| 1. |
- Aagaard Kristensen, Jeppe, et al.
(författare)
-
Development of a harmonised soil profile analytical database for Europe : A resource for supporting regional soil management
- 2019
-
Ingår i: Soil. - : Copernicus GmbH. - 2199-3971 .- 2199-398X. ; 5:2, s. 289-301
-
Tidskriftsartikel (refereegranskat)abstract
- Soil mapping is an essential method for obtaining a spatial overview of soil resources that are increasingly threatened by environmental change and population pressure. Despite recent advances in digital soil-mapping techniques based on inference, such methods are still immature for large-scale soil mapping. During the 1970s, 1980s and 1990s, soil scientists constructed a harmonised soil map of Europe (1:1 000 000) based on national soil maps. Despite this extraordinary regional overview of the spatial distribution of European soil types, crude assumptions about soil properties were necessary for translating the maps into thematic information relevant to management. To support modellers with analytical data connected to the soil map, the European Soil Bureau Network (ESBW) commissioned the development of the soil profile analytical database for Europe (SPADE) in the late 1980s. This database contains soil analytical data based on a standardised set of soil analytical methods across the European countries. Here, we review the principles adopted for developing the SPADE database during the past five decades, the work towards fulfilling the milestones of full geographic coverage for dominant soils in all the European countries (SPADE level 1) and the addition of secondary soil types (SPADE level 2). We illustrate the application of the database by showing the distribution of the root zone capacity and by estimating the soil organic carbon (SOC) stocks at a depth of 1 m for Europe to be 60×1015 g. The increased accuracy, potentially obtained by including secondary soil types (level 2), is shown in a case study to estimate SOC stocks in Denmark. Until data from systematic cross-European soil-sampling programmes have sufficient spatial coverage for reliable data interpolation, integrating national soil maps and locally assessed analytical data into a harmonised database remains a powerful resource to support soil resources management at regional and continental scales by providing a platform to guide sustainable soil management and food production.
|
|
| 2. |
- Lindberg, Staffan, 1979-
(författare)
-
Cell-penetrating peptides for oligonucleotide delivery : Design and uptake mechanisms
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of oligonucleotides for gene therapy has the potential to efficiently treat a plethora of diseases with minimal side effects. However, the use of oligonucleotides is hampered by the properties of these molecules, which make it essentially impossible for them to permeate the cellular membrane. Therefore, a great deal of research has been focused on developing delivery vectors, which can efficiently and safely deliver oligonucleotides into cells. Cell-penetrating peptides (CPPs) constitute a class of delivery vectors that have received much attention since they were discovered over 20 years ago. CPPs can deliver a wide variety of cargos into cells, such as small molecules, proteins, oligonucleotides and particles, in an efficacious and non-toxic manner.In this thesis two new CPPs for oligonucleotide delivery were designed. The purpose of the design was to create CPPs, which form stable complexes with oligonucleotides and have endosomolytic properties. The new peptides showed superior potency in intracellular oligonucleotide delivery compared to previously reported CPPs. These results demonstrate that it is possible to drastically improve the efficiency of existing CPPs with relatively simple modifications.It is well known that CPPs use endocytosis to gain entry into cells, however, why cells endocytose CPPs has never been clearly established. In this thesis we determine that several CPP:oligonucleotide complexes interact with scavenger receptors, and that this interaction leads to endocytosis. The results presented in this thesis provides a deeper understanding of how CPPs function and thereby insights how to improve CPP design.
|
|
| 3. |
- Regberg, Jakob, 1986-
(författare)
-
Cell-penetrating peptide based nanocomplexes for oligonucleotide delivery
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Oligonucleotide-based drugs hold great promise for the treatment of many types of diseases, ranging from genetic disorders to viral infections and cancer. The problem is that efficient delivery across the cell membrane is required for oligonucleotides to have their desired effect. Cell-penetrating peptides (CPPs) provide a solution to this problem. CPPs are capable of transporting cargoes such as drugs or nucleic acids for gene therapy into the cell, either by covalent conjugation to the cargo or by non-covalent complex formation. This thesis is focused on the development of a class of peptides called PepFects, peptides with fatty acid modifications capable of forming nanoparticle-sized complexes with oligonucleotides. These complexes are efficiently internalized by many different cell types and are generally non-toxic and non-immunogenic.We have developed a number of novel PepFect peptides and a quantitative structure-activity model to predict the biological effect of our peptides. In addition, the involvement of scavenger receptors class A in the endocytic uptake of PepFect complexes as well as other CPPs and polymeric transfection agents was studied. Lastly, we have developed a series of PepFect peptides for delivery across the blood-brain barrier and a model system mimicking the blood-brain barrier in order to evaluate the passage of these peptides.The general aim of this thesis is to improve the understanding of intracellular delivery of oligonucleotides with PepFect peptides from both a chemical and a biological viewpoint, and further improve the efficacy of this delivery system with the long-term goal of making it useful in clinical settings.
|
|
