Leveraging genomic risk factors for major depressive disorder to provide mechanistic insights and predictive neurobiological markers

Major Depressive Disorder (MDD) is a disabling, common psychiatric disorder and the leading cause of global disability. A complex combination of genetic and environmental factors gives rise to MDD, although the exact aetiology has not been identified. Genome-wide association studies (GWAS) have established that MDD has a moderate heritability of approximately 37%. MDD has in the past also been associated with abnormalities of white matter microstructure, which represents the brain’s connectivity network. This network is also moderately heritable, providing rationale to investigate its relationship to MDD genetic risk. Over recent years, there has been considerable progress in establishing genetic contributions to MDD. These advances can be harnessed, in combination with neuroimaging and epigenomics, to understand the neurobiology of the disorder. This has only recently become possible at sufficient scale with the availability of large publicly available datasets including genomic, epigenomic, and neuroimaging data. In the current thesis, I therefore aimed to leverage genetic, epigenetic, and neuroimaging data in two large datasets, UK Biobank (N range: 6,400 – 14,800) and Generation Scotland: Scottish Family Health Study (N = 625). Specifically, I aimed to uncover links between white matter microstructure, as measured by fractional anisotropy and mean diffusivity, and (i) differential gene expression as indexed by expression quantitative trait loci (eQTLs) scores in chapter 2; here, decreased white matter integrity was found to be associated with 6 scores regulating genes previously reported to be implicated in neurological and neuropsychiatric disorders, while 2 scores regulating neurodevelopment-linked genes were associated with increased white matter integrity; (ii) MDD genetic risk stratified by the NETRIN1 Signalling Pathway, previously implicated in MDD, indexed by polygenic risk scores (PRS) in chapter 3; results indicated novel associations between the pathway-focussed PRS and decreased white matter integrity in thalamic radiations, as well as several association fibres, including superior and inferior longitudinal fasciculus; (iii) a novel wholegenome epigenetic risk score for MDD, which uncovered an association with MDD, but no significant associations with changes in white matter microstructure (chapter 4). The overall aim of the thesis was to use advanced genomic techniques to stratify genetic function and risk and explore epigenetic risk for MDD in order to identify novel links to structural brain connectivity. Overall, the three studies provide a strong rationale for integrating neuroimaging, genomic and epigenomic data. Specifically, findings in chapter 2 indicate the importance of DCAKD, SLC35A4, SEC14L4, SRA1, PLEKHM1, UBE3C, NMT1, and CPNE1, not previously found by conventional GWAS approaches. This suggests that integrating neuroimaging and genetic expression data may uncover novel associations that inform disease- or trait-specific genetic links to brain connectivity. Chapter 3 results provide a rationale for investigating the NETRIN1 Signalling Pathway and emphasise the role of thalamic connections in MDD within this biological pathway, indicating that novel associations with brain connectivity may be uncovered at a more focused level when stratifying MDD risk by biology. Finally, results from chapter 4 indicate that epigenetics play an important role in MDD risk, although further analysis including larger-scale epigenetic and neuroimaging data should be carried out to uncover the role of epigenetics in relation to brain phenotypes

Morphological Research on Indigenous Sambucus Species Pollen

The pollen grains have a definite shape, size, colour, structure for each species, genus and family and these characters are useful for systematical botany. The pollen has nutritive properties due to its content: proteins, lipids, carbohydrates, vitamins, hormones and minerals. In the Romanian flora vegetate three species of Sambucus, but only S. nigra L. (elder or black elder) supplies a vegetal medical product, Sambuci flos or elder flowers, whereas the others species S. ebulus L. (dwarf elder) and S. racemosa L. (mountain elder or red elder) are considered adulterations. The pollen of Sambucus species were already studied using optical microscopy (Tarnavschi et al.), but the images are in one single layout, therefore the structure details cannot be easily notice. In this context the pollen grains of the three species already mentioned above were studied by SEM (Scanning Electron Microscopy). The results demonstrated that this pollen have a small-middle size, oblat-sphaeroidal-prolat shape, threecolpat and the exine adornments are of reticulate type, haemitectate with sticks in the meshs of polygonale net. The flavonoids content is lower than in others species (0.146-0.564 %). The SEM analyse of Sambucus pollen allow a reliable identification of the genus but less for the species

Considerations on Applying Practical Control Methods in the Biological Treatment of Wastewaters from Paper Manufacturing

Due to high efficiency, in terms of effluent quality, the activated sludge treatment is the most common method for removing the biodegradable impurities from industrial and urban wastewaters. Although these engineering systems of biological wastewater treatments increase the rate of biodegradable substances removing, in most cases, these are rarely able to achieve the maximum performances due to the lack of some fast methods to monitor and control the living biomass. In this context, in present paper are described some methods for evaluation of viability and biological activity of activated sludge, as essential parameters for ensuring the performance of biological treatment process. The proposed methods are based on the determination of metabolically active bacteria in activated sludge, using the activity of dehydrogenase enzymes (Triphenyl tetrazolium chloride TTC method) in the biological treatment of wastewaters generated from the paper manufacturing process

Ekspresja adiponektyny w otyłości trzewnej jest istotnym wyznacznikiem insulinooporności w otyłości olbrzymiej

Introduction: Visceral adiposity is associated with decreased serum adiponectin levels, peripheral resistance to insulin and an increased risk of cardio-metabolic complications. However, the link between adiponectin expression in visceral adipose tissue (VAT), its serum levels and metabolic protection is controversial. The aim of this study was to investigate the relationship between the adiponectin gene expression in VAT and clinical and metabolic parameters in patients with severe obesity. Material and Methods: This is a cross-sectional study that included 51 severely obese patients (age 43.24±11.29 years, BMI 45.13±8.67 kg/m2), extensively evaluated clinically and biologically (metabolic tests, serum adiponectin measurements, HOMA-IR) before bariatric surgery. Omental adipose tissue was sampled during the intervention and the relative quantification of adiponectin gene expression was performed by real-time PCR, using beta-actin as reference gene. Results. Adiponectin mRNA in VAT was significantly higher in obese insulin-sensitive patients than in the rest of obese patients (p < 0.05) and negatively correlated with HOMA-IR (r =-0.354, p=0.016) and uric acid (r =-0.304, p=0.045). After adjustment for gender, TG/HDL ratio and uric acid, adiponectin expresion (β= -0.439, p=0.001), waist circumference (β=0.467, p=0.001) and serum adiponectin (β =-0.339, p=0.011) remained significantly associated with HOMA-IR, together explaining more than 50% of its variation. Conclusions. In severely obese patients, adiponectin gene expression in VAT is negatively correlated with serum levels of uric acid and is an independent determinant, together with anthropometric parameters of visceral obesity and serum adiponectin levels, of insulin resistance.Wstęp: Otyłość trzewna związana jest ze zmniejszonym stężeniem adiponektyny w surowicy krwi, obwodową opornością na działanie insuliny oraz ze zwiększonym ryzykiem powikłań sercowo-metabolicznych. Jednak związek między ekspresją adiponektyny w trzewnej tkance tłuszczowej, jej stężeniem w surowicy krwi a ochroną metaboliczną jest kwestią sporną. Celem niniejszej pracy było zbadanie związku między ekspresją genu adiponektyny w trzewnej tkance tłuszczowej a klinicznymi i metabolicznymi parametrami pacjentów ze znaczną otyłością. Materiał i metody: To przekrojowe badanie obejmowało 51 znacznie otyłych pacjentów (wiek 43,24 ± 11,29 roku, BMI 45,13 ± 8,67 kg/m2), szczegółowo ocenionych pod względem klinicznym i biologicznym (testy metaboliczne, pomiary stężenia adiponektyny w surowicy krwi, wskaźnik HOMA-IR) przed operacją bariatryczną. Podczas operacji pobrano tkankę tłuszczową sieci. Względna ocena ilościowa ekspresji genu adiponektyny była przeprowadzona metodą PCR w czasie rzeczywistym. Wyniki: Poziom mRNA adiponektyny w trzewnej tkance tłuszczowej był znacząco wyższy u otyłych pacjentów wrażliwych na insulinę niż u pozostałych otyłych pacjentów (p &lt; 0,05) oraz ujemnie skorelowany ze wskaźnikiem HOMA-IR (r = –0,354, p = 0,016) i kwasem moczowym (r = –0,304, p = 0.045). Po uwzględnieniu płci, wskaźnika TG/HDL i kwasu moczowego, ekspresja adiponektyny (β = –0,439, p = 0,001), obwód talii (β = 0,467, p = 0,001) i poziom adiponektyny w surowicy krwi (β = –0,339, p = 0,011) pozostały istotnie związane ze wskaźnikiem HOMA-IR, łącznie wyjaśniając ponad 50% jego wariancji. Wnioski: W przypadku znacznie otyłych pacjentów ekspresja genu adiponektyny w trzewnej tkance tłuszczowej jest ujemnie skorelowana ze stężeniem kwasu moczowego w surowicy krwi i razem z antropometrycznymi parametrami otyłości trzewnej oraz stężeniem adiponektyny w surowicy krwi jest niezależnym wyznacznikiem insulinooporności

Epigenome-wide association study of global cortical volumes in Generation Scotland:Scottish Family Health Study

Funding This work was supported by the Wellcome Trust [104036/Z/14/Z]. Acknowledgements Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z). MCB is supported by a Guarantors of Brain Non-clinical Post-Doctoral Fellowship. AMM is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z) and UKRI MRC (MC_PC_17209, MR/S035818/1). KLE is supported by the NARSAD Independent Investigator Award (Grant ID: 21956). JMW is supported by UK Dementia Research Institute which is funded by the MRC, Alzheimer’s Research UK and Alzheimer’s Society, by the Fondation Leducq (16 CVD 05), and the Row Fogo Centre for Research Into Ageing and the Brain (BRO- D.FID3668413). This work is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 847776.Peer reviewedPublisher PD

Towards a circular economy in the aviation sector using eco-composites for interior and secondary structures. Results and recommendations from the EU/China project ECO-COMPASS

Fiber reinforced polymers play a crucial role as enablers of lightweight and high performing structures to increase efficiency in aviation. However, the ever-increasing awareness for the environmental impacts has led to a growing interest in bio-based and recycled ‘eco-composites’ as substitutes for the conventional synthetic con-stituents. Recently, the international collaboration of Chinese and European partners in the ECO-COMPASS pro-ject provided an assessment of different eco-materials and technologies for their potential application in aircraft interior and secondary composite structures. This project summary reports the main findings of the ECO-COM-PASS project and gives an outlook to the next steps necessary for introducing eco-composites as an alternative solution to fulfill the CLEAN SKY target