| 1. |
- Franzén, Carl Johan, 1966, et al.
(författare)
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Multifeed simultaneous saccharification and fermentation enables high gravity submerged fermentation of lignocellulose.
- 2015
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Ingår i: Recent Advances in Fermentation Technology (RAFT 11), Clearwater Beach, Florida, USA, November 8-11, 2015. Oral presentation..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Today, second generation bioethanol production is becoming established in production plants across the world. In addition to its intrinsic value, the process can be viewed as a model process for biotechnological conversion of recalcitrant lignocellulosic raw materials to a range of chemicals and other products. So called High Gravity operation, i.e. fermentation at high solids loadings, represents continued development of the process towards higher product concentrations and productivities, and improved energy and water economy. We have employed a systematic, model-driven approach to the design of feeding schemes of solid substrate, active yeast adapted to the actual substrate, and enzymes to fed-batch simultaneous saccharification and co-fermentation (Multifeed SSCF) of steam-pretreated lignocellulosic materials in stirred tank reactors. With this approach, mixing problems were avoided even at water insoluble solids contents of 22%, leading to ethanol concentrations of 56 g/L within 72 hours of SSCF on wheat straw. Similar fermentation performance was verified in 10 m3 demonstration scale using wheat straw, and in lab scale on birch and spruce, using several yeast strains. The yeast was propagated in the liquid fraction obtained by press filtration of the pretreated slurry. Yet, even with such preadaptation and repeated addition of fresh cells, the viability in the SSCF dropped due to interactions between lignocellulose-derived inhibitors, the produced ethanol and the temperature. Decreasing the temperature from 35 to 30°C when the ethanol concentration reached 40-50 g/L resulted in rapid initial hydrolysis, maintained fermentation capacity, lower residual glucose and xylose and ethanol concentrations above 60 g/L.
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| 2. |
- Fällmar, David, et al.
(författare)
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The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care
- 2022
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Ingår i: Journal of neuroradiology. - : Elsevier. - 0150-9861 .- 1773-0406. ; 49:6, s. 421-427
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeA wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood.Material and methodsPatients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology.Results and conclusionsThe score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80.Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.
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| 3. |
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| 4. |
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| 5. |
- Lökk, Johan, et al.
(författare)
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Shifts in B12 opinions in primary health care of Sweden.
- 2001
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Ingår i: Scandinavian Journal of Public Health. - 1403-4948 .- 1651-1905. ; 29:2, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The diagnosis and management of vitamin B12 deficiency varies between countries and within countries. The aim of the study was to map current attitudes and values behind clinical decision-making in Swedish primary health care, which has a unique B12 tradition: two patients out of three are treated with oral high-dose cyanocobalamin. Most patients with B12-associated problems are managed in primary health care by general practitioners (GPs). METHODS: The study was designed to elucidate possible opinion shifts among GPs during the period 1996-1998. GPs (n=499), stratified and randomized, received a questionnaire with 24 statements on B12-associated clinical and laboratory problems, to be evaluated by a visuo-analogue scale. RESULTS: The majority of GPs in primary health care in Sweden accepted homocysteine and methylmalonic acid (MMA) as markers for functional deficiency of vitamin B12. The evaluation of classical markers of B12 deficiency was wary and balanced. There was a consensus of the need for B12 therapy to risk groups such as patients with atrophic gastritis or previous gastric surgery. The answers also appeared to reflect an improvement of professional knowledge and competence concerning B12-associated problems among Swedish GPs between 1996 and 1998. CONCLUSIONS: The overriding conclusion was that B12-associated opinions of Swedish GPs were stable within the period studied, with marginal improvements of knowledge and competence.
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| 6. |
- Lökk, Johan, et al.
(författare)
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Vitamin B12 in primary health care and geriatrics - attitudes, knowledge, competence.
- 2001
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 16:10, s. 987-992
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The objective of the study was to test attitudes, knowledge and competence of Swedish general practitioners and geriatricians concerning B12-associated problems in 1998. METHODS: Postal questionnaires were sent to a random sample of 485 GPs and a total sample of 613 geriatricians. The response rates were 70% in the GP group and 69% in the geriatrician group. The questionnaire contained 24 statements to be evaluated by a visuo-analogue scale. RESULTS: There were small numerical differences between the two physician groups. The geriatricians were more aware of risk groups for B12 deficiency. GPs were less categorical concerning low hit rate in the laboratory testing of clinical conclusions. There were statistical differences in both directions for statements on pitfalls in laboratory diagnostics. GPs were somewhat less prone to give risk groups prophylactic B12 therapy. CONCLUSIONS: GPs and geriatricians appeared to be familiar with the current debate on B12-associated problems, suggesting that health care quality will be unaffected by patient transfer from hospital care to primary health care. Copyright 2001 John Wiley & Sons, Ltd.
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| 7. |
- Nilsson, Mats, et al.
(författare)
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Medical intelligence in Sweden. Vitamin B12 : oral compared with parenteral?
- 2005
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Ingår i: Postgraduate medical journal. - : Oxford University Press (OUP). - 0032-5473 .- 1469-0756. ; 81:953, s. 191-193
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sweden is the only country in which oral high dose vitamin B12 has gained widespread use in the treatment of deficiency states. OBJECTIVE: The aim of the study was to describe prescribing patterns and sales statistics of vitamin B12 tablets and injections in Sweden 1990-2000.Design, setting, and sources: Official statistics of cobalamin prescriptions and sales were used. RESULTS: The use of vitamin B12 increased in Sweden 1990-2000, mainly because of an increase in the use of oral high dose vitamin B12 therapy. The experience, in statistical terms a "total investigation", comprised 1,000,000 patient years for tablets and 750,000 patient years for injections. During 2000, 13% of residents aged 70 and over were treated with vitamin B12, two of three with the tablet preparation. Most patients in Sweden requiring vitamin B12 therapy have transferred from parenteral to oral high dose vitamin B12 since 1964, when the oral preparation was introduced. CONCLUSION: The findings suggest that many patients in other post-industrial societies may also be suitable for oral vitamin B12 treatment.
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| 8. |
- Nilsson, Mats, et al.
(författare)
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Sex differences in cobalamin (vitamin B12) opinions of Swedish physicians.
- 2002
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 56:4, s. 299-303
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to elucidate possible sex differences in knowledge, competence and attitudes behind decision-making on cobalamin-associated problems (vitamin B(12)). The study was conducted by postal questionnaires to Swedish physicians in 1996-98. The participants were recruited by random sampling of general practitioners (1996, 1998), and a total sampling of geriatricians (1998). The overall response rate was 71%. The study group comprised 480 female physicians and 526 male physicians. The responses to 24 statements in the questionnaire were measured by means of visual analogue scales. Group differences were evaluated by medians and shapes of distributions. The female doctors appeared to value patient-related symptoms and signs more than male doctors. Conversely, male doctors relied on laboratory tests more than female doctors. As reflected by questionnaire answers, female doctors appeared to be more informed than male doctors on cobalamin-associated clinical problems. Group differences between the sexes were marginal from a numerical point of view. It is suggested that the statistical differences observed should be regarded as negligible until confirmed by further studies.
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| 9. |
- Novy, Vera, 1984, et al.
(författare)
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Saccharomyces cerevisiae strain comparison in glucose-xylose fermentations on defined substrates and in high-gravity SSCF: convergence in strain performance despite differences in genetic and evolutionary engineering history
- 2017
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834 .- 1754-6834. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The most advanced strains of xylose-fermenting Saccharomyces cerevisiae still utilize xylose far less efficiently than glucose, despite the extensive metabolic and evolutionary engineering applied in their development. Systematic comparison of strains across literature is difficult due to widely varying conditions used for determining key physiological parameters. Here, we evaluate an industrial and a laboratory S. cerevisiae strain, which has the assimilation of xylose via xylitol in common, but differ fundamentally in the history of their adaptive laboratory evolution development, and in the cofactor specificity of the xylose reductase (XR) and xylitol dehydrogenase (XDH). Results: In xylose and mixed glucose-xylose shaken bottle fermentations, with and without addition of inhibitorrich wheat straw hydrolyzate, the specific xylose uptake rate of KE6-12. A (0.27-1.08 g g(CDW)(-1) h(-1)) was 1.1 to twofold higher than that of IBB10B05 (0.10-0.82 g g(CDW)(-1) h(-1)). KE6-12. A further showed a 1.1 to ninefold higher glycerol yield (0.08-0.15 g g(-1)) than IBB10B05 (0.01-0.09 g g(-1)). However, the ethanol yield (0.30-0.40 g g(-1)), xylitol yield (0.080.26 g g(-1)), and maximum specific growth rate (0.04-0.27 h(-1)) were in close range for both strains. The robustness of flocculating variants of KE6-12. A (KE-Flow) and IBB10B05 (B-Flow) was analyzed in high-gravity simultaneous saccharification and co-fermentation. As in shaken bottles, KE-Flow showed faster xylose conversion and higher glycerol formation than B-Flow, but final ethanol titres (61 g L-1) and cell viability were again comparable for both strains. Conclusions: Individual specific traits, elicited by the engineering strategy, can affect global physiological parameters of S. cerevisiae in different and, sometimes, unpredictable ways. The industrial strain background and prolonged evolution history in KE6-12. A improved the specific xylose uptake rate more substantially than the superior XR, XDH, and xylulokinase activities were able to elicit in IBB10B05. Use of an engineered XR/XDH pathway in IBB10B05 resulted in a lower glycerol rather than a lower xylitol yield. However, the strain development programs were remarkably convergent in terms of the achieved overall strain performance. This highlights the importance of comparative strain evaluation to advance the engineering strategies for next-generation S. cerevisiae strain development.
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| 10. |
- Rydberg Sterner, Therese, et al.
(författare)
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The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
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Tidskriftsartikel (refereegranskat)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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| 11. |
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| 12. |
- Wallerius, Johan Gottschalk, 1709-1785
(författare)
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Dissertatio historico-chemica, de prima vinorum origine casuali, quam, suffrag. ampliss. senat. philosoph. in illustri Upsal. athenæo, præside, viro experientissimo atque celeberrimo, domino Joh. Gotschalk Wallerio ... pro gradu magisterii, publico bonorum examini submittit Olaus Nordeholm Westman, Sundsvallia-Medelpadus. In audit. Carol. maj. d. [tomrum] Junii, anni MDCCLX. H.A.M.S.
- 1760
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Wang, Ruifei, 1985, et al.
(författare)
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Kinetic modeling-based optimization of multi-feed simultaneous saccharification and co-fermentation of wheat straw for ethanol production
- 2015
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Ingår i: 37th Symposium on Biotechnology for Fuels and Chemicals, Oral presentation.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Fed-batch simultaneous saccharification and co-fermentation (SSCF) enables production of lignocellulosic ethanol with high content of water insoluble solids (WIS), and therefore high cellulose loadings (the major sugar source in lignocellulose). The viscosity of the SSCF broth and the mass/heat transfer efficiency, depend on the feeding frequency of solid substrates and the hydrolytic activities of the added cellulases. An ideal feeding scheme should avoid over-feeding which leads to mixing problems, while feeding as much substrates as possible to shorten the process time and increase the final ethanol titer. A previously developed kinetic model [1] was modified to predict the performance of cellulases on steam pre-treated wheat straw, and to decide when and how much WIS to feed in the next feeding event. With this approach, mixing problems could be completely avoided up to 22.2% WIS in lab scale stirred tank reactors, and ethanol concentrations reached 56 g/L within 72 hours of SSCF. The process was tested at demonstration scale in 10 m3 reactors, and a similar fermentation performance as that in lab scale was observed. Further feeding of solid substrate (>20% WIS) did not lead to increases in the ethanol concentration, while a substantial loss of yeast viability (colony forming unit) were observed in SSCF medium at high WIS contents. This was likely due to toxic compounds retained in the pre-treated lignocellulose. We are currently investigating different xylose fermenting Saccharomyces cerevisiae strains in the SSCF process to increase the ethanol titer further. [1] Wang et al. Bioresour. Technol., 2014
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| 14. |
- Westman, Johan, 1983, et al.
(författare)
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A FLO1 variant which yields a NewFlo phenotype
- 2015
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Ingår i: 32nd International Specialized Symposium on Yeasts, Perugia, Italy, September 13-17, 2015.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Flocculation is often utilised as means of separation of yeast cells from the product in alcoholic beverage production. Brewery type strains generally start to flocculate towards the end of the fermentation process, when sugars in the wort are depleted. In Saccharomyces cerevisiae, flocculation is governed by the FLO gene family, with FLO1 generally being the main contributor to strong, Flo1 phenotype, flocculation. S. cerevisiae CCUG 53310, isolated from a spent sulphite liquor plant, has high tolerance to fermentation inhibitors typically present in lignocellulose hydrolysates (Westman et al. 2012). Furthermore, CCUG 53310 flocculates constitutively with a Flo1 phenotype that is only marginally affected by the presence of high concentrations of mannose (see figure: circles).Using primers designed for FLO1, we isolated a flocculin gene from the genome of CCUG 53310. However, constitutive expression of the gene in the otherwise non-flocculating S. cerevisiae CEN.PK 113-7D, resulted in a strain with NewFlo phenotype flocculation, being inhibited by various sugars (see figure: squares, triangles, diamonds and stars). Nonetheless, the protein was phylogenetically closely related to Flo1p and by inverse PCR we could also show that the gene is a paralog of FLO1. Homology modelling of the N-terminal part of the protein structure revealed high structural similarities to the reported structure of the Flo5p N-terminal domain. Closer examination revealed differences in certain positions that have been reported to be important for carbohydrate binding by flocculins. Not previously reported, but of special interest due to its position in a loop flanking the carbohydrate binding site, was a glutamate residue that in the corresponding position in Flo1, 5 and 9p is a glycine. We hypothesise that this glutamate residue contributes to the observed NewFlo phenotype flocculation.
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| 15. |
- Westman, Johan, 1983, et al.
(författare)
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A novel chimaeric flocculation protein enhances flocculation in Saccharomyces cerevisiae
- 2018
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Ingår i: Metabolic Engineering Communications. - : Elsevier BV. - 2214-0301. ; 6, s. 49-55
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Tidskriftsartikel (refereegranskat)abstract
- Yeast flocculation is the reversible formation of multicellular complexes mediated by lectin-like cell wall proteins binding to neighbouring cells. Strong flocculation can improve the inhibitor tolerance and fermentation performance of yeast cells in second generation bioethanol production. The strength of flocculation increases with the size of the flocculation protein and is strain dependent. However, the large number of internal repeats in the sequence of FLO1 from Saccharomyces cerevisiae S288c makes it difficult to recombinantly express the gene to its full length. In the search for novel flocculation genes resulting in strong flocculation, we discovered a DNA sequence, FLONF, that gives NewFlo phenotype flocculation in S. cerevisiae CEN.PK 113-7D. The nucleotide sequence of the internal repeats of FLONF differed from those of FLO1. We hypothesized that a chimaeric flocculation gene made up of a FLO1 variant derived from S. cerevisiae S288c and additional repeats from FLONF from S. cerevisiae CCUG 53310 would be more stable and easier to amplify by PCR. The constructed gene, FLOw, had 22 internal repeats compared to 18 in FLO1. Expression of FLOw in otherwise non-flocculating strains led to strong flocculation. Despite the length of the gene, the cassette containing FLOw could be easily amplified and transformed into yeast strains of different genetic background, leading to strong flocculation in all cases tested. The developed gene can be used as a self-immobilization technique or to obtain rapidly sedimenting cells for application in e.g. sequential batches without need for centrifugation.
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| 16. |
- Westman, Johan, 1983, et al.
(författare)
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Current progress in high cell density yeast bioprocesses for bioethanol production
- 2015
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Ingår i: Biotechnology journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 10:8, s. 1185-1195
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Forskningsöversikt (refereegranskat)abstract
- High capital costs and low reaction rates are major challenges for establishment of fermentation-based production systems in the bioeconomy. Using high cell density cultures is an efficient way to increase the volumetric productivity of fermentation processes, thereby enabling faster and more robust processes and use of smaller reactors. In this review, we summarize recent progress in the application of high cell density yeast bioprocesses for first and second generation bioethanol production. High biomass concentrations obtained by retention of yeast cells in the reactor enables easier cell reuse, simplified product recovery and higher dilution rates in continuous processes. High local cell density cultures, in the form of encapsulated or strongly flocculating yeast, furthermore obtain increased tolerance to convertible fermentation inhibitors and utilize glucose and other sugars simultaneously, thereby overcoming two additional hurdles for second generation bioethanol production. These effects are caused by local concentration gradients due to diffusion limitations and conversion of inhibitors and sugars by the cells, which lead to low local concentrations of inhibitors and glucose. Quorum sensing may also contribute to the increased stress tolerance. Recent developments indicate that high cell density methodology, with emphasis on high local cell density, offers significant advantages for sustainable second generation bioethanol production.
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| 17. |
- Westman, Johan, 1983, et al.
(författare)
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Effects of encapsulation of microorganisms on product formation during microbial fermentations
- 2012
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 96:6, s. 1441-1454
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Forskningsöversikt (refereegranskat)abstract
- This paper reviews the latest developments in microbial products by encapsulated microorganisms in a liquid core surrounded by natural or synthetic membranes. Cells can be encapsulated in one or several steps using liquid droplet formation, pregel dissolving, coacervation, and interfacial polymerization. The use of encapsulated yeast and bacteria for fermentative production of ethanol, lactic acid, biogas, l-phenylacetylcarbinol, 1,3-propanediol, and riboflavin has been investigated. Encapsulated cells have furthermore been used for the biocatalytic conversion of chemicals. Fermentation, using encapsulated cells, offers various advantages compared to traditional cultivations, e.g., higher cell density, faster fermentation, improved tolerance of the cells to toxic media and high temperatures, and selective exclusion of toxic hydrophobic substances. However, mass transfer through the capsule membrane as well as the robustness of the capsules still challenge the utilization of encapsulated cells. The history and the current state of applying microbial encapsulation for production processes, along with the benefits and drawbacks concerning productivity and general physiology of the encapsulated cells, are discussed.
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| 18. |
- Westman, Johan, 1983, et al.
(författare)
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Encapsulation-Induced Stress Helps Saccharomyces cerevisiae Resist Convertible Lignocellulose Derived Inhibitors
- 2012
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 13:9, s. 11881-11894
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Tidskriftsartikel (refereegranskat)abstract
- The ability of macroencapsulated Saccharomyces cerevisiae CBS8066 to withstand readily and not readily in situ convertible lignocellulose-derived inhibitors was investigated in anaerobic batch cultivations. It was shown that encapsulation increased the tolerance against readily convertible furan aldehyde inhibitors and to dilute acid spruce hydrolysate, but not to organic acid inhibitors that cannot be metabolized anaerobically. Gene expression analysis showed that the protective effect arising from the encapsulation is evident also on the transcriptome level, as the expression of the stress-related genes YAP1, ATR1 and FLR1 was induced upon encapsulation. The transcript levels were increased due to encapsulation already in the medium without added inhibitors, indicating that the cells sensed low stress level arising from the encapsulation itself. We present a model, where the stress response is induced by nutrient limitation, that this helps the cells to cope with the increased stress added by a toxic medium, and that superficial cells in the capsules degrade convertible inhibitors, alleviating the inhibition for the cells deeper in the capsule.
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| 19. |
- Westman, Johan, 1983, et al.
(författare)
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Factors affecting the viability of Saccharomyces cerevisiae in Simultaneous Saccharification and co-Fermentation of pretreated wheat straw to ethanol
- 2015
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Ingår i: 32nd International Specialized Symposium on Yeasts.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The recalcitrance of lignocellulosic materials makes economic production of second generation ethanol difficult and necessitates pretreatment prior to hydrolysis and fermentation. Dilution in these steps limits the final ethanol titre reached in the fermentation, even at high yields. A higher concentration of the raw material already in the hydrolysis step is thus required to obtain good process economy. However, this also increases the amount of toxic compounds in the fermentation.Through simultaneous saccharification and co-fermentation, SSCF, with feeding of pretreated solids, higher substrate concentrations can be reached (Wang et al 2014). Yeast cells can be adapted to the material if they are propagated in fed-batch cultivation on a medium containing the liquid fraction from the pretreatment. Yet, even with such preadaptation, the activity of the cells added to our SSCF process dropped over time. To overcome this issue, we added fresh cells to the SSCF at different time points. We observed that the viability and fermentation capacity of the cells still decreased during the process. Nutrient supplementation could not help in improving the dropping viability. However, by adding ethanol to shake flask SSCF experiments we could see that the ethanol produced in the process was likely a contributing factor to the low viability. Drop tests on agar plates containing ethanol and/or pretreatment liquor, incubated at both 30°C and 35°C, further indicated that the decreased viability was an effect of the combination of the temperature in the reactor, the inhibitors in the material, and the ethanol produced in the process.Decreasing the temperature in the reactor to 30°C when the ethanol concentration reached 40-50 g L-1 resulted in rapid initial hydrolysis and maintained fermentation capacity. The residual amount of unfermented glucose and xylose at the end of the process was reduced. With the optimized process, ethanol concentrations of more than 60 g L-1 were reached. REFERENCE: Wang R, Koppram R, Olsson L, Franzén CJ (2014) Kinetic modeling of multi-feed simultaneous saccharification and co-fermentation of pretreated birch to ethanol. Bioresour Technol 172:303–311
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| 20. |
- Westman, Johan, 1983, et al.
(författare)
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Flocculation Causes Inhibitor Tolerance in Saccharomyces cerevisiae for Second-Generation Bioethanol Production
- 2014
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 1098-5336 .- 0099-2240. ; 80:22, s. 6908-6918
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Tidskriftsartikel (refereegranskat)abstract
- Yeast has long been considered the microorganism of choice for second-generation bioethanol production due to its fermentative capacity and ethanol tolerance. However, tolerance toward inhibitors derived from lignocellulosic materials is still an issue. Flocculating yeast strains often perform relatively well in inhibitory media, but inhibitor tolerance has never been clearly linked to the actual flocculation ability per se. In this study, variants of the flocculation gene FLO1 were transformed into the genome of the nonflocculating laboratory yeast strain Saccharomyces cerevisiae CEN.PK 113-7D. Three mutants with distinct differences in flocculation properties were isolated and characterized. The degree of flocculation and hydrophobicity of the cells were correlated to the length of the gene variant. The effect of different strength of flocculation on the fermentation performance of the strains was studied in defined medium with or without fermentation inhibitors, as well as in media based on dilute acid spruce hydrolysate. Strong flocculation aided against the readily convertible inhibitor furfural but not against less convertible inhibitors such as carboxylic acids. During fermentation of dilute acid spruce hydrolysate, the most strongly flocculating mutant with dense cell flocs showed significantly faster sugar consumption. The modified strain with the weakest flocculation showed a hexose consumption profile similar to the untransformed strain. These findings may explain why flocculation has evolved as a stress response and can find application in fermentation-based biorefinery processes on lignocellulosic raw materials.
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| 21. |
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| 22. |
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| 23. |
- Westman, Johan, 1983, et al.
(författare)
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Improved inhibitor tolerance and simultaneous utilisation of hexoses and pentoses during fermentation of inhibitory lignocellulose hydrolysates by yeast at high local cell density
- 2014
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Ingår i: Lignobiotech III, Concepción, Chile, 26-29 October 2014.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Issues still creating a barrier for successful commercialization of second generation bioethanol are the inhibitory compounds present in the lignocellulose derived media and the inability of Saccharomyces cerevisiae to efficiently utilise pentoses. Both of the issues have been addressed by construction of recombinant yeast strains, often in combination with evolutionary engineering. However, hexoses and pentoses are mainly fermented sequentially by these yeasts, prolonging the total fermentation time. In our research, we have shown that encapsulation of S. cerevisiae cells in semi-permeable alginate-chitosan liquid core gel capsules increased the tolerance to lignocellulose hydrolysates and specifically furan aldehydes. The potential formation of concentration gradients of these convertible inhibitors through the cell pellet inside the capsule has been given as explanation to the increased tolerance [1]. Gradients of carbohydrates in the capsules were further hypothesised to lead to an improvement in the simultaneous utilisation of hexose and pentose sugars by the cells. To verify this hypothesis we constructed and encapsulated the xylose fermenting S. cerevisiae strain CEN.PK XXX. We found that encapsulation of the strain not only increased the inhibitor tolerance of the yeast, but also promoted simultaneous utilisation of glucose and xylose. Furthermore, during the 96 hour fermentations of a medium with glucose and xylose, the encapsulated yeast consumed at least 50% more xylose compared to the suspended cells. This led to approximately 15% higher final ethanol titres in batch fermentations. As proof of concept, an inhibitory spruce hydrolysate was fermented by suspended and encapsulated cells. The suspended cells fermented the hexoses and pentoses mainly sequentially, after a long lag phase. The encapsulated yeast, on the other hand, did not display a lag phase, and consumed glucose, mannose, galactose and xylose simultaneously from the start of the batch. However, encapsulation of yeast cells in an alginate membrane would likely not be economically permissible in an industrial setting. We therefore investigated whether keeping the cells tight together would be sufficient, even without a membrane. To this end we constructed a set of flocculating yeast strains with different flocculation strengths by expression of different variants of a flocculation gene. We found that the strongest flocculating strain, forming large dense cell flocs in the batch reactor, increased the tolerance towards furfural and increased the fermentation rate in an inhibitory spruce hydrolysate, compared to the non-flocculating strain. Overall, yeast at high local cell density comes out as a promising option for production of second generation bioethanol.References.[1] J.O. Westman et al., Int. J. Mol. Sci., 13, 11881-11894, 2012.
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| 24. |
- Westman, Johan, 1983, et al.
(författare)
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Inhibitor tolerance and flocculation of a yeast strain suitable for second generation bioethanol production
- 2012
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Ingår i: Electronic Journal of Biotechnology. - : Elsevier BV. - 0717-3458. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Robust second generation bioethanol processes require microorganisms able to ferment inhibitory lignocellullosic hydrolysates. In this study, the inhibitor tolerance and flocculation characteristics of Saccharomyces cerevisiae CCUG53310 were evaluated in comparison with S. cerevisiae CBS8066. Results: The flocculating strain CCUG53310 could rapidly ferment all hexoses in dilute acid spruce hydrolysate, while CBS8066 was strongly inhibited in this medium. In synthetic inhibitory media, CCUG53310 was more tolerant to carboxylic acids and furan aldehydes, but more sensitive than CBS8066 to phenolic compounds. Despite the higher tolerance, the increase in expression of the YAP1, ATR1 and FLR1 genes, known to confer resistance to lignocellulose-derived inhibitors, was generally smaller in CCUG53310 than in CBS8066 in inhibitory media. The flocculation of CCUG53310 was linked to the expression of FLO8, FLO10 and one or more of FLO1, FLO5 or FLO9. Flocculation depended on cell wall proteins and Ca2+ ions, but was almost unaffected by other compounds and pH values typical for lignocellulosic media. Conclusions: S. cerevisiae CCUG53310 can be characterised as being very robust, with great potential for industrial fermentation of lignocellulosic hydrolysates relatively low in phenolic inhibitors.
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| 25. |
- Westman, Johan O., et al.
(författare)
-
Encapsulated vs. free yeast : A comparative proteomic study
- 2011
-
Ingår i: International PhD course in Industrial Biotechnology for lignocellulose based processes, October 16-21, Göteborg, Sweden.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In the search for a replacement for fossil fuels, due to their depletion as well as an increased concern about our environment, 2nd generation bioethanol comes out as one of the most promising alternatives. There are challenges in several steps of lignocellulose processing – especially due to the formation of for yeast inhibitory compounds during pretreatment and hydrolysis. It has previously been shown that encapsulation of the yeast in membranes made of an alginate gel enables the yeast to survive otherwise toxic hydrolysates. The physiological changes arising from encapsulation are however largely unknown, although it has been shown that the macromolecular composition of the yeast changes during prolonged cultivation. In this study we have therefore performed a comparative proteomic study of yeast grown in capsules and in suspension in anaerobic batch cultivations.
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| 26. |
- Westman, Johan O., et al.
(författare)
-
Inhibitor tolerance and flocculation : Characterization of a yeast strain suitable for 2nd generation bioethanol production
- 2011
-
Ingår i: Abstract book, Joint poster exhibition at the Dept Chemical and Biological Engineering, Chalmers University of Technology, and Dept Chemistry, University of Gothenburg. April 12, Göteborg, Sweden.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Robust second generation bioethanol processes require microorganisms able to obtain high yields and production rates while fermenting inhibiting hydrolysates. However, tolerance towards inhibitors like, carboxylic acids, furan aldehydes and phenolic compounds, is still an issue and the factors contributing to improved tolerance are not well known. In this study, the constitutively flocculating Saccharomyces cerevisiae strain CCUG 53310, with good ability to ferment toxic hydrolysates, was compared with S. cerevisiae CBS 8066 in order to characterize the mechanisms of flocculation and the fermentative performance in different inhibitory media. The flocculation of CCUG 53310 depended on cell wall proteins and was partly inhibited by mannose. The flocculating cells also exhibited a significantly higher hydrophobicity than the cells of the non-flocculating strain CBS 8066, which might contribute to the flocculation. The flocculating strain was more tolerant to carboxylic acids and furan aldehydes, but more sensitive to phenolic compounds. Surprisingly, the expression increase of YAP1, ATR1 and FLR1, known to confer resistance against lignocellulose-derived inhibitors, upon addition of various inhibitors to the fermentation medium, was less in CCUG 53310 than in CBS 8066 in most cases. This indicates that the flocculating strain experienced the cultivation conditions as less stressful. The flocculation in itself is a likely cause of this by creating subinhibitory local levels of inhibitors for most cells, allowing the cells in flocs to experience a lower collective stress level.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Westman, Johan, 1983, et al.
(författare)
-
Phenotypical and Physiological Characterization of a Flocculating Yeast Strain
- 2010
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Ingår i: Physiology of Yeast and Filamentous Fungi (PYFF4), Rotterdam, Holland, June 2010 and 2010 International Workshop on Wood Biorefinery and Tree Biotechnology, Örnsköldsvik, Sweden, June 2010.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Bioethanol from lignocellulosic materials is one of the desired alternatives to meet the increased demand of renewable fuels. However, there are challenges in several steps of lignocellulose processing, including pretreatment, hydrolysis and fermentation. Using flocculating strains in the fermentation process gives a number of advantages. For example, the cells can be accumulated in the bioreactors leading to high cell concentration and rapid fermentation. They are easily separated using sedimentation and can thus be recycled to the bioreactors. Some of these strains are also better than non-flocculating strains at tolerating the possible inhibitors in the cultivation media, such as furan aldehydes, organic acids and phenolic compounds. These inhibitors make it hard for the yeast to ferment the hydrolyzate and detoxification is often necessary. A flocculating yeast strain was isolated from a Swedish ethanol plant (Domsjö Fabriker AB) fermenting sulphite liquor, and registered at Culture Collection University of Gothenburg as CCUG 53310. It has been shown that this strain can successfully ferment lignocellulosic hydrolyzates, where freely suspended reference strains failed to assimilate any sugar.In order to understand and get the possibility to improve the fermentation, a phenotypic and physiological characterization of the yeast strain has been performed. The effect of different inhibitor classes present in hydrolyzate as well as of complete hydrolyzate, on the macromolecular composition of the yeast has been investigated. Different responses can be seen from the different inhibitor classes, providing evidence for differences in metabolism between yeast cells grown in the different media.The phenotypical studies have shown that the strain, that is constitutively flocculating, belongs to the Flo1 phenotype, meaning that its flocculation is inhibited only by mannose. It has also been shown that the flocculation is dependent on cell wall proteins, and Ca2+, suggesting calcium ion dependent proteins binding to carbohydrates in neighboring cells. The flocculating cells also exhibit a significantly higher hydrophobicity than the non-flocculating reference strain; this is a factor that might also contribute to the flocculation.
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| 34. |
- Westman, Johan, 1983, et al.
(författare)
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Proteomic analysis of the increased stress tolerance of Saccharomyces cerevisiae encapsulated in liquid core alginate-chitosan capsules
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 7:11, s. e49335-
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Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae CBS8066 encapsulated in semi-permeable alginate or alginate-chitosan liquid core capsules have been shown to have an enhanced tolerance towards complex dilute-acid lignocellulose hydrolysates and the lignocellulose-derived inhibitor furfural, as well as towards high temperatures. The underlying molecular reasons for these effects have however not been elucidated. In this study we have investigated the response of the encapsulation on the proteome level in the yeast cells, in comparison with cells grown freely in suspension under otherwise similar conditions. The proteomic analysis was performed on whole cell protein extracts using nLC-MS/MS with TMT® labelling and 2-D DIGE. 842 and 52 proteins were identified using each method, respectively. The abundances of 213 proteins were significantly different between encapsulated and suspended cells, with good correlation between the fold change ratios obtained by the two methods for proteins identified in both. Encapsulation of the yeast caused an up-regulation of glucose-repressed proteins and of both general and starvation-specific stress responses, such as the trehalose biosynthesis pathway, and down-regulation of proteins linked to growth and protein synthesis. The encapsulation leads to a lack of nutrients for cells close to the core of the capsule due to mass transfer limitations. The triggering of the stress response may be beneficial for the cells in certain conditions, for example leading to the increased tolerance towards high temperatures and certain inhibitors.
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| 35. |
- Westman, Johan, 1983, et al.
(författare)
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Scale-up of multi feed fed-batch simultaneous saccharification and co-fermentation of pretreated wheat straw to ethanol
- 2015
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Ingår i: 37th Symposium on Biotechnology for Fuels and Chemicals.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A major remaining issue with second-generation bioethanol production is the difficulty of reaching high enough titers to facilitate an overall economical process. Utilization of approximately 20% pretreated insoluble lignocellulosic material in the process is necessary to reach an often mentioned ethanol concentration of 4-5% (w/w). The viscosity at this solids concentration becomes higher than what is easily attainable in most reactor set-ups. We have designed a fed-batch simultaneous saccharification and co-fermentation (SSCF) process for ethanol production from pretreated wheat straw up to 21% water insoluble solids in a stirred tank reactor. In addition to feeding of solids at different time points, feeding of fresh cells at different time points was found to be beneficial for the process. The fed cells were adapted to the toxic environment by pre-cultivation in the liquid fraction from the pretreatment. Enzyme addition at different time points did however not improve the process, compared to addition of the same total amount in the beginning of the fed-batch. The effectiveness of the optimized process has been proven at demonstration scale in a 10 m3 SSCF reactor, reaching ethanol concentrations of 5% (w/w). A further increase was hindered by the toxicity of the medium, lowering the cells’ fermentation capacity. We have previously shown that strong flocculation can increase the ability of yeast to ferment toxic lignocellulose hydrolysates [1]. We therefore created strongly flocculating xylose fermenting Saccharomyces cerevisiae strains and are currently investigating these in the SSCF process.[1] Westman et al. Appl Environ Microbiol, 2014.
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| 36. |
- Westman, Johan, 1983, et al.
(författare)
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Sustaining fermentation in high-gravity ethanol production by feeding yeast to a temperature-profiled multifeed simultaneous saccharification and co-fermentation of wheat straw
- 2017
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834 .- 1754-6834. ; 10:213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Considerable progress is being made in ethanol production from lignocellulosic feedstocks by fermentation, but negative effects of inhibitors on fermenting microorganisms are still challenging. Feeding preadapted cells has shown positive effects by sustaining fermentation in high-gravity simultaneous saccharification and co-fermentation (SSCF). Loss of cell viability has been reported in several SSCF studies on different substrates and seems to be the main reason for the declining ethanol production toward the end of the process. Here, we investigate how the combination of yeast preadaptation and feeding, cell flocculation, and temperature reduction improves the cell viability in SSCF of steam pretreated wheat straw. Results: More than 50% cell viability was lost during the first 24 h of high-gravity SSCF. No beneficial effects of adding selected nutrients were observed in shake flask SSCF. Ethanol concentrations greater than 50 g L-1 led to significant loss of viability and prevented further fermentation in SSCF. The benefits of feeding preadapted yeast cells were marginal at later stages of SSCF. Yeast flocculation did not improve the viability but simplified cell harvest and improved the feasibility of the cell feeding strategy in demo scale. Cultivation at 30 °C instead of 35 °C increased cell survival significantly on solid media containing ethanol and inhibitors. Similarly, in multifeed SSCF, cells maintained the viability and fermentation capacity when the temperature was reduced from 35 to 30 °C during the process, but hydrolysis yields were compromised. By combining the yeast feeding and temperature change, an ethanol concentration of 65 g L-1, equivalent to 70% of the theoretical yield, was obtained in multifeed SSCF on pretreated wheat straw. In demo scale, the process with flocculating yeast and temperature profile resulted in 5% (w/w) ethanol, equivalent to 53% of the theoretical yield. Conclusions: Multifeed SSCF was further developed by means of a flocculating yeast and a temperature-reduction profile. Ethanol toxicity is intensified in the presence of lignocellulosic inhibitors at temperatures that are beneficial to hydrolysis in high-gravity SSCF. The counteracting effects of temperature on cell viability and hydrolysis call for more tolerant microorganisms, enzyme systems with lower temperature optimum, or full optimization of the multifeed strategy with temperature profile.
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| 37. |
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| 38. |
- Westman, Johan, 1983, et al.
(författare)
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Together we are strong! Inhibitor tolerance conferred by good neighbors?
- 2010
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Ingår i: Industrial Systems Biology: Sustainable Production of Fuels and Chemicals, Gothenburg, Sweden, August 2010 and XVIII International Conference on Bioencapsulation, Porto, Portugal, October 2010.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Bioethanol from lignocellulosic materials is one of the desired alternatives to meet the increased demand of renewable fuels. However, there are challenges in several steps of lignocellulose processing, including pretreatment, hydrolysis and fermentation. Using flocculating strains in the fermentation process gives a number of advantages. For example, the cells can be accumulated in the bioreactors leading to high cell concentration and rapid fermentation. They are easily separated using sedimentation and can thus be recycled to the bioreactors. Some of these strains are also better than non-flocculating strains at tolerating the possible inhibitors in the cultivation media. These inhibitors make it hard for the yeast to ferment the hydrolyzate and detoxification is often necessary.A flocculating yeast strain was isolated from a Swedish ethanol plant (Domsjö Fabriker AB) fermenting sulphite liquor, and registered at Culture Collection University of Gothenburg as CCUG 53310. It has been shown that this strain can successfully ferment lignocellulosic hydrolyzates, where the freely suspended reference strain, CBS 8066, failed to assimilate any sugar. However, upon encapsulation in Ca-alginate capsules, the strain CBS 8066 was able to successfully withstand the effect of the inhibitors and ferment lignocellulosic hydrolyzate.1There are similarities between yeast cells living in large flocs and yeast living inside a capsule, such as a high local cell concentration. It is hypothesized that this greatly enhanced local biomass concentration strongly contributes to this increased tolerance, since more cells will be able to survive. That high biomass leads to a greater number of living cells have also been known for a long time.2 Further it is thought that the cells on the outside of the floc, as well as in the outer layer inside the capsule, will convert most of the inhibitors and partly die, protecting the inner lying cells.The effect of different inhibitor classes, furan aldehydes, organic acids and phenolic compounds, present in the hydrolyzate on the flocculating strain as well as the freely suspended strain was also investigated, finding that the flocculating strain was indeed a lot better at withstanding the effect of furan aldehydes and carboxylic acids. Interestingly though, the CBS 8066 strain could tolerate the presence of phenolic compounds in the growth medium significantly better. This shows that higher biomass cannot help against all inhibitors, but there are also other underlying reasons, i.e. differences in the strains, yet to be investigated.
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| 39. |
- Andersson, Sebastian, et al.
(författare)
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Establishing epistemic practices in students’ formulation of scientifically researchable questions in upper secondary science education
- 2019
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Ingår i: NOFA7 ABSTRACTS Stockholm University, 13 - 15 May 2019. ; , s. 24-24
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The development of students' capability to engage in scientific inquiry is part of the science curricula across the educational system. However, previous research shows that laboratory and practical work in science education do not necessarily develop the capability to engage in scientific inquiry or contribute to developing an understanding of the nature of inquiry. The purpose of this study is to explore how teaching activities can be designed with a specific focus to develop students' capability to formulate questions for scientific inquiry. Some science education research points to that in order for students to develop an understanding of the nature of science inquiry, teaching has to include activities explicitly focusing aspects of inquiry such as asking questions, observing and making inferences. In this study we draw on the theoretical framework of epistemic practices to analyse and design teaching with the purpose of developing students' capabilities to formulate questions for scientific inquiry. Epistemic practices refer to the ways people in a specific community propose, justify, evaluate and legitimize knowledge claims within a disciplinary framework. From this perspective, formulating scientifically researchable questions makes sense only as part of epistemic practice in relation to a motive of knowledge production. The research question is: How can epistemic practices be established in upper-secondary school science where students are invited to participate in activities of formulating researchable questions?The study was carried out as a design-based research collaboration with a research team consisting of nine science teachers and four science education researchers. Data was collected in three cycles of design, intervention and analysis of research lessons with six classes in three different upper-secondary schools. The data consists of video-recordings of student interaction while engaging in tasks of formulating researchable scientific questions. The data is analysed using the didactical model of organizing purposes; distinguishing between overarching purposes and the student-orientated purposes emerging in interaction. The results indicate that the development of students’ capabilities to formulate researchable questions is situated in the processes of interaction with peers, and the conditions for situating the formulation of questions in a practice characterised by closeness to an epistemic object and gathering of observational data. Based on the results, we argue for a shift in science education from focusing students’ views of a generic nature of science or nature of science inquiry to focussing student participation in epistemic practices of various kinds.
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| 40. |
- Andersson, Sebastian, et al.
(författare)
-
Students’ capabilities to formulate scientifically researchable questions in upper secondary science education
- 2019
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Ingår i: NOFA7 ABSTRACTS Stockholm University, 13 - 15 May 2019. ; , s. 25-25
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A goal for science education is to develop student capabilities to participate in scientific inquiry. This includes various aspects of inquiry; formulating scientifically researchable questions as well as planning, performing, analyzing and presenting science investigations. In science education practices, there is a tradition of using practical or laboratory work to illustrate science concepts; focussing correct answers and reproduction of ready-made scientific knowledge, rather than engaging students in inquiry. Previous research shows that inquiry teaching predominantly engage students in investigating science questions as formulated beforehand by the teacher or a textbook. Little attention has been paid to what might characterize the capability of formulating scientifically researchable questions in school. In this study we draw on a theoretical framework of epistemic practices. Epistemic practices refer to the ways people in a specific community propose, justify, evaluate and legitimize knowledge claims within a disciplinary framework. From this perspective, formulating and developing scientifically researchable questions makes sense only in relation to a motive of knowledge production. The aim of this study is to explore what might characterize students’ capabilities to formulate and develop scientifically researchable questions in upper secondary science education.The collected data consists of video-recordings of student interaction in group-work focussing formulating and developing scientifically researchable questions. Data was collected as part of a design-based study with six classes in three different schools. The video-recordings were transcribed in verbatim and analysed by the means of qualitative content analysis. The preliminary results suggest three themes: Formulation of scientifically researchable questions as:1) Working with the specification of the epistemic object. The theme illustrates how the students elaborated on the meaning of related scientific concepts and discussed cause and effect. 2) Specifying researchability by focussing on how to operationalize the epistemic object. The theme illustrates how the students reformulate their questions as part of a process of discussing e.g. measurability and variables.3) Making value-judgements of epistemic objects. The theme illustrates how the students distinguish between scientific and non-scientific questions and make value-judgements about relevance. The results contribute to an understanding of what the capability to engage in scientific inquiry as participation in collective epistemic work in an upper-secondary school science classroom might entail. The themes are related to the establishing of a specific scientific epistemic object. The results are discussed in relation to previous research in science education and the development of resources for teaching inquiry framing capabilities of inquiry as generic.
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| 41. |
- Badji, A., et al.
(författare)
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Cerebrospinal Fluid Biomarkers, Brain Structural and Cognitive Performances Between Normotensive and Hypertensive Controlled, Uncontrolled and Untreated 70-Year-Old Adults
- 2022
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypertension is an important risk factor for Alzheimer's disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances.Objective: The aim of the present work was to investigate the differences in cognitive performances, CSF biomarkers and magnetic resonance imaging (MRI) of brain structure between normotensive, controlled hypertensive, uncontrolled hypertensive, and untreated hypertensive older adults from the Gothenburg H70 Birth Cohort Studies.Methods: As an indicator of vascular brain pathology, we measured white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, enlarged perivascular space (epvs), and fractional anisotropy (FA). To assess markers of AD pathology/neurodegeneration, we measured hippocampal volume, temporal cortical thickness on MRI, and amyloid-beta(42), phosphorylated tau, and neurofilament light protein (NfL) in cerebrospinal fluid. Various neuropsychological tests were used to assess performances in memory, attention/processing speed, executive function, verbal fluency, and visuospatial abilities.Results: We found more white matter pathology in hypertensive compared to normotensive participants, with the highest vascular burden in uncontrolled participants (e.g., lower FA, more WMHs, and epvs). No significant difference was found in any MRI or CSF markers of AD pathology/neurodegeneration when comparing normotensive and hypertensive participants, nor among hypertensive groups. No significant difference was found in most cognitive functions between groups.Conclusion: Our results suggest that good blood pressure control may help prevent cerebrovascular pathology. In addition, hypertension may contribute to cognitive decline through its effect on cerebrovascular pathology rather than AD-related pathology. These findings suggest that hypertension is associated with MRI markers of vascular pathology in the absence of a significant decline in cognitive functions.
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| 42. |
- Björnhammer, Sebastian, et al.
(författare)
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Att designa epistemiska praktiker i nv-undervisningen - en studie om hur gymnasieelever producerar naturvetenskapligt undersökningsbara frågor
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- I läroplanen för gymnasiet betonas det i de naturvetenskapliga ämnena att undervisningen ska innefatta naturvetenskapliga arbetsmetoder som att formulera och söka svar på frågor. Holmström, Pendrill et al. (2018) beskriver dock hur besparingar och en minskad tid för gymnasiets laborationsundervisning resulterat i att reformer likt denna inte fått någon genomslagskraft i lärares planering av laborationsundervisning. Den naturvetenskapliga undervisningen öppnar sällan upp för elever att formulera och utforska egna frågor (Lunde, 2015). Stort fokus läggs istället på reproduktion av redan etablerad kunskap och “rätta svar” (Andrée, 2007). När väl ansatser görs för att utforma uppgifter som ger eleverna möjlighet att utveckla förmåga till systematiskt undersökande är det inte självklart att uppgifterna faktiskt möjliggör det. Utmaningen är att utforma uppgifter som inte bara fokuserar på att eleverna ska utveckla förmåga att använda vissa tekniker och redskap för systematiskt undersökande utan att involvera eleverna i arbete med utveckla naturvetenskaplig kunskap (Bergvall, Lavett Lagerström & Andrée, 2018). Eleverna behöver få delta i aktiviteter som syftar till att synliggöra vad som kännetecknar naturvetenskapliga praktiker (Lunde, 2015; Kelly & Licona, 2018). En förutsättning för att etablera naturvetenskaplig epistemisk undervisningspraktik är enligt Kelly (2008) att eleverna får vara med och producera nya frågor och ny kunskap. Studiens syfte är att undersöka hur epistemiska praktiker kan etableras i naturvetenskaplig undervisning på gymnasiet där elever ges möjlighet att utveckla förmågan att formulera naturvetenskapligt undersökningsbara frågor. Vi har genomfört en designbaserad studie i tre iterativa cykler i ett nära samarbete mellan nio NV-lärare och sex forskare i NV-didaktik. Cyklerna har genomförts på tre gymnasieskolor i stockholmsregionen, med 60-90 deltagande elever i respektive cykel. Empiri består av videoinspelningar och ljudupptagningar från elevgruppers diskussioner under lektionerna, samt elevers skriftligt formulerade frågor. Vi har genomfört en kvalitativ innehållsanayls (Graneheim & Lundman, 2003;2017) vilket har resulterat i en variation av kvaliteter av förmågan att formulera naturvetenskapligt undersökningsbara frågor. De preliminära resultaten visar att dessa kvaliteter, som exempelvis att förhålla sig till frågans undersökningsbarhet, och hur eleverna fick möjlighet att utveckla dessa spelade roll för huruvida kunskapsproduktion eller vanemässiga handlingar etablerades i undervisningen (jfr Eriksson & Lindberg, 2016; Knorr Cetina, 2001).
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| 43. |
- Björnhammer, Sebastian, et al.
(författare)
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Vad kan elever som kan formulera naturvetenskapligt undersökningsbara frågor?
- 2020
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Ingår i: Forskning om undervisning och lärande. - 2000-9674 .- 2001-6131. ; 8:1, s. 81-104
-
Tidskriftsartikel (refereegranskat)abstract
- Denna studie fokuserar på innebörder av att kunna formulera undersökningsbara frågor i naturvetenskap. Studien tar utgångspunkt i naturvetenskapligt undersökande som epistemiskt arbete. Den forskningsfråga som undersöks är: Vilka kvalitativa aspekter av kunnande kommer till uttryck i gymnasieelevers arbete med att formulera naturvetenskapligt undersökningsbara frågor? Studien har genomförts som en designbaserad studie med sex interventioner på gymnasiet där eleverna i den genomförda undervisningen har fått i uppgift att, i olika sammanhang, formulera undersökningsbara frågor. Data innefattar film- och ljudinspelningar och har analyserats med hjälp av kvalitativ innehållsanalys. Resultaten synliggör tre kvalitativa aspekter av att formulera undersökningsbara frågor: Precisering av det epistemiska objektet, Operationalisering av det epistemiska objektet samt Värdering av frågeställningen i relation till det epistemiska objektet.
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| 44. |
- Brinkmalm, Gunnar, et al.
(författare)
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An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid.
- 2012
-
Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1096-9888 .- 1076-5174. ; 47:5, s. 591-603
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications (PTMs) within the N-terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O-glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top-down MS-based method.
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| 45. |
- Brinkmalm-Westman, Ann, 1966, et al.
(författare)
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Explorative and targeted neuroproteomics in Alzheimer's disease.
- 2015
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Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1854:7, s. 769-778
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a progressive brain amyloidosis that injures brain regions involved in memory consolidation and other higher brain functions. Neuropathologically, the disease is characterized by accumulation of a 42 amino acid peptide called amyloid β (Aβ42) in extracellular senile plaques, intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles, and neuronal and axonal degeneration and loss. Biomarker assays capturing these pathologies have been developed for use on cerebrospinal fluid samples but there are additional molecular pathways that most likely contribute to the neurodegeneration and full clinical expression of AD. One way of learning more about AD pathogenesis is to identify novel biomarkers for these pathways and examine them in longitudinal studies of patients in different stages of the disease. Here, we discuss targeted proteomic approaches to study AD and AD-related pathologies in closer detail and explorative approaches to discover novel pathways that may contribute to the disease. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology.
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| 46. |
- Brinkmalm-Westman, Ann, 1966, et al.
(författare)
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Fluid-based proteomics targeted on pathophysiological processes and pathologies in neurodegenerative diseases.
- 2019
-
Ingår i: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 151:4, s. 417-434
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative dementias constitute a broad group of diseases in which abnormally folded proteins accumulate in specific brain regions and result in tissue reactions that eventually cause neuronal dysfunction and degeneration. Depending on where in the brain this happens, symptoms appear which may be used to classify the disorders on clinical grounds. However, brain changes in neurodegenerative dementias start to accumulate many years prior to symptom onset and there is a poor correlation between the clinical picture and what pathology that is the most likely to cause it. Thus, novel drug candidates having disease-modifying effects that is targeting the underlying pathology and changes the course of the disease needs to be defined using objective biomarker-based measures since the clinical symptoms are often non-specific and overlap between different disorders. Furthermore, the treatment should ideally be initiated as soon as symptoms are evident or when biomarkers confirm an underlying pathology (pre-clinical phase of the disease) to reduce irreversible damage to, for example, neurons, synapses and axons. Clinical trials in the pre-clinical phase bring a greater importance to biomarkers since by definition the clinical effects are difficult or slow to discern in a population that is not yet clinically affected. Here, we discuss neuropathological changes that may underlie neurodegenerative dementias, including how they can be detected and quantified using currently available biofluid-based biomarkers and how more of them could be identified using targeted proteomics approaches.
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| 47. |
- Cunningham, Janet, et al.
(författare)
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Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms
- 2022
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:6, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
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| 48. |
- Cunningham, Janet L, et al.
(författare)
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Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms.
- 2022
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 225:6, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF were associated with disease severity (p<0.05). All patients with elevated markers of CNS damage in CSF also had CSF antibodies (p=0.002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
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| 49. |
- Engblom, David, 1975-, et al.
(författare)
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Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis
- 2003
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 6:11, s. 1137-1138
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Tidskriftsartikel (refereegranskat)abstract
- We studied the febrile response in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal isomerase expressed in cytokine-sensitive brain endothelial cells. These animals showed no fever and no central prostaglandin (PG) E2 synthesis after peripheral injection of bacterial-wall lipopolysaccharide, but their pyretic capacity in response to centrally administered PGE2 was intact. Our findings identify mPGES-1 as the central switch during immune-induced pyresis and as a target for the treatment of fever and other PGE2-dependent acute phase reactions elicited by the brain.
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| 50. |
- Freerks, Per, et al.
(författare)
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Att utveckla gymnasieelevers förmåga att formulera, värdera och precisera naturvetenskapligt undersökningsbara frågor
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Tidigare forskning visar att elevers deltagande i laborationer inte självklart utvecklar förmågan till systematiskt undersökande arbete. I studien som presenteras utforskas därför hur undervisning kan bidra till att utveckla elevers förmåga att formulera naturvetenskapligt undersökningsbara frågor. Lärare från tre olika gymnasieskolor och fem ämnesdidaktiska forskare har i tre cykler tillsammans designat, implementerat och analyserat lektioner där elever engagerats i att formulera naturvetenskapligt undersökningsbara frågor. Det preliminära resultatet visar att gymnasieelever kan urskilja och diskutera flera aspekter av vad som kan känneteckna en naturvetenskapligt undersökningsbar fråga. Vidare synliggörs betydelsen av att sätta formuleringen av naturvetenskapliga frågor i relation till att också planera och genomföra en undersökning.
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