Protective copolymers for nonviral gene vectors: synthesis, vector characterization and application in gene delivery

Uncontrolled interactions of gene vectors and drug carriers in and with an in vivo environment pose serious limitations to their applicability. In order to reduce such interactions we have designed, synthesized and applied novel copolymers of poly(ethylene glycol) and reactive linkers which are derivatized with anionic peptides after copolymerization. The anionic copolymer derivatives are used to coat positively charged nonviral gene vectors by electrostatic interactions. The copolymer coat confers to polyelectrolyte colloids of DNA and polycations steric stabilization in their minimal size and prevents salt- and serum albumin-induced aggregation. Furthermore, complement activation and the interaction with serum proteins are drastically reduced or abolished in contrast to unprotected DNA complexes. The designed vectors are compatible with the intracellular steps of gene delivery and can even enhance transfection efficiency as demonstrated with various adherent and nonadherent cell lines in culture. The synthetic concept is amenable to the principles of combinatorial chemistry and the copolymeric products may be applicable beyond gene delivery in targeted drug delivery

A method for reconstructing temporal changes in vegetation functional trait composition using Holocene pollen assemblages

Methods of reconstructing changes in plant traits over long time scales are needed to understand the impact of changing environmental conditions on ecosystem processes and services. Although Holocene pollen have been extensively used to provide records of vegetation history, few studies have adopted a functional trait approach that is pertinent to changes in ecosystem processes. Here, for woody and herbaceous fen peatland communities, we use modern pollen and vegetation data combined with pollen records from Holocene deposits to reconstruct vegetation functional dynamics. The six traits chosen (measures of leaf area-to-mass ratio and leaf nutrient content) are known to modulate species’ fitness and to vary with changes in ecosystem processes. We fitted linear mixed effects models between community weighted mean (CWM) trait values of the modern pollen and vegetation to determine whether traits assigned to pollen types could be used to reconstruct traits found in the vegetation from pollen assemblages. We used relative pollen productivity (RPP) correction factors in an attempt to improve this relationship. For traits showing the best fit between modern pollen and vegetation, we applied the model to dated Holocene pollen sequences from Fenland and Romney Marsh in eastern and southern England and reconstructed temporal changes in trait composition. RPP adjustment did not improve the linear relationship between modern pollen and vegetation. Leaf nutrient traits (leaf C and N) were generally more predictable from pollen data than mass-area traits. We show that inferences about biomass accumulation and decomposition rates can be made using Holocene trait reconstructions. While it is possible to reconstruct community-level trends for some leaf traits from pollen assemblages preserved in sedimentary archives in wetlands, we show the importance of testing methods in modern systems first and encourage further development of this approach to address issues concerning the pollen-plant abundance relationship and pollen source area

Holocene-scale fire dynamics of central European temperate sprucebeech forests

This study investigated the long-term role and drivers of fire in the central European temperate sprucebeech forests from Prášilské Jezero, Czech Republic. The results illustrate the complex relationship between broad-scale climate, vegetation composition, and local human activities on fire throughout the Holocene. Biomass burning was the highest (average 3 fires/1000 years) and most severe during the early Holocene when fire resistant taxa (Pinus, Corylus and Betula) dominated. Using a Generalized Additive Model to assess the response of dominant canopy taxa to changes in biomass burning and fire severity, response curves demonstrate a positive relationship (p < 0.01) between fire resistant taxa and increases in biomass burning. Norway spruce (Picea abies) established ~10,000 cal yr BP and expanded during peak biomass burning. Response curves show a slight negative relationship with Picea and increasing biomass burning, and a positive relationship with increasing fire severity. This suggests that central European spruce forests may not be significantly impacted by fire. Regional biomass burning dramatically decreased with the expansion of fire sensitive taxa (e.g. Fagus sylvatica) ~6500 cal yr BP, yet no dramatic reduction in local fire frequency occurred. This suggests either human activities or rare fire-promoting climatic events were important in shaping local fire regimes. Fire activity peaked (6 fires/1000 years) ~2500 cal yr BP and paralleled increases in anthropogenic pollen indicators. Fagus response curves illustrates a negative (p < 0.01) relationship with increasing biomass burning and fire severity suggesting that natural Fagus forests may be increasingly vulnerable to projected increases in wildfire occurrence

Late-glacial and Holocene European pollen data

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Exploring the Ecological History of a Tropical Agroforestry Landscape Using Fossil Pollen and Charcoal Analysis from Four Sites in Western Ghats, India

Contrary to expectations, some human-modified landscapes are considered to sustain both human activities and biodiversity over the long-term. Agroforestry systems are among these landscapes where crops are planted under native shade trees. In this context, ancient agroforestry systems can provide insight into how farmers managed the landscape over time. Such insight can help to quantify the extent to which tropical forests (especially habitat-specialist trees) are responding to local and landscape-level management. Here, we extracted fossil pollen (indicator of past vegetation changes) and macroscopic charcoal (indicator of biomass burning) from four forest hollows’ sedimentary sequences in an ancient agroforestry system in Western Ghats, India. We used a mixed-modelling approach and a principal components analysis (PCA) to determine past trajectories of forest change and species composition dynamics for the last 900 years. In addition, we reconstructed the long-term forest canopy dynamics and examined the persistence of habitat-specialist trees over time. Our results show that the four sites diverged to a surprising degree in both taxa composition and dynamics. However, despite these differences, forest has persisted over 900 years under agricultural activities within agroforestry systems. This long-term analysis highlights the importance of different land-use legacies as a framework to increase the effectiveness of management across tropical agricultural lands

Cyanobacteria of the thermal spring at Pancharevo, Sofia, Bulgaria

Eight taxa of cyanobacteria were identified in the thermal spring at Pancharevo (in the Sofia basin, Bulgaria). As well as the widespread Lyngbya thermalis, Phormidesmis molle (syn. Phormidium molle), Phormidium papyraceum, Phormidium corium and Mastigocladus laminosus, four species were identified for the first time in Bulgaria: Calothrix thermalis, Gloeocapsa gelatinosa, Leibleinia epiphytica and Symploca thermalis

Sheddable Coatings for Long-Circulating Nanoparticles

Nanoparticles, such as liposomes, polymeric micelles, lipoplexes and polyplexes are frequently studied as targeted drug carrier systems. The ability of these particles to circulate in the bloodstream for a prolonged period of time is often a prerequisite for successful targeted delivery. To achieve this, hydrophilic ‘stealth’ polymers, such as poly(ethylene glycol) (PEG), are used as coating materials. Such polymers shield the particle surface and thereby reduce opsonization by blood proteins and uptake by macrophages of the mononuclear phagocyte system. Yet, after localizing in the pathological site, nanoparticles should deliver their contents in an efficient manner to achieve a sufficient therapeutic response. The polymer coating, however, may hinder drug release and target cell interaction and can therefore be an obstacle in the realization of the therapeutic response. Attempts have been made to enhance the therapeutic efficacy of sterically stabilized nanoparticles by means of shedding, i.e. a loss of the coating after arrival at the target site. Such an ‘unmasking’ process may facilitate drug release and/or target cell interaction processes. This review presents an overview of the literature regarding different shedding strategies that have been investigated for the preparation of sterically stabilized nanoparticulates. Detach mechanisms and stimuli that have been used are described

Local Application of BMP-2 Specific Plasmids in Fibrin Glue does not Promote Implant Fixation

<p>Abstract</p> <p>Background</p> <p>BMP-2 is known to accelerate fracture healing and might also enhance osseointegration and implant fixation. Application of recombinant BMP-2 has a time-limited effect. Therefore, a gene transfer approach with a steady production of BMP-2 appears to be attractive. The aim of this study was to examine the effect of locally applied BMP-2 plasmids on the bone-implant integration in a non-weight bearing rabbit tibia model using a comparatively new non-viral copolymer-protected gene vector (COPROG).</p> <p>Methods</p> <p>Sixty rabbits were divided into 4 groups. All of them received nailing of both tibiae. The verum group had the nails inserted with the COPROG vector and BMP-2 plasmids using fibrin glue as a carrier. Controls were a group with fibrin glue only and a blank group. After 28 and 56 days, these three groups were sacrificed and one tibia was randomly chosen for biomechanical testing, while the other tibia underwent histomorphometrical examination. In a fourth group, a reporter-gene was incorporated in the fibrin glue instead of the BMP-2 formula to prove that transfection was successful.</p> <p>Results</p> <p>Implant fixation strength was significantly lower after 28 and 56 days in the verum group. Histomorphometry supported the findings after 28 days, showing less bone-implant contact.</p> <p>In the fourth group, successful transfection could be confirmed by detection of the reporter-gene in 20 of 22 tibiae. But, also systemic reporter-gene expression was found in heterotopic locations, showing an undesired spreading of the locally applied gene formula.</p> <p>Conclusion</p> <p>Our results underline the transfecting capability of this vector and support the idea that BMP-2 might diminish osseointegration. Further studies are necessary to specify the exact mechanisms and the systemic effects.</p

Quaternary glacial history of the Mediterranean mountains

Glacial and periglacial landforms are widespread in the mountains of the Mediterranean region. The evidence for glacial and periglacial activity has been studied for over 120 years and it is possible to identify three phases of development in this area of research. First, a pioneer phase characterized by initial descriptive observations of glacial landforms; second, a mapping phase whereby the detailed distribution of glacial landforms and sediments have been depicted on geomorphological maps; and, third, an advanced phase characterized by detailed understanding of the geochronology of glacial sequences using radiometric dating alongside detailed sedimentological and stratigraphical analyses. It is only relatively recently that studies of glaciated mountain terrains in the Mediterranean region have reached an advanced phase and it is now clear from radiometric dating programmes that the Mediterranean mountains have been glaciated during multiple glacial cycles. The most extensive phases of glaciation appear to have occurred during the Middle Pleistocene. This represents a major shift from earlier work whereby many glacial sequences were assumed to have formed during the last cold stage. Glacial and periglacial deposits from multiple Quaternary cold stages constitute a valuable palaeoclimatic record. This is especially so in the Mediterranean mountains, since mountain glaciers in this latitudinal zone would have been particularly sensitive to changes in the global climate system. © 2006 Edward Arnold (Publishers) Ltd