| 1. |
- Svensson, Marie, et al.
(författare)
-
Osmotic stability of the cell membrane of Escherichia coli from a temperature-limited fed-batch process
- 2005
-
Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 67:3, s. 345-350
-
Tidskriftsartikel (refereegranskat)abstract
- The temperature-limited fed-batch (TLFB) process is a technique where the oxygen consumption rate is controlled by a gradually declining temperature profile rather than a growth-limiting glucose-feeding profile. In Escherichia coli cultures, it has been proven to prevent an extensive release of endotoxins, i.e. lipopolysaccharides, that occurs in the glucose-limited fed-batch (GLFB) processes at specific growth rates below 0.1 h(-1). The TLFB and the GLFB process were compared to each other when applied to produce the periplasmic, constitutively expressed, enzyme beta-lactamase. The extraction of the enzyme was performed by osmotic shock. A higher production of beta-lactamase was achieved with the TLFB technique while no difference in the endotoxin release was found during the extraction procedure. Furthermore, it was found that growth at declining temperature, generated by the TLFB technique, gradually stabilizes the cytoplasmic membrane, resulting in a significantly increased product quality in the extract from the TLFB cultures in the osmotic shock treatment.
|
|
| 2. |
- Cappel, Ute B, et al.
(författare)
-
Electronic structure dynamics in a low bandgap polymer studied by time-resolved photoelectron spectroscopy.
- 2016
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 18:31, s. 21921-9
-
Tidskriftsartikel (refereegranskat)abstract
- Means to measure the temporal evolution following a photo-excitation in conjugated polymers are a key for the understanding and optimization of their function in applications such as organic solar cells. In this paper we study the electronic structure dynamics by direct pump-probe measurements of the excited electrons in such materials. Specifically, we carried out a time-resolved photoelectron spectroscopy (TRPES) study of the polymer PCPDTBT by combining an extreme ultraviolet (XUV) high harmonic generation source with a time-of-flight spectrometer. After excitation to either the 1st excited state or to a higher excited state, we follow how the electronic structure develops and relaxes on the electron binding energy scale. Specifically, we follow a less than 50 fs relaxation of the higher exited state and a 10 times slower relaxation of the 1st excited state. We corroborate the results using DFT calculations. Our study demonstrates the power of TRPES for studying photo-excited electron energetics and dynamics of solar cell materials.
|
|
| 3. |
|
|
| 4. |
- Hendrikse, Natalie, et al.
(författare)
-
Ancestral lysosomal enzymes with increased activity harbor therapeutic potential for treatment of Hunter syndrome
- 2021
-
Ingår i: ISCIENCE. - : Elsevier BV. - 2589-0042. ; 24:3
-
Tidskriftsartikel (refereegranskat)abstract
- We show the successful application of ancestral sequence reconstruction to enhance the activity of iduronate-2-sulfatase (IDS), thereby increasing its therapeutic potential for the treatment of Hunter syndrome-a lysosomal storage disease caused by impaired function of IDS. Current treatment, enzyme replacement therapy with recombinant human IDS, does not alleviate all symptoms, and an unmet medical need remains. We reconstructed putative ancestral sequences of mammalian IDS and compared them with extant IDS. Some ancestral variants displayed up to 2-fold higher activity than human IDS in in vitro assays and cleared more substrate in ex vivo experiments in patient fibroblasts. This could potentially allow for lower dosage or enhanced therapeutic effect in enzyme replacement therapy, thereby improving treatment outcomes and cost efficiency, as well as reducing treatment burden. In summary, we showed that ancestral sequence reconstruction can be applied to lysosomal enzymes that function in concert with modern enzymes and receptors in cells.
|
|
| 5. |
|
|
| 6. |
- Hendrikse, Natalie M., et al.
(författare)
-
Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia
- 2020
-
Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Phenylalanine/tyrosine ammonia-lyases (PAL/TALs) have been approved by the FDA for treatment of phenylketonuria and may harbour potential for complementary treatment of hereditary tyrosinemia Type I. Herein, we explore ancestral sequence reconstruction as an enzyme engineering tool to enhance the therapeutic potential of PAL/TALs. We reconstructed putative ancestors from fungi and compared their catalytic activity and stability to two modern fungal PAL/TALs. Surprisingly, most putative ancestors could be expressed as functional tetramers in Escherichia coli and thus retained their ability to oligomerize. All ancestral enzymes displayed increased thermostability compared to both modern enzymes, however, the increase in thermostability was accompanied by a loss in catalytic turnover. One reconstructed ancestral enzyme in particular could be interesting for further drug development, as its ratio of specific activities is more favourable towards tyrosine and it is more thermostable than both modern enzymes. Moreover, long-term stability assessment showed that this variant retained substantially more activity after prolonged incubation at 25 °C and 37 °C, as well as an increased resistance to incubation at 60 °C. Both of these factors are indicative of an extended shelf-life of biopharmaceuticals. We believe that ancestral sequence reconstruction has potential for enhancing the properties of enzyme therapeutics, especially with respect to stability. This work further illustrates that resurrection of putative ancestral oligomeric proteins is feasible and provides insight into the extent of conservation of a functional oligomerization surface area from ancestor to modern enzyme.
|
|
| 7. |
|
|
| 8. |
- Iraola, Aitor, et al.
(författare)
-
Microtomography-based Inter-Granular Network for the simulation of radionuclide diffusion and sorption in a granitic rock
- 2017
-
Ingår i: Journal of Contaminant Hydrology. - : Elsevier BV. - 0169-7722 .- 1873-6009. ; 207, s. 8-16
-
Tidskriftsartikel (refereegranskat)abstract
- Field investigation studies, conducted in the context of safety analyses of deep geological repositories for nuclear waste, have pointed out that in fractured crystalline rocks sorbing radionuclides can diffuse surprisingly long distances deep into the intact rock matrix; i.e. much longer distances than those predicted by reactive transport models based on a homogeneous description of the properties of the rock matrix. Here, we focus on cesium diffusion and use detailed micro characterisation data, based on micro computed tomography, along with a grain-scale Inter-Granular Network model, to offer a plausible explanation for the anomalously long cesium penetration profiles observed in these in-situ experiments. The sparse distribution of chemically reactive grains (i.e. grains belonging to sorbing mineral phases) is shown to have a strong control on the diffusive patterns of sorbing radionuclides. The computed penetration profiles of cesium agree well with an analytical model based on two parallel diffusive pathways. This agreement, along with visual inspection of the spatial distribution of cesium concentration, indicates that for sorbing radionuclides the medium indeed behaves as a composite system, with most of the mass being retained close to the injection boundary and a non-negligible part diffusing faster along preferential diffusive pathways.
|
|
| 9. |
- Müller, Dieter K., 1968-, et al.
(författare)
-
Making "wilderness" in a northern natural resource periphery : on restructuring and production of a pleasure periphery in northern Sweden
- 2019
-
Ingår i: The politics of Arctic resources. - London : Routledge. - 9781138040601 - 9781315174969 ; , s. 99-118
-
Bokkapitel (refereegranskat)abstract
- Chapter 6 takes up the more recently developed sector of tourism, problematizing the assumptions inherent in conceptions such as "resource periphery" and "pleasure periphery". Instead, the chapter shows that resource use and tourism may well interact, and that tourism even largely relates to mining or mining infrastructure: the extensive existence of infrastructure related to resource uses and industrial as well as post-industrial development at large can even be seen as the basis for tourists being able to access the "wilderness".
|
|
| 10. |
- Ren, Yansong, et al.
(författare)
-
A Multicontrolled Enamine Configurational Switch Undergoing Dynamic Constitutional Exchange
- 2018
-
Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 57:21, s. 6256-6260
-
Tidskriftsartikel (refereegranskat)abstract
- A multiresponsive enamine-based molecular switch is presented, in which forward/backward configurational rotation around the C=C bond could be precisely controlled by the addition of an acid/base or metal ions. Fluorescence turn-on/off effects and large Stokes shifts were observed while regulating the switching process with CuII. The enamine functionality furthermore enabled double dynamic regimes, in which configurational switching could operate in conjunction with constitutional enamine exchange of the rotor part. This behavior was used to construct a prototypical dynamic covalent switch system through enamine exchange with primary amines. The dynamic exchange process could be readily turned on/off by regulating the switch status with pH.
|
|
