Puun lahoamisprosessin seuraaminen NMR- ja MRI-menetelmillä

Tutkielma käsittelee NMR-spektroskopian ja magneettikuvauksen menetelmiä, joilla lahoavaa puuta voidaan mahdollisesti kuvata ja tutkia. Lisäksi tutkielmassa esitetään tärkeimpiä teoreettisia lähtökohtia puun lahoamiselle, NMR-spektroskopialle sekä magneettikuvaukselle

Characterization of the decay process of Scots pine caused by Coniophora puteana using NMR and MRI

Abstract Wood decay is an economically significant process, as it is one of the major causes of wood deterioration in buildings. In this study, the decay process of Scots pine (Pinus sylvestris) samples caused by cellar fungus (Coniophora puteana) was followed by nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) methods. Altogether, 30 wood sample pieces were exposed to fungus for 10 weeks. Based on the decrease of the dry mass, the samples were categorized into three classes: decomposed (mass decrease 50–70%), slightly decomposed (10–50%), and nondecomposed (<10%). MRI made it possible to identify the active regions of fungus inside the wood samples based on the signal of free water brought by the fungus and arisen from the decomposition of wood carbohydrates. MRI implies that free water is not only created by the decay process, but fungal hyphae also transports a significant amount of water into the sample. Two-dimensional ¹H T₁-T₂ relaxation correlation NMR measurements provided detailed information about the changes in the microstructure of wood due to fungal decomposition. Overall, this study paves the way for noninvasive NMR and MRI detection of fungal decay at early stages as well as the related structural changes

Molecular mechanisms of synaptotoxicity and neuroinflammation in Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder, which is clinically associated with a global cognitive decline and progressive loss of memory and reasoning. According to the prevailing amyloid cascade hypothesis of AD, increased soluble amyloid-β (Aβ) oligomer levels impair the synaptic functions and augment calcium dyshomeostasis, neuroinflammation, oxidative stress as well as the formation of neurofibrillary tangles at specific brain regions. Emerging new findings related to synaptic dysfunction and initial steps of neuroinflammation in AD have been able to delineate the underlying molecular mechanisms, thus reinforcing the development of new treatment strategies and biomarkers for AD beyond the conventional Aβ- and tau-targeted approaches. Particularly, the identification and further characterization of disease-associated microglia and their RNA signatures, AD-associated novel risk genes, neurotoxic astrocytes, and in the involvement of complement-dependent pathway in synaptic pruning and loss in AD have set the outstanding basis for further preclinical and clinical studies. Here, we discuss the recent development and the key findings related to the novel molecular mechanisms and targets underlying the synaptotoxicity and neuroinflammation in AD

Effect of process variables on the solvolysis depolymerization of pine kraft lignin

Abstract Lignin modification opens the possibility of using it in polyol bio-based polymers, such as phenol–formaldehyde resins, polyurethanes, composites, and binders. Pine kraft lignin Indulin AT was partially depolymerized and the resulting products analyzed to determine their degree of valorization. Depolymerized lignin products were analyzed by GPC-SEC (molar mass), ∆ε-IDUS (phenolic hydroxyls), HACL (formaldehyde uptake), 13C-NMR (hydroxyl and methoxyl groups), and 1H-DOSY (molar mass distribution). The dominant parameter in lignin depolymerization by solvolysis was reaction temperature. According to the results, a higher reaction temperature decreases the average molar masses and PDI of lignin as well as the primary and secondary aliphatic hydroxyls, while simultaneously increasing the phenolic hydroxyls and formaldehyde uptake of lignin. Other variables (time, formic acid wt %, ethanol wt %, lignin load) had lesser effects. Partial depolymerization by solvolysis in mild conditions without catalyst is a viable valorization route for lignin, by which lignin properties can be significantly improved

Comparison of lignin fractions isolated from wheat straw using alkaline and acidic deep eutectic solvents

Abstract This study aims to examine the characteristics of two solid lignin fractions isolated from wheat straw using alkaline and acidic deep eutectic solvents (DESs). The chemical properties and morphological characteristics of the two lignin fractions were evaluated by measuring their purity, elemental composition, molecular weight and particle size distributions, and microstructure. Their chemical structure was evaluated using DRIFT (diffuse reflectance infrared Fourier transform) spectroscopy, GPC (gel permeation chromatography), TGA (thermogravimetric analysis), ¹³C NMR (nuclear magnetic resonance), ³¹P NMR, and HSQC NMR. Our findings showed that the lignin isolated using alkaline DESs was less pure and had a smaller particle size, higher molecular weight, and thermal stability compared to the lignin isolated using acidic DESs. Their lignin structure was also determined to be different due to varying selective fractures on the linkages of lignin. These results suggest that the DES treatments could selectively extract lignin from wheat straw with different yields, compositions, morphologies, and structures, which could then provide a theoretical basis for the selection of DESs for specially appointed lignin extraction

Diabetes is associated with familial idiopathic normal pressure hydrocephalus:a case–control comparison with family members

Abstract Background: The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods: Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher’s exact test (two-tailed), the Mann–Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results: Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1–12.9, p = 0.030). Conclusions: Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Abstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids

FinnGen provides genetic insights from a well-phenotyped isolated population.

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10-11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants