The crystal structure of an ‘All Locked’ nucleic acid duplex

‘Locked nucleic acids’ (LNAs) are known to introduce enhanced bio- and thermostability into natural nucleic acids rendering them powerful tools for diagnostic and therapeutic applications. We present the 1.9 Å X-ray structure of an ‘all LNA’ duplex containing exclusively modified β-d-2′-O-4′C-methylene ribofuranose nucleotides. The helix illustrates a new type of nucleic acid geometry that contributes to the understanding of the enhanced thermostability of LNA duplexes. A notable decrease of several local and overall helical parameters like twist, roll and propeller twist influence the structure of the LNA helix and result in a widening of the major groove, a decrease in helical winding and an enlarged helical pitch. A detailed structural comparison to the previously solved RNA crystal structure with the corresponding base pair sequence underlines the differences in conformation. The surrounding water network of the RNA and the LNA helix shows a similar hydration pattern.     

An integrated approach to relate Holocene climatic, hydrological, morphological and vegetation changes in the southeastern Amazon region

The geomorphological analysis of the river Tocantins alluvial area was carried out by remote sensing techniques, jointly with studies of sedimentary facies, mineralogy and geochemistry, pollen and spores, C and N isotopes data and radiocarbon dating of a sediment core from a floodplain lake, near the river Tocantins in the southeastern Amazon region. The aim was to identify and discuss the relationship between the main geomorphological processes and climatic factors, as well as their influence on vegetation patterns. The data indicate three phases of sediment and organic matter accumulation associated with vegetation changes during the Holocene: in Phase 1 (>7760 ± 80 cal yrs b.p.), the channel was gradually being disconnected from its main course, accumulating organic matter from terrestrial woody plants; in Phase 2 (>7760 ± 80 to 5145 ± 175 cal yrs b.p.), the very low energy flows allowed the deposition of autochthonous organic mud from suspension. Herbaceous vegetation and a Mauritia palm-swamp dominated the study area, followed by an increase in the contribution of freshwater dissolved organic carbon (DOC) to the lake; Phase 3 (5145 ± 175 cal yrs b.p. until present) records the expansion of ferns and arboreal plants, and greater freshwater organic matter input into the lake with anoxic water conditions. The development of the studied lake occurred by geomorphological changes and the filling process of an abandoned channel according to hydrodynamics and vegetation changes which were probably influenced by climatic changes during the Holocene.     

Human�Cenvironment interactions in mountain rainforests: archaeobotanical evidence from central Sulawesi, Indonesia

Palaeoecology may contribute to the debate on nature conservation and the preservation of cultural heritage. Here we present two palaeo-records from the Lore Lindu Biosphere Reserve and National Park in central Sulawesi, Indonesia. The park comprises one of the largest remaining and most biodiverse mountain forests of Sulawesi. Outstanding megalithic sites reveal long-term human impact on the area. Thus, modern vegetation composition within the park has been determined by complex site histories, natural and anthropogenic. Palaeo-records from sites between 1,000 and 1,400 m a.s.l. demonstrate that human activity as well as climate variations have to be considered as the main drivers of vegetation changes in the region for the last 2,000 years. Human impact is reflected by large amounts of charred fragments in the pollen records plus low values of arboreal pollen resulting from forest clearance. The stratigraphy of one of the pollen records shows effects of a general cooling trend during the Little Ice Age (LIA). Biomass loss due to the conversion of lower montane rainforest to grassland has reduced the carbon storage potential in the area of the Lore Lindu Park. Recommendations for conservation policy that may be made from the environmental history within the biosphere reserve thus include the consideration of human influence in easily accessible areas, particularly in face of recent settlement intensification.     

Poaceae pollen grain size as a tool to distinguish past grasslands in South America: a new methodological approach

Despite the dominance of grasslands during the last glacial period, especially in South America, the highly uniform morphology of Poaceae pollen grains has so far allowed only very few palynological studies based on Poaceae pollen. In our study we compare two methods of distinguishing between South American grassland ecosystems based on quantitative morphology of Poaceae pollen grains. We investigated data sets from Páramo in southern Ecuador, Campos de Altitude and Campos in south-eastern and southern Brazil as well as data sets from the Pampa in Argentina by measuring the pollen grain length, grain width, pore diameter and annulus width. Firstly we investigated the potential influence of chemical treatment of pollen grains on pollen grain size as well as the measurement setting for defining the boundary conditions for using Poaceae pollen grains in a palaeoecological investigation. Finally the measured pollen grain parameters were analyzed by comparison of average grain length using statistical tests. This approach reveals highly significant differences in average grain size between all grassland ecosystems. Assuming that a certain grain size range can be assigned to a certain Poaceae taxon, conclusions about differences and similarities in taxa composition can be derived. We used two methods of multivariate data analysis. One uses the pollen grain parameters directly for a Principle Component Analysis (PCA). The other is an already established method in grassland ecology which defines parameter based pollen grain types to investigate similarities between grassland ecosystems. Both approaches confirm the results of the grain length analysis. In this work we demonstrate that the method we developed has the potential to provide acquisition of so far inaccessible information on spatial and temporal patterns and dynamics of South American grasslands.     

Longitudinal Assessment of High Blood Pressure in Children with Nonalcoholic Fatty Liver Disease

Objective

Nonalcoholic fatty liver disease (NAFLD) affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD.

Methods

Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks.

Results

Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003). Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m², 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively). Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05).

Conclusions

In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD.     

The influence of water level on macrophyte growth and trophic interactions in eutrophic Mediterranean shallow lakes: a mesocosm experiment with and without fish

1. Water‐level fluctuations are typical of lakes located in the semi‐arid Mediterranean region, which is characterised by warm rainy winters and hot dry summers. Ongoing climate change may exacerbate fluctuations and lead to more severe episodes of drought, so information on the effects of water level on the functioning of lake ecosystems in such regions is crucial. 2. In eutrophic Lake Eymir, Turkey, we conducted a 4‐month (summer) field experiment using cylindrical 0.8‐m‐ (low‐water‐level) and 1.6‐m‐deep (high‐water‐level) mesocosms (kept open to the sediment and atmosphere). Fish (tench, Tinca tinca, and bleak, Alburnus escherichii) were added to half of the mesocosms, while the rest were kept fishless. Ten shoots of Potamogeton pectinatus were transplanted to each mesocosm. 3. Sampling for physicochemical variables, chlorophyll a (chl‐a), zooplankton and per cent plant volume inhabited (PVI%) by macrophytes was conducted weekly during the first 5 weeks, and subsequently biweekly. Macrophytes were harvested on the last sampling date. During the course of the experiment, the water level decreased by 0.41 ± 0.06 m. 4. Throughout the experiment, fish affected zooplankton abundance (?), nutrient concentrations (+), chl‐a (+) and water clarity (?) most strongly in the low‐water‐level mesocosms and the zooplankton community shifted towards dominance of small‐sized forms. The fishless mesocosms had a higher zooplankton/phytoplankton ratio, suggesting higher grazing. 5. Greatest macrophyte growth was observed in the low‐water‐level fishless mesocosms. However, despite high nutrient concentrations and low water clarity, macrophytes were also abundant in the fish mesocosms and particularly increased following a water‐level decrease from midsummer onwards. Macrophyte growth was poor in the high‐water‐level mesocosms, even in the fishless ones with high water clarity. This was ascribed to extensive periphyton development reducing light availability for the macrophytes. 6. Our results indicate that a reduction in water level during summer may help maintain the growth of macrophytes in Mediterranean eutrophic shallow lakes, despite a strong negative effect of fish predation on water clarity. It is therefore probable that an expected negative effect of global climate change on water clarity because of eutrophication and enhanced top‐down control of fish may be, at least partly, counteracted by reduced water level, provided that physical disturbance is not severe.     

Nifedipine loaded chitosan microspheres prepared by emulsification phase-separation

A high yield of nifedipine-chitosan microspheres could be obtained using an emulsification phase-separation method. A high level of entrapment of nifedipine in the microspheres was achieved. The microspheres exhibited excellent swelling properties. Differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy confirmed that at 1.84% loading, nifedipine was dispersed molecularly. The microspheres exhibited faster release at low loadings compared to high loadings. Fitting the data to the coupled Fickian/case II equation, showed that at low loadings polymer relaxation coefficients (k₂) were high. As the polymer content increased in the microspheres, the value of n (diffusional exponent characteristic of the release mechanism) approached one, which is indicative of zero order.     

Real time in vitro studies of doxorubicin release from PHEMA nanoparticles

Background  

Many anticancer agents have poor water solubility and therefore the development of novel delivery systems for such molecules has received significant attention. Nanocarriers show great potential in delivering therapeutic agents into the targeted organs or cells and have recently emerged as a promising approach to cancer treatments. The aim of this study was to prepare and use poly-2-hydroxyethyl methacrylate (PHEMA) nanoparticles for the controlled release of the anticancer drug doxorubicin.     

Intertwined effects of climate and land use change on environmental dynamics and carbon accumulation in a mangrove‐fringed coastal lagoon in Java,Indonesia

The identification and quantification of natural carbon (C) sinks is critical to global climate change mitigation efforts. Tropical coastal wetlands are considered important in this context, yet knowledge of their dynamics and quantitative data are still scarce. In order to quantify the C accumulation rate and understand how it is influenced by land use and climate change, a palaeoecological study was conducted in the mangrove‐fringed Segara Anakan Lagoon (SAL) in Java, Indonesia. A sediment core was age‐dated and analyzed for its pollen and spore, elemental and biogeochemical compositions. The results indicate that environmental dynamics in the SAL and its C accumulation over the past 400 years were controlled mainly by climate oscillations and anthropogenic activities. The interaction of these two factors changed the lagoon's sediment supply and salinity, which consequently altered the organic matter composition and deposition in the lagoon. Four phases with varying climates were identified. While autochthonous mangrove C was a significant contributor to carbon accumulation in SAL sediments throughout all four phases, varying admixtures of terrestrial C from the hinterland also contributed, with natural mixed forest C predominating in the early phases and agriculture soil C predominating in the later phases. In this context, climate‐related precipitation changes are an overarching control, as surface water transport through rivers serves as the “delivery agent” for the outcomes of the anthropogenic impact in the catchment area into the lagoon. Amongst mangrove‐dominated ecosystems globally, the SAL is one of the most effective C sinks due to high mangrove carbon input in combination with a high allochthonous carbon input from anthropogenically enhanced sediment from the hinterland and increased preservation. Given the substantial C sequestration capacity of the SAL and other mangrove‐fringed coastal lagoons, conservation and restoration of these ecosystems is vitally important for climate change mitigation.