of hundreds of thousands of SNPs provides high resolution also for population genetics.     

Paired comparisons of carbon exchange between undisturbed and regenerating stands in four managed forests in Europe

The effects of harvest on European forest net ecosystem exchange (NEE) of carbon and its photosynthetic and respiratory components (GPP (gross primary production) and TER (total ecosystem respiration)) were examined by comparing four pairs of mature/harvested sites in Europe via a combination of eddy covariance measurements and empirical modeling. Three of the comparisons represented high coniferous forestry (spruce in Britain, and pines in Finland and France), while a coppice‐with‐standard oak plantation was examined in Italy. While every comparison revealed that harvesting converted a mature forest carbon sink into a carbon source of similar magnitude, the mechanisms by which this occurred were very different according to species or management practice. In Britain, Finland, and France the annual sink (source) strength for mature (clear‐cut) stands was estimated at 496 (112), 138 (239), and 222 (225) g C m^?2, respectively, with 381 (427) g C m^?2 for the mature (coppiced) stand in Italy. In all three cases of high forestry in Britain, Finland, and France, clear‐cutting crippled the photosynthetic capacity of the ecosystem – with mature (clear‐cut) GPP of 1970 (988), 1010 (363), and 1600 (602) g C m^?2– and also reduced ecosystem respiration to a lesser degree – TER of 1385 (1100), 839 (603), and 1415 (878) g C m^?2, respectively. By contrast, harvesting of the coppice oak system provoked a burst in respiration – with mature (clear‐cut) TER estimated at 1160 (2220) gC m^?2– which endured for the 3 years sampled postharvest. The harvest disturbance also reduced GPP in the coppice system – with mature (clear‐cut) GPP of 1600 (1420) g C m^?2– but to a lesser extent than in the coniferous forests, and with near‐complete recovery within a few years. Understanding the effects of harvest on the carbon balance of European forest systems is a necessary step towards characterizing carbon exchange for timberlands on large scales.