| 1. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 2. |
- Lundberg, Anna, et al.
(författare)
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Expression of toll-like receptors and immune-regulatory markers during early infancy and allergy development in Estonian and Swedish infants
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Allergies have increased during the last decades with the highest prevalences in countries with a Westernised lifestyle. As microbial activation might be required for an accurate maturation of the immune system, a reduced or altered microbial exposure during infancy has been suggested as a possible cause for the increase of allergic diseases in affluent countries. Aim: The aim of this study was to investigate the gene expression of TLR2, TLR4, Foxp3, Ebi3 and SOCS3 involved in LPS signaling pathways and immune regulation in two prospectively followed birth cohorts, one from Estonia and one from Sweden, in relation to domestic endotoxin levels and allergy development. Material and methods: Twenty-three children from Estonia and 52 from Sweden were followed from birth to five years of age regarding allergy development using questionnaires, clinical examinations and skin prick tests. RNA was isolated from unstimulated peripheral blood mononuclear cells (PBMC) in samples collected at birth, 3, 6, 12 and 24 months of age. mRNA expression of TLR2, TLR4, SOCS3, Ebi3 and Foxp3 was analysed with real-time RTPCR. The mRNA expression of the genes were compared to previously obtained data of LPS/IFN-γ induced cytokine and chemokine PBMC secretion at the corresponding time-points and also to domestic endotoxin levels. Results: The Estonian infants had higher mRNA expression of the two regulatory T cell (Treg) associated markers Foxp3 and Ebi3 at birth than the Swedish infants. The Foxp3 and Ebi3 expression correlated at all time-points. The mRNA expression of TLR2, TLR4 and SOCS3 was similar in Estonian and Swedish infants at all ages. None of the genes were associated with endotoxin levels.TLR4 mRNA expression correlated positively with cytokines that were upregulated by LPS/IFN- γ stimulation, but was negatively correlated to CCL2 secretion which was downregulated by the stimulation. Low expression of TLR2 mRNA at birth was found in Swedish children who were allergic at 5 years of age. Sensitisation up to 5 years of age was associated with low Ebi3 expression at birth. Conclusion: Estonian children are born with enhanced Ebi3 and Foxp3 expression compared to Swedish children, suggesting an increased capacity for early immune regulation among infants from a country with a low prevalence of allergic disease. An increased early capacity to respond to TLR2 ligands, i.e. Gram positive bacteria, may protect against allergy development.
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| 3. |
- Rudjito, Reskandi C., et al.
(författare)
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Comparison of xylanases from different glycosyl hydrolase familiesfor the production of arabinoxylan-oligosaccharides with prebioticpotential
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this study, we compared the activity of four different xylanases (GH 5_34, 8, 10 and 11) for the production of arabinoxylan-oligosaccharide or (A)XOS from cereal arabinoxylans as potential prebiotics. In terms of efficiency, the AcXyn10A and TlXyn11 produced larger quantities of small (A)XOS of mainly X1-X3 in a shorter period of time. The BXyn8 was most restricted by high arabinose substitution but could still accommodate them at the +2 subsite. The GpXyn5_34 preferred high arabinose substitution, requiring an arabinose at the -1 subsite for cleavage. Both the BXyn8 and GpXyn5_34 produced longer (A)XOS that were mostly linear and substituted, respectively. During fermentation of (A)XOS on selected gut bacteria, the long-substituted products of GpXyn5_34 stunted the growth of B. ovatus and B. adolescentis, while the mid-length, linear products of BXyn8 favoured the growth of both bacteria.
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| 4. |
- Rudjito, Reskandi C., et al.
(författare)
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Enzyme-assisted recovery of recalcitrant feruloylated arabinoxylans in combination with subcritical water extraction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Wheat bran (Wb) is an abundant and low valued feedstock that can be valorised for its high arabinoxylan (AX) content by means of sustainable bioprocessing. However, its recalcitrant nature in terms of molecular structure and supramolecular interactions hinders its efficient fractionation. In this study we have developed an integrated bioprocess combining consecutive rounds of subcritical water extraction (SWE) and enzymatic treatments (ET) for maximised recovery of feruloylated AXs and oligosaccharides from Wb. After the first round of SWE (SWE I), enrichment of AX was observed with increased extraction time, along with an increased complexity of the AX structure in terms of A/X ratio and ferulic acid (FA) content. The residual wheat bran (Wb-R) after SWE I was subjected to ET using two different enzymatic cocktails that were sequentially screened on Wb-R. The enzymatic cocktails contained each a feruloyl esterase (F) and a xylanase (X) from either the glycosyl hydrolase family GH10 (X10A) or GH5_21 (X5_21) respectively, with distinct activity and substrate selectivity onto complex AX. The combination of the GH10 xylanase and feruloyl esterase resulted in higher hydrolysate yields composed of mainly xylobiose (X2) and monomeric FA, while the hydrolysate from the GH5_21 xylanase and feruloyl esterase was composed of longer substituted oligo- and polysaccharides. The residues after enzymatic treatments were then subjected to a second round of SWE (SWE II). Comparatively, the SWE II extract after GH10 xylanase and feruloyl esterase treatment resulted in higher yields than the GH5_21 xylanase treatment, and the isolated AX was highly substituted (A/X: 0.7) and exhibited a high molar mass distribution (104 Da). The incorporation of selective xylanolytic enzymes in the integrated SWE bioprocess resulted in increased AX yields and produced AX with tailored molecular structure in terms of degree of substitution, molar mass, and ferulic acid content, which can potentially be used as matrices for advanced biomedical and nutritional applications.
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| 5. |
- Rudjito, Reskandi C., et al.
(författare)
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Regioselectivity and patterns of arabinose substitution and feruloylation determine the activity of xylanases from GH5
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Endo-1,4-β-xylanases from glycosyl hydrolase family 5 (GH5) prefer highly substituted arabinoxylans (AX) due to the need of arabinose decorations as a specificity determinant for cleavage. In this study, we compared the activity of GH5 xylanases from subfamilies GH5_21, GH5_34 and GH5_35, in terms of how arabinose substitutions and feruloylation are tolerated by the enzymes. We specifically prepared three AX substrates from wheat and barley bran with distinct arabinose substitution patterns and ferulic acid content. The GH5_34 xylanase was the most active in all substrates, followed by the GH5_21 and GH5_35. The regioselectivity and patterns of arabinose substitution were more important than the overall degree of arabinose substitution of the AX substrates. All the GH5 xylanases targeted C(O)-3 linked arabinose substitutions, producing oligosaccharides with a C(O)-3 linked arabinose at the reducing end. Ferulic acid (FA) slightly hindered enzymatic activity, as it obstructed the C(O)-3 linked arabinose in becoming a specificity determinant for cleavage. This study highlights the exquisitely specific nature of GH5 β-xylanases, opening new avenues for their application in tackling highly substituted recalcitrant AX substrates and for molecular tailoring of polysaccharides.
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| 6. |
- Yalamanchili, Kumar, et al.
(författare)
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Growth and Mechanical Behavior of Nanoscale Structures in ZrN/Zr0.63Al0.37N Multilayers
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Structure and mechanical properties of monolithic and nanoscale multilayers of ZrN/Zr0.63Al0.37N are investigated as a function of Zr0.63Al0.37N layer thickness. ZrN/Zr0.63Al0.37N multilayers were deposited by reactive magnetron sputtering on MgO (001) substrates at a temperature of 700 °C. Monolithic Zr0.63Al0.37N film shows a chemically segregated nanostructure of cubic-ZrN and wurtzite-AlN rich domains with incoherent interfaces. Three dimensional atom probe measurements reveal comparable chemical segregation between monolithic and multilayer Zr0.63Al0.37N film. The multilayers show systematic changes in nanostructure as a function of Zr0.63Al0.37N layer thickness resulting in mechanical properties such as hardness and fracture resistance being tunable. A maximum hardness of 34 GPa is achieved with 10 nm Zr0.63Al0.37N layer thickness having semi-coherent interfaces between wurtzite-AlN and cubic-ZrN rich domains. Higher fracture resistance is achieved at 2nm Zr0.63Al0.37N where AlN rich domains are epitaxially stabilized in the metastable cubic phase.
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