| 1. |
- Habel, Joachim, et al.
(author)
-
Selecting analytical tools for characterization of polymersomes in aqueous solution
- 2015
-
In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 5:97, s. 79924-79946
-
Research review (peer-reviewed)abstract
- Selecting the appropriate analytical methods for characterizing the assembly and morphology of polymer-based vesicles, or polymersomes are required to reach their full potential in biotechnology. This work presents and compares 17 different techniques for their ability to adequately report size, lamellarity, elastic properties, bilayer surface charge, thickness and polarity of polybutadiene-polyethylene oxide (PB-PEO) based polymersomes. The techniques used in this study are broadly divided into scattering techniques, visualization methods, physical and electromagnetical manipulation and sorting/purification. Of the analytical methods tested, Cryo-transmission electron microscopy and atomic force microscopy (AFM) turned out to be advantageous for polymersomes with smaller diameter than 200 nm, whereas confocal microscopy is ideal for diameters >400 nm. Polymersomes in the intermediate diameter range can be characterized using freeze fracture Cryo-scanning electron microscopy (FF-Cryo-SEM) and nanoparticle tracking analysis (NTA). Small angle X-ray scattering (SAXS) provides reliable data on bilayer thickness and internal structure, Cryo-TEM on multilamellarity. Taken together, these tools are valuable for characterizing polymersomes per se but the comparative overview is also intended to serve as a starting point for selecting methods for characterizing polymersomes with encapsulated compounds or polymersomes with incorporated biomolecules (e.g. membrane proteins).
|
|
| 2. |
- Hay-Schmidt, Anders, et al.
(author)
-
Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour
- 2017
-
In: Reproduction. - : Bioscientifica. - 1470-1626 .- 1476-3990. ; 154:2, s. 145-152
-
Journal article (peer-reviewed)abstract
- Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDNPOA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.
|
|
| 3. |
- Hedegaard, Jakob, et al.
(author)
-
Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
-
In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
-
Journal article (peer-reviewed)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
|
|
| 4. |
- Jensen, Jesper Rindom, et al.
(author)
-
Fast LCMV-Based Methods for Fundamental Frequency Estimation
- 2013
-
In: IEEE Transactions on Signal Processing. - 1053-587X. ; 61:12, s. 3159-3172
-
Journal article (peer-reviewed)abstract
- Recently, optimal linearly constrained minimum variance (LCMV) filtering methods have been applied to fundamental frequency estimation. Such estimators often yield preferable performance but suffer from being computationally cumbersome as the resulting cost functions are multimodal with narrow peaks and require matrix inversions for each point in the search grid. In this paper, we therefore consider fast implementations of LCMV-based fundamental frequency estimators, exploiting the estimators' inherently low displacement rank of the used Toeplitz-like data covariance matrices, using as such either the classic time domain averaging covariance matrix estimator, or, if aiming for an increased spectral resolution, the covariance matrix resulting from the application of the recent iterative adaptive approach (IAA). The proposed exact implementations reduce the required computational complexity with several orders of magnitude, but, as we show, further computational savings can be obtained by the adoption of an approximative IAA-based data covariance matrix estimator, reminiscent of the recently proposed Quasi-Newton IAA technique. Furthermore, it is shown how the considered pitch estimators can be efficiently updated when new observations become available. The resulting time-recursive updating can reduce the computational complexity even further. The experimental results show that the performances of the proposed methods are comparable or better than that of other competing methods in terms of spectral resolution. Finally, it is shown that the time-recursive implementations are able to track pitch fluctuations of synthetic as well as real-life signals.
|
|
| 5. |
- Scipioni, Roberto, et al.
(author)
-
Complementary analyses of aging in a commercial LiFePO4/graphite 26650 cell
- 2018
-
In: Electrochimica Acta. - : Elsevier BV. - 0013-4686 .- 1873-3859. ; 284, s. 454-468
-
Journal article (peer-reviewed)abstract
- In this work we investigate the electrode degradation mechanisms in a commercial 2.5 Ah LiFePO4/ graphite 26650 cylindrical cell. Aged and fresh electrode samples were prepared by cycling two cells respectively five and 22 k times. Subsequently the cells were disassembled in a glovebox and the electrode samples were prepared for electrochemical testing in a 3-electrode setup, and for characterization with XRD, XPS and low-kV FIB/SEM tomography. A 1 mu m thick CEI (cathode electrolyte interface) layer was observed at the electrode/electrolyte interface of the aged LiFePO4 electrode. Relative to the fresh LiFePO4 electrode, the aged electrode exhibited a larger series resistance which indicates the observed degradation layer increases the ionic resistance. In addition, micron-sized agglomerates, probably a mixture of carbonaceous material and decomposition products from the electrolyte, were observed at the electrode/electrolyte interface of the aged graphite electrode. These layers may contribute significantly to the loss of lithium inventory (LLI) in the cell, and to the loss of active material (LAM) in the graphite electrode. Low-voltage FIB/SEM tomography was used to detect local charging effects of graphite particles in the carbon electrode, an effect of poor dissipation of the electric charge to the ground after the sample interaction with the electron beam. The charging effects were primarily observed in the aged electrode and most of the locally charged particles were found to be close to the electrode/electrolyte interface, indicating a poorly percolating graphite network near this interface.
|
|
| 6. |
- Agic, Heda, et al.
(author)
-
Late Ediacaran occurrences of the organic-walled microfossils Granomarginata and flask-shaped Lagoenaforma collaris gen. et sp. nov.
- 2022
-
In: Geological Magazine. - : Cambridge University Press. - 0016-7568 .- 1469-5081. ; 159:7, s. 1071-1092
-
Journal article (peer-reviewed)abstract
- New occurrences of flask-shaped and envelope-bearing microfossils, including the predominantly Cambrian taxon Granomarginata, are reported from new localities, as well as from earlier in time (Ediacaran) than previously known. The stratigraphic range of Granomarginata extends into the Cambrian System, where it had a cosmopolitan distribution. This newly reported Ediacaran record includes areas from Norway (Baltica), Newfoundland (Avalonia) and Namibia (adjacent to the Kalahari Craton), and puts the oldest global occurrence of Granomarginata in the Indreelva Member (< 563 Ma) of the Stahpogieddi Formation on the Digermulen Peninsula, Arctic Norway. Although Granomarginata is rare within the assemblage, these new occurrences together with previously reported occurrences from India and Poland, suggest a potentially widespread palaeogeographic distribution of Granomarginata through the middle-late Ediacaran interval. A new flask-shaped microfossil Lagoenaforma collaris gen. et sp. nov. is also reported in horizons containing Granomarginata from the Stahpogieddi Formation in Norway and the Dabis Formation in Namibia, and flask-shaped fossils are also found in the Gibbett Hill Formation in Newfoundland. The Granomarginata-Lagoenaforma association, in addition to a low-diversity organic-walled microfossil assemblage, occurs in the strata postdating the Shuram carbon isotope excursion, and may eventually be of use in terminal Ediacaran biostratigraphy. These older occurrences of Granomarginata add to a growing record of body fossil taxa spanning the Ediacaran-Cambrian boundary.
|
|
| 7. |
- Agic, Heda, et al.
(author)
-
Life through an Ediacaran glaciation : Shale- and diamictite-hosted organic-walled microfossil assemblages from the late Neoproterozoic of the Tanafjorden area, northern Norway
- 2024
-
In: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier. - 0031-0182 .- 1872-616X. ; 635
-
Journal article (peer-reviewed)abstract
- New organic-walled microfossil (OWM) assemblages are reported from upper Neoproterozoic glacial and interglacial siliciclastic deposits in Finnmark, northern Norway. A nearly continuous sedimentary succession of the Vestertana Group contains two glaciogenic units, the Smalfjorden and Mortensnes formations, interpreted as end-Cryogenian Marinoan and Ediacaran glaciations, respectively. We investigated the OWM record in the Nyborg, Mortensnes, and St ' ahpogieddi formations to assess the impact of a glacial interval on the diversity of microscopic eukaryotes. A modified acid-extraction technique was applied to recover OWM from the diamictite matrix. The upper Nyborg Formation contains morphologically complex Doushantuo-Pertatataka acritarchs (DPA), restricting the age of the Nyborg Formation to early-mid Ediacaran. DPA occur below the dolostones that record a negative carbon isotope excursion correlated with the Shuram anomaly and below a glacial diamictite. A decline in species richness and compositional change is observed in the Mortensnes glacial assemblage. DPA are replaced by bacterial filaments and cell aggregates. The overlying Indreelva Member, St ' ahpogieddi Formation contains Ediacara-type biota and palaeopascichnids, but only a depauperate OWM assemblage of leiosphaerids and flask-shaped microfossils characteristic of the late Ediacaran.The succession of assemblages in the Vestertana Group demonstrates a turnover from large eukaryotic OWM to a microbial community in the glacial interval, to a low diversity post-glacial assemblage during the rise of macroscopic life. We compared the Vestertana record to global DPA occurrences. Although one DPA assemblage zone postdates the Shuram excursion, no DPA occur above Ediacaran glacial diamictites in successions where those deposits are present. Considering this, and the community changes in the Vestertana succession, we suggest that DPA were affected by the onset of an Ediacaran glaciation. Lastly, we combined the biostratigraphic markers in the Vestertana Group to constrain the age of the Mortensnes diamictite.
|
|
| 8. |
- Ahmad, Shafqat, et al.
(author)
-
Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. : combined analysis of 111,421 individuals of European ancestry
- 2013
-
In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 9:7, s. 1003607-1003607
-
Journal article (peer-reviewed)abstract
- Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
|
|
| 9. |
- Ahmad, Shafqat, et al.
(author)
-
Gene x physical activity interactions in obesity : combined analysis of 111,421 individuals of European ancestry
- 2013
-
In: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 9:7, s. e1003607-
-
Journal article (peer-reviewed)abstract
- Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
|
|
| 10. |
- Dalgaard, Marlene D., et al.
(author)
-
A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation
- 2012
-
In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:1, s. 58-65
-
Journal article (peer-reviewed)abstract
- Background Testicular dysgenesis syndrome (TDS) is a common disease that links testicular germ cell cancer, cryptorchidism and some cases of hypospadias and male infertility with impaired development of the testis. The incidence of these disorders has increased over the last few decades, and testicular cancer now affects 1% of the Danish and Norwegian male population. Methods To identify genetic variants that span the four TDS phenotypes, the authors performed a genome-wide association study (GWAS) using Affymetrix Human SNP Array 6.0 to screen 488 patients with symptoms of TDS and 439 selected controls with excellent reproductive health. Furthermore, they developed a novel integrative method that combines GWAS data with other TDS-relevant data types and identified additional TDS markers. The most significant findings were replicated in an independent cohort of 671 Nordic men. Results Markers located in the region of TGFBR3 and BMP7 showed association with all TDS phenotypes in both the discovery and replication cohorts. An immunohistochemistry investigation confirmed the presence of transforming growth factor beta receptor type III (TGFBR3) in peritubular and Leydig cells, in both fetal and adult testis. Single-nucleotide polymorphisms in the KITLG gene showed significant associations, but only with testicular cancer. Conclusions The association of single-nucleotide polymorphisms in the TGFBR3 and BMP7 genes, which belong to the transforming growth factor b signalling pathway, suggests a role for this pathway in the pathogenesis of TDS. Integrating data from multiple layers can highlight findings in GWAS that are biologically relevant despite having border significance at currently accepted statistical levels.
|
|
