| 1. |
- Marote, Ana, et al.
(författare)
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Cellular Aging Secretes : a Comparison of Bone-Marrow-Derived and Induced Mesenchymal Stem Cells and Their Secretome Over Long-Term Culture
- 2023
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Ingår i: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 2629-3269 .- 2629-3277. ; 19:1, s. 248-263
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cells (MSCs) hold promising therapeutic potential in several clinical applications, mainly due to their paracrine activity. The implementation of future secretome-based therapeutic strategies requires the use of easily accessible MSCs sources that provide high numbers of cells with homogenous characteristics. MSCs obtained from induced pluripotent stem cells (iMSCs) have been put forward as an advantageous alternative to the gold-standard tissue sources, such as bone marrow (BM-MSCs). In this study, we aimed at comparing the secretome of BM-MSCs and iMSCs over long-term culture. For that, we performed a broad characterization of both sources regarding their identity, proteomic secretome analysis, as well as replicative senescence and associated phenotypes, including its effects on MSCs secretome composition and immunomodulatory action. Our results evidence a rejuvenated phenotype of iMSCs, which is translated into a superior proliferative capacity before the induction of replicative senescence. Despite this significant difference between iMSCs and BM-MSCs proliferation, both untargeted and targeted proteomic analysis revealed a similar secretome composition for both sources in pre-senescent and senescent states. These results suggest that shifting from the use of BM-MSCs to a more advantageous source, like iMSCs, may yield similar therapeutic effects as identified over the past years for this gold-standard MSC source. Graphical Abstract: [Figure not available: see fulltext.].
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| 2. |
- Almeida, Joana R., et al.
(författare)
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Structure-Antifouling Activity Relationship and Molecular Targets of Bio-Inspired(thio)xanthones
- 2020
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- The development of alternative ecological and effective antifouling technologies is still challenging. Synthesis of nature-inspired compounds has been exploited, given the potential to assure commercial supplies of potential ecofriendly antifouling agents. In this direction, the antifouling activity of a series of nineteen synthetic small molecules, with chemical similarities with natural products, were exploited in this work. Six (4,5,7,10,15and17) of the tested xanthones showed in vivo activity toward the settlement ofMytilus galloprovincialislarvae (EC50: 3.53-28.60 mu M) and low toxicity to this macrofouling species (LC50> 500 mu M and LC50/EC50: 17.42-141.64), and two of them (7and10) showed no general marine ecotoxicity (Artemia salinamortality) after 48 h of exposure. Regarding the mechanism of action in mussel larvae, the best performance compounds4and5might be acting by the inhibition of acetylcholinesterase activity (in vitro and in silico studies), while7and10showed specific targets (proteomic studies) directly related with the mussel adhesive structure (byssal threads), given by the alterations in the expression ofMytiluscollagen proteins (PreCols) and proximal thread proteins (TMPs). A quantitative structure-activity relationship (QSAR) model was built with predictive capacity to enable speeding the design of new potential active compounds.
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| 3. |
- Campos, Joana, et al.
(författare)
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Fed-batch strategies for biodetoxification in production of optically pure lactic acid from softwood hydrolysate using Pediococcus acidilactici
- 2023
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Ingår i: Process Biochemistry. - : Elsevier BV. - 1359-5113. ; 125, s. 162-170
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Tidskriftsartikel (refereegranskat)abstract
- Optically pure lactic acid (LA) is important for the development of specialized applications for poly-lactic acid (PLA). To pursue sustainable production, feedstocks such as lignocellulosic biomass need to be investigated. The present study focused on the production of L-LA from softwood hydrolysate with Pediococcus acidilactici TY112. One of the challenges when using this substrate is the presence of inhibitors, such as furfural and 5-hydroxymethylfurfural (HMF), formed during pretreatment. To investigate adaptation, fed-batch experiments on softwood hydrolysate and model media were conducted. Although LA production was still affected by the presence of other inhibitors in the hydrolysate, P. acidilactici TY112 was capable of converting HMF and furfural and partly detoxify both hydrolysate and synthetic media. The strain adapted to the inhibitors present, if fed at a low rate (30 mL·h−1 for model medium with inhibitors and 15 mL·h−1 for softwood hydrolysate, both with 30 g·L−1 glucose and 45 g·L−1 mannose). Regarding carbon source consumption, a feeding rate of 30 mL·h−1 limited the uptake of glucose, leading to improved mannose uptake, with LA yields higher than 0.86 g·g−1. This study shows the potential of P. acidilactici TY112 for the production of L-LA from softwood hydrolysate which is regarded as inhibitory.
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| 4. |
- Campos, Joana, et al.
(författare)
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Optically pure lactic acid production from softwood-derived mannose by Pediococcus acidilactici
- 2021
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656. ; 335, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Softwood is of interest as a renewable carbon source for production of lactic acid. Softwood hydrolysate contains a high content of mannose. Lactic acid production from mannose by two modified strains, L-lactic acid producing Pediococcus acidilactici TY112 and D-lactic acid producing ZP26, was investigated in the current work. The two strains efficiently converted mannose to L- and D-lactate isomers with an optical purity exceeding 99 %, although the mannose utilization rates were lower than the glucose utilization rates. The mannose conversion to L- and D-lactic acids by P. acidilactici was also confirmed in dilute spruce hemicellulose hydrolysate. The present study provides important knowledge on utilization of the spectrum of fermentable sugars in softwood for future production of chiral lactic acid from lignocellulose feedstocks.
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| 5. |
- Campos, Joana, et al.
(författare)
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Overcoming extended lag phase on optically pure lactic acid production from pretreated softwood solids
- 2023
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Ingår i: Frontiers in Bioengineering and Biotechnology. - 2296-4185. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Optically pure lactic acid (LA) is needed in PLA (poly-lactic acid) production to build a crystalline structure with a higher melting point of the biopolymer than that of the racemic mixture. Lignocellulosic biomass can be used as raw material for LA production, in a non-food biorefinery concept. In the present study, genetically engineered P. acidilactici ZP26 was cultivated in a simultaneous saccharification and fermentation (SSF) process using steam pretreated softwood solids as a carbon source to produce optically pure D-LA. Given the low concentrations of identifiable inhibitory compounds from sugar and lignin degradation, the fermentation rate was expected to follow the rate of enzymatic hydrolysis. However, added pretreated solids (7% on weight (w/w) of water-insoluble solids [WIS]) significantly and immediately affected the process performance, which resulted in a long lag phase (more than 40 h) before the onset of the exponential phase of the fermentation. This unexpected delay was also observed without the addition of enzymes in the SSF and in a model fermentation with glucose and pretreated solids without added enzymes. Experiments showed that it was possible to overcome the extended lag phase in the presence of pretreated softwood solids by allowing the microorganism to initiate its exponential phase in synthetic medium, and subsequently adding the softwood solids and enzymatic blend to proceed to an SSF with D-LA production.
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| 6. |
- Campos, Joana, et al.
(författare)
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Waste Viscose for Optically pure Lactic acid Production
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Ingår i: Waste and Biomass Valorization. - 1877-2641.
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Tidskriftsartikel (refereegranskat)abstract
- Recycling of textile fibers is a mandatory step in the life-cycle of fabrics to avoid incineration or landfilling. After fiber-to-fiber recycling, cellulose fiber saccharification opens the door to the production of biochemical building blocks through microbial fermentation. This study documents for the first time the production of optically pure D-lactic acid (D-LA), one of the precursors of polylactic acid (PLA), from post-consumer waste viscose. Enzymatic hydrolysis was applied to white and colored waste viscose to produce two glucose-rich solutions that were used as carbon source for the genetically modified Pediococcus acidilactici ZP26. Afterward, batch and fed-batch cultivations were conducted with very similar results for the control and both waste viscose hydrolysates (white and colored). The strain was able to produce D-LA without any signs of inhibition by possibly toxic compounds present in the recycled textiles (additives, dyes, and other contaminants). The highest D-LA concentration and yield was reached in the batch reactors with colored waste viscose at 42.4 g/L and 0.97 g/g, respectively. In the fed-batch cultivations, the best result was achieved with the white waste solution, with 59.5 g of D-LA (40.8 g/L), and a yield on total glucose of 0.70 g/g. Notwithstanding the need for more research in the utilization of saccharified waste viscose as carbon source for bioprocesses, this is an important proof of concept of an application of streams from tertiary recycling of cellulosic fibers in the production of platform biochemicals. Graphical Abstract: (Figure presented.)
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| 7. |
- Coutinho Campos, Joana
(författare)
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Optically pure lactic acid production from lignocellulosic biomass
- 2023. - 1
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lactic acid is a platform chemical that can be used for many applications. More recently, optically pure lactic acid—L- or D-lactic acid enantiomers—have been used for the polymerisation to poly-lactic acid (PLA). The possibility of tailoring the properties of this bioplastic by adjusting the ratio of each enantiomer might help to accelerate the substitution of petroleum-based plastics with bio-based and compostable alternatives. Today, PLA is produced primarily from raw materials that can be used as food—sugarcane and corn. To decrease the utilisation of food crops for producing bioplastics, alternative processes usinglignocellulosic biomass and organic waste are under development. In this thesis, optically pure lactic acid production from lignocellulosic biomass was examined using softwood (spruce) and post-consumer waste viscose.Softwood was subjected to a SO2-catalysed steam explosion pretreatment to saccharify hemicellulose and open the solid structure of cellulose and lignin. The pretreated softwood was separated into two fractions (liquid and solid). The hemicellulose hydrolysate (liquid fraction) was used without further treatment as a carbon source in the bacterial cultivations, whereas the solid fraction of pretreated softwood and the waste viscose (a man-made cellulosic fibre) had to undergo enzymatic hydrolysis before use in cultivation studies.Two strains of Pediococcus acidilactici were used in this work. Each strain was genetically modified to produce only one enantiomer: P. acidilactici TY112 generates L-lactic acid, and P. acidilactici ZP26 produces D-lactic acid. The two strains were used to produce the respective enantiomers from the liquid fraction of softwood, with similar results. Subsequently, their resistance to the inhibitory compounds generated during the pretreatment was evaluated. A fed-batch strategy for co-consumption of glucose and mannose and conversion of hydroxymethylfurfural (HMF) and furfural was studied and reported. Simultaneous saccharification and fermentation (SSF) was used in cultivations with the softwood solid fraction as the carbon source. Despite initial results of a long lag phase of 48 h under several conditions, this adaptation phase was decreased by starting the cultivation with monomeric sugars before the addition of the solid fraction and enzymatic blend for SSF. P. acidilactici ZP26 also showed promising results in cultivations using saccharified waste viscose, despite the presence of dyes and likely other additives and contaminants in the media.These results add knowledge to a broader research project that aims to use P. acidilactici to produce optically pure lactic acid and high-quality PLA from several sources of lignocellulosic biomass. These modified bacteria synthesise their respective enantiomers with high yields, even in the presence of possibly toxic compounds in softwood and waste viscose.
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| 8. |
- Kardeby, Caroline, et al.
(författare)
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Heparin and heparin proteoglycan-mimetics activate platelets via PEAR1 and PI3K beta
- 2023
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier. - 1538-7933 .- 1538-7836. ; 21:1, s. 101-116
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Tidskriftsartikel (refereegranskat)abstract
- Background: Platelet endothelial aggregation receptor 1 (PEAR1) is a singletransmembrane orphan receptor primarily expressed on platelets and endothelial cells. Genetic variants of PEAR1 have repeatedly and independently been identified to be associated with cardiovascular diseases, including coronary artery disease.Objectives: We have identified sulfated fucoidans and their mimetics as ligands for PEAR1 and proposed that its endogenous ligand is a sulfated proteoglycan. The aim of this study was to test this hypothesis.Methods: A heparin proteoglycan-mimetic (HPGM) was created by linking unfractionated heparin (UFH) to albumin. The ability of the HPGM, UFH and selectively desulfated heparins to stimulate platelet aggregation and protein phosphorylation was investigated. Nanobodies against the 12th to 13th epidermal growth factor-like repeat of PEAR1 and phosphoinositide 3-kinase (PI3K) isoform-selective inhibitors were tested for the inhibition of platelet activation.Results: We show that HPGM, heparin conjugated to an albumin protein core, stimulates aggregation and phosphorylation of PEAR1 in washed platelets. Platelet aggregation was abolished by an anti-PEAR1 nanobody, Nb138. UFH stimulated platelet aggregation in washed platelets, but desulfated UFH did not. Furthermore, HPGM, but not UFH, stimulated maximal aggregation in platelet-rich plasma. However, both HPGM and UFH increased integrin alpha IIb(33 activation in whole blood. By using PI3K isoform-selective inhibitors, we show that PEAR1 activates PI3K(3, leading to Akt phosphorylation.Conclusion: Our findings reveal that PEAR1 is a receptor for heparin and HPGM and that PI3K(3 is a key signaling molecule downstream of PEAR1 in platelets. These findings may have important implications for our understanding of the role of PEAR1 in cardiovascular disease.
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| 9. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 10. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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