| 1. |
- Memedi, Mevludin, et al.
(författare)
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Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease
- 2015
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Ingår i: IEEE journal of biomedical and health informatics. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-2194 .- 2168-2208. ; 19:6, s. 1829-1834
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.
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| 2. |
- McGinn, Steven, et al.
(författare)
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New Technologies for DNA analysis-A review of the READNA Project.
- 2016
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Ingår i: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784.
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Forskningsöversikt (refereegranskat)abstract
- The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
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| 3. |
- Wiszmeg, Andréa, et al.
(författare)
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Transforming trash to treasure Cultural ambiguity in foetal cell research
- 2021
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Ingår i: Philosophy Ethics and Humanities in Medicine. - : Springer Science and Business Media LLC. - 1747-5341. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Rich in different kind of potent cells, embryos are used in modern regenerative medicine and research. Neurobiologists today are pushing the boundaries for what can be done with embryos existing in the transitory margins of medicine. Therefore, there is a growing need to develop conceptual frameworks for interpreting the transformative cultural, biological and technical processes involving these aborted, donated and marginal embryos. This article is a contribution to this development of frameworks. Methods This article examines different emotional, cognitive and discursive strategies used by neurobiologists in a foetal cell transplantation trial in Parkinson's disease research, using cells harvested from aborted embryos. Two interviews were analysed in the light of former observations in the processing laboratories, using the anthropologist Mary Douglas's concept of pollution behaviour and the linguist, philosopher, psychoanalyst and feminist Julia Kristeva's concept of the abjective to explain and make sense of the findings. Results The findings indicate that the labour performed by the researchers in the trial work involves transforming the foetal material practically, as well as culturally, from trash to treasure. The transformation process contains different phases, and in the interview material we observed that the foetal material or cells were considered objects, subjects or rejected as abject by the researchers handling them, depending on what phase of process or practice they referred to or had experience of. As demonstrated in the analysis, it is the human origin of the cell that makes it abjective and activates pollution discourse, when the researchers talk of their practice. Conclusions The marginal and ambiguous status of the embryo that emerges in the accounts turns the scientists handling foetal cells into liminal characters in modern medicine. Focusing on how practical as well as emotional and cultural strategies and rationalizations of the researchers emerge in interview accounts, this study adds insights on the rationale of practically procuring, transforming and utilizing the foetal material to the already existing studies focused on the donations. We also discuss why the use and refinement of a tissue, around which there is practical consensus but cultural ambiguity, deserves further investigation.
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| 4. |
- Landegren, Nils, et al.
(författare)
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Transglutaminase 4 as a prostate autoantigen in male subfertility
- 2015
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 7:292
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.
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| 5. |
- Teixeira, Cristina, 1986, et al.
(författare)
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Application of a dynamic gastrointestinal in vitro model combined with a rat model to predict the digestive fate of barley dietary fibre and evaluate potential impact on hindgut fermentation
- 2017
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Ingår i: Bioactive Carbohydrates and Dietary Fibre. - : Elsevier BV. - 2212-6198. ; 9, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- Processing affects the composition, structure and physico-chemical characteristics of dietary fibres, and further changes can occur along the gastro-intestinal tract before entering the colon where undigested carbohydrates may serve as a substrate for the microbiota. To elucidate the effects of dietary fibre characteristic and the impact of processing on the digestive fate of dietary fibre components, in the stomach and the small intestine, a dynamic gastrointestinal in vitro model (TIM-1) was used. Three barley malt and one brewers’ spent grain, with different contents of soluble fibre, arabinoxylan (total and soluble), and β-glucan with varying Calcofluor average molecular weight (Mcf) and molecular weight distribution were evaluated in the in vitro model. Additionally, a rat model was used to study the colonic fermentation of the dietary fibre components in the barley products. The transit time through the stomach and small intestine of the in vitro model was slowest for barley malts with the highest content of soluble fibre and β-glucan. The β-glucan Mcf decreased with digestion time for all test meals, and the molecular weight distributions in the various barley products differed markedly. The highest β-glucan Mcf was found for Cinnamon malt, which also contained the highest proportion of soluble fibre. The hindgut fermentation of fibre and the proportions of caecal propionic acid were highest in rats fed barley products high in soluble fibre, β-glucan (content and Mcf), soluble arabinoxylan, and with slowest transit during digestion in the in vitro model.
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| 6. |
- Kanagarajan, Selvaraju, et al.
(författare)
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Production of functional human fetal hemoglobin in Nicotiana benthamiana for development of hemoglobin-based oxygen carriers
- 2021
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 184, s. 955-966
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Tidskriftsartikel (refereegranskat)abstract
- Hemoglobin-based oxygen carriers have long been pursued to meet clinical needs by using native hemoglobin (Hb) from human or animal blood, or recombinantly produced Hb, but the development has been impeded by safety and toxicity issues. Herewith we report the successful production of human fetal hemoglobin (HbF) in Nicotiana benthamiana through Agrobacterium tumefaciens-mediated transient expression. HbF is a heterotetrameric protein composed of two identical α- and two identical γ-subunits, held together by hydrophobic interactions, hydrogen bonds, and salt bridges. In our study, the α- and γ-subunits of HbF were fused in order to stabilize the α-subunits and facilitate balanced expression of α- and γ-subunits in N. benthamiana. Efficient extraction and purification methods enabled production of the recombinantly fused endotoxin-free HbF (rfHbF) in high quantity and quality. The transiently expressed rfHbF protein was identified by SDS-PAGE, Western blot and liquid chromatography-tandem mass spectrometry analyses. The purified rfHbF possessed structural and functional properties similar to native HbF, which were confirmed by biophysical, biochemical, and in vivo animal studies. The results demonstrate a high potential of plant expression systems in producing Hb products for use as blood substitutes.
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| 7. |
- Kuktaite, Ramune, et al.
(författare)
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Structure and Morphology of Wheat Gluten Films : From Polymeric Protein Aggregates toward Superstructure Arrangements
- 2011
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 12:5, s. 1438-1448
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of structure and morphology of extruded wheat gluten (WG) films showed WG protein assemblies elucidated on a range of length scales from nano (4.4 angstrom and 9 to 10 angstrom, up to 70 angstrom) to micro (10 mu m). The presence of NaOH in WG films induced a tetragonal structure with unit cell parameters, a = 51.85 angstrom and c = 40.65 angstrom, whereas NH4OH resulted in a bidimensional hexagonal close-packed (HCP) structure with a lattice parameter of 70 angstrom. In the WG films with NH4OH, a highly polymerized protein pattern with intimately mixed glutenins and gliadins bounded through SH/SS interchange reactions was found. A large content of beta-sheet structures was also found in these films, and the film structure was oriented in the extrusion direction. In conclusion, this study highlights complexities of the supramolecular structures and conformations of wheat gluten polymeric proteins in biofilms not previously reported for biobased materials.
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| 8. |
- Edger, Patrick P., et al.
(författare)
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The butterfly plant arms-race escalated by gene and genome duplications
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:27, s. 8362-8366
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Tidskriftsartikel (refereegranskat)abstract
- Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.
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| 9. |
- Andersson, Marlene, et al.
(författare)
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Biomimetic spinning of artificial spider silk from a chimeric minispidroin
- 2017
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 254
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Tidskriftsartikel (refereegranskat)abstract
- Herein we present a chimeric recombinant spider silk protein (spidroin) whose aqueous solubility equals that of native spider silk dope and a spinning device that is based solely on aqueous buffers, shear forces and lowered pH. The process recapitulates the complex molecular mechanisms that dictate native spider silk spinning and is highly efficient; spidroin from one liter of bacterial shake-flask culture is enough to spin a kilometer of the hitherto toughest as-spun artificial spider silk fiber.
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| 10. |
- Svärd, Anna, 1985-, et al.
(författare)
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Elastin levels are higher in healing tendons than in intact tendons and influence tissue compliance
- 2020
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Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 34:10, s. 13409-13418
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Tidskriftsartikel (refereegranskat)abstract
- Elastic fibers containing elastin play an important role in tendon functionality, but the knowledge on presence and function of elastin during tendon healing is limited. The aim of this study was to investigate elastin content and distribution in intact and healing Achilles tendons and to understand how elastin influence the viscoelastic properties of tendons. The right Achilles tendon was completely transected in 81 Sprague-Dawley rats. Elastin content was quantified in intact and healing tendons (7, 14, and 28 days post-surgery) and elastin distribution was visualized by immunohistochemistry at 14 days post-surgery. Degradation of elastin by elastase incubation was used to study the role of elastin on viscoelastic properties. Mechanical testing was either performed as a cyclic test (20x 10 N) or as a creep test. We found significantly higher levels of elastin in healing tendons at all time-points compared to intact tendons (4% in healing tendons 28 days post-surgery vs 2% in intact tendons). The elastin was more widely distributed throughout the extracellular matrix in the healing tendons in contrast to the intact tendon where the distribution was not so pronounced. Elastase incubation reduced the elastin levels by approximately 30% and led to a 40%-50% reduction in creep. This reduction was seen in both intact and healing tendons. Our results show that healing tendons contain more elastin and is more compliable than intact tendons. The role of elastin in tendon healing and tissue compliance indicates a protective role of elastic fibers to prevent re-injuries during early tendon healing. Plain Language Summary Tendons transfer high loads from muscles to bones during locomotion. They are primarily made by the protein collagen, a protein that provide strength to the tissues. Besides collagen, tendons also contain other building blocks such as, for example, elastic fibers. Elastic fibers contain elastin and elastin is important for the extensibility of the tendon. When a tendon is injured and ruptured the tissue heals through scar formation. This scar tissue is different from a normal intact tendon and it is important to understand how the tendons heal. Little is known about the presence and function of elastin during healing of tendon injuries. We have shown, in animal experiments, that healing tendons have higher amounts of elastin compared to intact tendons. The elastin is also spread throughout the tissue. When we reduced the levels of this protein, we discovered altered mechanical properties of the tendon. The healing tendon can normally extend quite a lot, but after elastin removal this extensibility was less obvious. The ability of the healing tissue to extend is probably important to protect the tendon from re-injuries during the first months after rupture. We therefore propose that the tendons heal with a large amount of elastin to prevent re-ruptures during early locomotion.
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