In vivo imaging of stepwise vessel occlusion in cerebral photothrombosis of mice by 19F MRI

Background

¹⁹F magnetic resonance imaging (MRI) was recently introduced as a promising technique for in vivo cell tracking. In the present study we compared ¹⁹F MRI with iron-enhanced MRI in mice with photothrombosis (PT) at 7 Tesla. PT represents a model of focal cerebral ischemia exhibiting acute vessel occlusion and delayed neuroinflammation.

Methods/Principal Findings

Perfluorocarbons (PFC) or superparamagnetic iron oxide particles (SPIO) were injected intravenously at different time points after photothrombotic infarction. While administration of PFC directly after PT induction led to a strong ¹⁹F signal throughout the entire lesion, two hours delayed application resulted in a rim-like ¹⁹F signal at the outer edge of the lesion. These findings closely resembled the distribution of signal loss on T2-weighted MRI seen after SPIO injection reflecting intravascular accumulation of iron particles trapped in vessel thrombi as confirmed histologically. By sequential administration of two chemically shifted PFC compounds 0 and 2 hours after illumination the different spatial distribution of the ¹⁹F markers (infarct core/rim) could be visualized in the same animal. When PFC were applied at day 6 the fluorine marker was only detected after long acquisition times ex vivo. SPIO-enhanced MRI showed slight signal loss in vivo which was much more prominent ex vivo indicative for neuroinflammation at this late lesion stage.

Conclusion

Our study shows that vessel occlusion can be followed in vivo by ¹⁹F and SPIO-enhanced high-field MRI while in vivo imaging of neuroinflammation remains challenging. The timing of contrast agent application was the major determinant of the underlying processes depicted by both imaging techniques. Importantly, sequential application of different PFC compounds allowed depiction of ongoing vessel occlusion from the core to the margin of the ischemic lesions in a single MRI measurement.     

Breastfeeding and Its Prospective Association with Components of the GH-IGF-Axis,Insulin Resistance and Body Adiposity Measures in Young Adulthood – Insights from Linear and Quantile Regression Analysis

Background

Breastfeeding may lower chronic disease risk by long-term effects on hormonal status and adiposity, but the relations remain uncertain.

Objective

To prospectively investigate the association of breastfeeding with the growth hormone- (GH) insulin-like growth factor- (IGF) axis, insulin sensitivity, body composition and body fat distribution in younger adulthood (18–37 years).

Design

Data from 233 (54% female) participants of a German cohort, the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, with prospective data on infant feeding were analyzed. Multivariable linear as well as quantile regression were performed with full breastfeeding (not: ≤2, short: 3–17, long: >17 weeks) as exposure and adult IGF-I, IGF binding proteins (IGFBP) -1, -2, -3, homeostasis model assessment of insulin resistance (HOMA-IR), fat mass index, fat-free mass index, and waist circumference as outcomes.

Results

After adjustment for early life and socio-economic factors, women who had been breastfed longer displayed higher adult IGFBP-2 (p_trend = 0.02) and lower values of HOMA-IR (p_trend = 0.004). Furthermore, in women breastfeeding duration was associated with a lower mean fat mass index (p_trend = 0.01), fat-free mass index (p_trend = 0.02) and waist circumference (p_trend = 0.004) in young adulthood. However, there was no relation to IGF-I, IGFBP-1 and IGFBP-3 (all p_trend>0.05). Associations for IGFBP-2 and fat mass index were more pronounced at higher, for waist circumference at very low or high percentiles of the distribution. In men, there was no consistent relation of breastfeeding with any outcome.

Conclusions

Our data suggest that breastfeeding may have long-term, favorable effects on extremes of adiposity and insulin metabolism in women, but not in men. In both sexes, breastfeeding does not seem to induce programming of the GH-IGF-axis.     

Structural basis for a new tetracycline resistance mechanism relying on the TetX monooxygenase

The flavin-dependent monooxygenase TetX confers resistance to all clinically relevant tetracyclines, including the recently approved, broad-spectrum antibiotic tigecycline (Tygacil®) which is a critical last-ditch defense against multidrug-resistant pathogens. TetX represents the first resistance mechanism against tigecycline, which circumvents both the tet-gene encoded resistances, relying on active efflux of tetracyclines, and ribosomal protection proteins. The alternative enzyme-based mechanism of TetX depends on regioselective hydroxylation of tetracycline antibiotics to 11a-hydroxy-tetracyclines. Here, we report the X-ray crystallographic structure determinations at 2.1 Å resolution of native TetX from Bacteroides thetaiotaomicron and its complexes with tetracyclines. Our crystal structures explain the extremely versatile substrate diversity of the enzyme and provide a first step towards the rational design of novel tetracycline derivatives to counter TetX-based resistance prior to emerging clinical observations.     

Selective decay of terrestrial organic carbon during transport from land to sea

Numerous studies have estimated carbon exchanges at the land–atmosphere interface, more recently also including estimates at the freshwater–atmosphere interface. Less attention has been paid to lateral carbon fluxes, in particular to the fate of terrestrial carbon during transport from soils via surface waters to the sea. Using extensive datasets on soil, lake and river mouth chemistry of the boreal/hemiboreal region we determined organic carbon (OC) stocks of the O horizon from catchment soils, annual OC transports through more than 700 lakes (OC_lakeflux) and the total annual OC transport at Sweden's 53 river mouths (OC_seaflux). We show here that a minimum of 0.03–0.87% yr^?1 of the OC soil stocks need to be exported to lakes in order to sustain the annual OC_lakeflux. Across Sweden we estimated a total OC_lakeflux of ~2.9 Mtonne yr^?1, which corresponds to ~10% of Sweden's total terrestrial net ecosystem production, and it is over 50% higher than the total OC_seaflux. The OC loss during transport to the sea follows a simple exponential decay with an OC half‐life of ~12 years. Water colour, a proxy often used for dissolved humic matter, is similarly lost exponentially but about twice as fast as OC. Thus, we found a selective loss of the coloured portion of soil‐derived OC during its transport through inland waters, prior to being discharged into the sea. The selective loss is water residence time dependent, resulting in that the faster the water flows through the landscape the less OC and colour is lost. We conclude that increases in runoff will result in less efficient losses of OC, and particularly of colour, if the time for OC transformations in the landscape shortens. Consequently, OC reaching the sea is likely to become more coloured, and less processed, which can have far‐reaching effects on biogeochemical cycles.     

Wolf (Canis lupus) feeding habits during the first eight years of its occurrence in Germany

Due to the fact that the feeding habits of large carnivores are the main contentious point when they start resettling regions they were absent from for several decades, the diet composition of the wolves in Germany was analysed from the beginning of this process. Wolves in Germany primarily feed on wild ungulates, which make up more than 96% of their diet. The dominating prey species is the roe deer (55.3%), followed by red deer (20.8%) and wild boar (17.7%). The second important food category are the leporids (2.9% of Biomass), whereas livestock makes up only 0.6% of all biomass consumed. Wolves clearly prefer hunting on juvenile to adult red deer; roe deer are not selected after their age. We found seasonal differences in the diet composition with a higher amount of wild boar in spring and winter, when a high amount of juveniles and weakened animals, respectively, are available. In the first years of the study the percentage of red deer was much higher, and the percentage of roe deer therefore was lower than the following years. The amount of wild boar in the wolf diet fluctuated most in the first three years. Diet composition remained constant during the last five years. Wolves needed less than two generations for adapting to the new conditions in the cultivated landscape of eastern Germany.     

Rates of change in physical and chemical lake variables – are they comparable between large and small lakes?

Changes over time in 16 physical and chemical variables were analysed and compared between Sweden’s largest lakes, Vättern and Vänern, and 48 smaller Swedish reference lakes during spring over the period 1984–2003. The rates of changes varied substantially among lakes and among variables, and they were clearly influenced by changes in both climate and atmospheric deposition. Rates of change of variables associated with atmospheric deposition such as sulphate concentrations were dependent on lake morphometry. This also applied to the rates of change of variables associated with climate change effects in the catchment such as calcium and magnesium concentrations. However, climate change effects could also be comparable between large and small lakes. Rates of change in physical and chemical variables directly influenced by the climate via the lake water surface, e.g., surface water temperature, and variables associated with the spring phytoplankton development such as phosphate–phosphorus and nitrate–nitrogen concentrations, were similar and therefore independent of lake morphometry. This study shows that climate change effects that act via the lake surface can be of the same order of magnitude among large and small lakes, but climate change effects that act via the catchment differ substantially in large lakes. It is essential to differentiate between these two types of climate effects in order to assess the impacts of climate change and the adaptation and vulnerability of lake ecosystems.     

The role of spatial scale and area in determining richness-altitude gradients in Swedish lake phytoplankton communities

Lake phytoplankton richness data were analyzed to reveal the effects of area and scale on the richness-elevation relationship. Lakes provide a unique opportunity to accomplish this because of their well-defined boundaries, which clearly define local communities and their habitat area. Local phytoplankton richness (alpha diversity) was found to decrease with increasing elevation, even when the effect of lake area was accounted for. This decrease coincided with a decrease in lake productivity with increasing elevation. Additionally, pairwise dissimilarity calculations suggested that isolation by distance was less important in structuring local phytoplankton richness than isolation by either elevation or environmental distance. In contrast, phytoplankton richness calculated for elevation bands (gamma diversity) showed a hump-shaped dependence on elevation, with a mid-elevation maximum, consistent with the predictions of a mid-domain null model. Moreover, mean pairwise dissimilarity within elevation bands shows compositional dissimilarity to be highest at high elevations and low environmental distances, emphasizing the isolated character of high-elevation lakes. We suggest that the form of the phytoplankton richness-elevation relationship is scale-dependent, and that geometric constraints, differences in the possibility of horizontal and vertical dispersal, environmental heterogeneity and an underlying monotonic trend in productivity, are likely to be responsible for the patterns in alpha and gamma diversity observed along elevation gradients.