Molecular patterns behind immunological and metabolic alterations in lysinuric protein intolerance

Lysinuric protein intolerance (LPI) is a recessively inherited disorder characterised by reduced plasma and increased urinary levels of cationic amino acids (CAAs), protein malnutrition, growth failure and hyperlipidemia. Some patients develop severe immunological, renal and pulmonary complications. All Finnish patients share the same LPIFin mutation in the SLC7A7 gene that encodes CAA transporter y+LAT1. The aim of this study was to examine molecular factors contributing to the various symptoms, systemic metabolic and lipid profiles, and innate immune responses in LPI. The transcriptomes, metabolomes and lipidomes were analysed in whole-blood cells and plasma using RNA microarrays and gas or liquid chromatography-mass spectrometry techniques, respectively. Toll-like receptor (TLR) signalling in monocyte-derived macrophages exposed to pathogens was scrutinised using qRT-PCR and the Luminex technology. Altered levels of transcripts participating in amino acid transport, immune responses, apoptosis and pathways of hepatic and renal metabolism were identified in the LPI whole-blood cells. The patients had increased non-essential amino acid, triacylglycerol and fatty acid levels, and decreased plasma levels of phosphatidylcholines and practically all essential amino acids. In addition, elevated plasma levels of eight metabolites, long-chain triacylglycerols, two chemoattractant chemokines and nitric oxide correlated with the reduced glomerular function in the patients with kidney disease. Accordingly, it can be hypothesised that the patients have increased autophagy, inflammation, oxidative stress and apoptosis, leading to hepatic steatosis, uremic toxicity and altered intestinal microbe metabolism. Furthermore, the LPI macrophages showed disruption in the TLR2/1, TLR4 and TLR9 pathways, suggesting innate immune dysfunctions with an excessive response to bacterial infections but a deficient viral DNA response.

Static waves in corporate space : characterizing oscillating trading patterns in New York stock exchange

Various researches in the field of econophysics has shown that fluid flow have analogous phenomena in financial market behavior, the typical parallelism being delivered between energy in fluids and information on markets. However, the geometry of the manifold on which market dynamics act out their dynamics (corporate space) is not yet known. In this thesis, utilizing a Seven year time series of prices of stocks used to compute S&P500 index on the New York Stock Exchange, we have created local chart to the corporate space with the goal of finding standing waves and other soliton like patterns in the behavior of stock price deviations from the S&P500 index. By first calculating the correlation matrix of normalized stock price deviations from the S&P500 index, we have performed a local singular value decomposition over a set of four different time windows as guides to the nature of patterns that may emerge. I turns out that in almost all cases, each singular vector is essentially determined by relatively small set of companies with big positive or negative weights on that singular vector. Over particular time windows, sometimes these weights are strongly correlated with at least one industrial sector and certain sectors are more prone to fast dynamics whereas others have longer standing waves.

Diel patterns and tissue-specificity of environmental responses in fish

Humans are profoundly changing aquatic environments through climate change and the release of nutrients and chemicals. To understand the effects of these changes on natural populations, knowledge on individuals��� environmental responses is needed. At the molecular level, the environmental responses are partly mediated by chances in messenger RNA and protein levels. In this thesis I study messenger RNA and protein responses to an assortment of environmental stressors in fish. As daily (diel) rhythms are known to be ubiquitous in different tissues, I particularly focus on diel patterns in the responses. The studied species are the three-spined stickleback (Gasterosteus aculeatus L.) and the Arctic char (Salvelinus alpinus L.), both of which have circumpolar distribution in the Northern hemisphere. In the first two studies, three-spined sticklebacks were exposed to both the non-steroidal anti-inflammatory drug diclofenac and low-oxygen conditions (hypoxia), and their responses measured at separate time points in the liver and gills. The results show how the seemingly unrelated environmental stressors, hypoxia and anti-inflammatory drugs, can have harmful combined effects that differ from the effects of each stressor alone. Moreover, both stressors disturbed natural diel patterns in gene expression. In the third study, I studied the responses of three-spined sticklebacks to two test chemicals: one used in hormonal medicine (17��-ethinyl-oestradiol) and one used as a plasticizer and solvent chemical (di-n-butyl phthalate). The results suggest that the phthalate can affect genes related to spermatogenesis in fish testes, while estrogen-mimicking compounds can lead to numerous disturbances in the endocrine system. In the final study, the temperature-dependence of diel rhythms in messenger RNA levels were evaluated in the liver tissue of the Arctic char, a cold-adapted salmonid. The results show that cold acclimation repressed diel rhythms in gene expression compared to warm-acclimated fish, in which the expression of hundreds of genes was rhythmic, suggesting the circadian clock of the Arctic fish species can be sensitive to temperature. Overall, the results of the thesis indicate that fishes��� responses to abiotic factors interact with their diel rhythms, and more studies on the consequences of these interactions are needed to comprehensively understand human impacts on ecosystems.

Travel changes thought and men : a fresh perspective on the travels of a literary icon

Kirjallisuusarvostelu

Expressing the self in postmodern travel consumption: a case study of students

The study approaches student travel from the perspective of postmodern consumption. The background is in the observation that the student travel market has a vast potential, but it is not necessarily capitalized upon to the extent it could. This might partly have to do with the peculiarities of postmodernity: consumption is characterized by unpredictability and abstract motives. The research questions are built around what constitutes student travel consumption and how can students be categorized according to motivation, behaviour and values. Also identity and expressiveness are present and it is evaluated, if travel services facilitate these background is the observation that the student travel market has a vast potential, but it is not necessarily capitalized upon to the extent it could be. This might partly have to do with the peculiarities of postmodernity: consumption is characterized by unpredictability and abstract motives. The research questions are built around what constitutes student travel consumption and how can students be categorized according to motivation, behaviour and values. Also identity and expressiveness are present and it is evaluated whether travel services facilitate these constructs. The topic is approached by discovering the key concepts such as self-identity. This was done in order to create survey questions that reflect the underlying theories. The survey was sent to chosen student groups of Turku School of Economics. The data was analyzed using statistical methods, mainly principal component analysis, in order to categorize students��� motives and behaviour into distinct profiles. The findings indicate that students have a high level of awareness in their travel consumption choices. Travel services seem to facilitate identity and lifestyle expressiveness, one central dimension of postmodernity. Psychographics such as motivation seem to work well as a segmentation criteria when it comes to the student traveler market. Travel offers students an opportunity for relaxation, escape, enjoyment and gaining new experiences and social contacts. Furthermore, the enjoyment of the travel experience extends to the pre- and post-trip time.

User Experience Patterns for/of Innovation by Design: A Survey on Design Practices in the Software Development and Innovation Lifecycle

The User Experience (UX) designers are undoubtedly aware of how many UX design methods currently exist and that sometimes it becomes a problem to choose an appropriate one. What are all of methods that designers have in their ���arsenal���? When can they use them? This thesis presents the research on the design methods in the contemporary context of User Experience (UX) and Innovations by using a survey approach. The study is limited to cover the domain of consumer mobile services development and provider companies around the world. The study follows 2 clear objectives: (1) to understand what design methods are currently used in that context and to what extent they are used (2) to identify at what stage according to the UX design thinking process for creating innovations they are placed. The study contributes to the research in the field of UX design and Innovations and extends the knowledge in that field together with communities��� (UXPA, SIGCHI, SIGSOFT) members��� cooperation. The research is vital due to lack of information on design practices and their application in the chosen context.