157 research outputs found

    Koronapandemian vaikutukset henkilöasiakkaiden asuntolainoihin suomessa

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    Tiivistelmä. Tämän kandidaatintutkielman aiheena on luoda katsaus Covid-19-pandemian vaikutuksista suomalaisten henkilöasiakkaiden asuntolainoihin. Tutkielmassa aihetta lähestytään tutkimalla kahtena pääkohteena lainojen hakumäärien- sekä maksukyvyn muutoksia ja syitä. Jotta muutoksia voidaan tarkastella historiallisessa perspektiivissä, verrataan pandemian vaikutuksia muihin taloudellisesti merkittäviin aikaperiodeihin. Tutkielman johdannossa tutustutaan aiheeseen sekä perusteluihin sen valinnalle. Tätä seuraavat tutkimuksen tavoite ja ongelma, tiivistetty metodologia sekä keskeisten käsitteiden määrittely. Luvussa kaksi muodostetaan tutkielman teoreettinen viitekehys, johon empiirisen tutkimuksen tuloksia voidaan verrata. Itse empiirinen tutkimusmenetelmä sekä aineiston data käydään tarkemmin läpi luvussa kolme, jotta analyysi voidaan toteuttaa luvussa neljä. Viimeisessä luvussa käydään läpi johtopäätökset tutkielmast

    Altered Metabolic Profile in Congenital Lung Lesions Revealed by1H Nuclear Magnetic Resonance Spectroscopy

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    Congenital lung lesions are highly complex with respect to pathogenesis and treatment. Large-scale analytical methods, like metabolomics, are now available to identify biomarkers of pathological phenotypes and to facilitate clinical management. Nuclear magnetic resonance (NMR) is a unique tool for translational research, as in vitro results can be potentially translated into in vivo magnetic resonance protocols. Three surgical biopsies, from congenital lung malformations, were analyzed in comparison with one control sample. Extracted hydrophilic metabolites were submitted to high resolution 1H NMR spectroscopy and the relative concentration of 12 metabolites was estimated. In addition, two-dimensional NMR measurements were performed to complement the results obtained from standard monodimensional experiments. This is one of the first reports of in vitro metabolic profiling of congenital lung malformation. Preliminary data on a small set of samples highlights some altered metabolic ratios, dealing with the glucose conversion to lactate, to the relative concentration of phosphatidylcholine precursors, and to the presence of myoinositol. Interestingly some relations between congenital lung lesions and cancer metabolic alterations are found

    Conversion of the Native N-Terminal Domain of TDP-43 into a Monomeric Alternative Fold with Lower Aggregation Propensity

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    TAR DNA-binding protein 43 (TDP-43) forms intraneuronal cytoplasmic inclusions associated with amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. Its N-terminal domain (NTD) can dimerise/oligomerise with the head-to-tail arrangement, which is essential for function but also favours liquid-liquid phase separation and inclusion formation of full-length TDP-43. Using various biophysical approaches, we identified an alternative conforma-tional state of NTD in the presence of Sulfobetaine 3-10 (SB3-10), with higher content of α-helical structure and tryptophan solvent exposure. NMR shows a highly mobile structure, with partially folded regions and β-sheet content decrease, with a concomitant increase of α-helical structure. It is monomeric and reverts to native oligomeric NTD upon SB3-10 dilution. The equilibrium GdnHCl-induced denaturation shows a cooperative folding and a somewhat lower conformational stability. When the aggregation processes were compared with and without pre-incubation with SB3-10, but at the identical final SB3-10 concentration, a slower aggregation was found in the former case, despite the reversible attainment of the native conformation in both cases. This was attributed to protein monomerization and oligomeric seeds disruption by the conditions promoting the alternative con-formation. Overall, the results show a high plasticity of TDP-43 NTD and identify strategies to monomerise TDP-43 NTD for methodological and biomedical applications

    Metabolomic profile of amniotic fluid to evaluate lung maturity: the diaphragmatic hernia lamb model

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    Background: Tracheal occlusion (TO) stimulates lung growth in fetuses affected with congenital diaphragmatic hernia (CDH) although the processes involved in lung maturation still remain unknown. The objective of this study was to evaluate the metabolomic profile of amniotic fluid (AF) following TO in fetal lamb model in order to obtain an indirect view of mechanisms involved in pulmonary reversal hypoplasia and biochemical maturity in response to fetal TO. Methods: Liquid Chromatography Mass Spectrometry was performed on lamb AF samples at: age I (70 days' gestation); age II (102 days' gestation); age III (136 days' gestation). CDH was induced at age I and TO at age II. Results: Betaine, choline, creatinine were found significantly increased during gestation in the control group. The CDH group showed choline (p =0.007) and creatinine (p =0.004) decreases during pregnancy. In the TO group choline and creatinine profiles were restored. Conclusions: Alveolar tissue and fetal global growth ameliorated after TO. Metabolomics provided usefu information on biochemical details during lung maturation. Metabolomic profiling would help to identify the best time to perform TO, in order to increase survival of CDH affected patients

    The regulatory landscape of plastic governance - a Norwegian perspective

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    In this report we co-produced a matrix of governance fragmentation in the Norwegian plastic value chain to assess where there are overlaps, interplay and synergies to be aligned. This also included an assessment of the global level of plastic regulatory fragmentation as it relates to the upcoming negotiations for a global treaty to end plastic pollution.Norges forskningsrådpublishedVersio

    Insights into Thymus Development and Viral Thymic Infections

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    T-cell development in the thymus is a complex and highly regulated process, involving a wide variety of cells and molecules which orchestrate thymocyte maturation into either CD4+ or CD8+ single-positive (SP) T cells. Here, we briefly review the process regulating T-cell differentiation, which includes the latest advances in this field. In particular, we highlight how, starting from a pool of hematopoietic stem cells in the bone marrow, the sequential action of transcriptional factors and cytokines dictates the proliferation, restriction of lineage potential, T-cell antigen receptors (TCR) gene rearrangements, and selection events on the T-cell progenitors, ultimately leading to the generation of mature T cells. Moreover, this review discusses paradigmatic examples of viral infections affecting the thymus that, by inducing functional changes within this lymphoid gland, consequently influence the behavior of peripheral mature T-lymphocytes

    IBtkα Activates the β‐Catenin‐Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3βin Cancerous B Cells

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    The IBTK gene encodes the IBtkα protein that is a substrate receptor of E3 ubiquitin ligase, Cullin 3. We have previously reported the pro‐tumorigenic activity of Ibtk in MYC‐dependent B‐ lymphomagenesis observed in Eμ‐myc transgenic mice. Here, we provide mechanistic evidence of the functional interplay between IBtkα and MYC. We show that IBtkα, albeit indirectly, activates the β‐catenin‐dependent transcription of the MYC gene. Of course, IBtkαassociates with GSK3β and promotes its ubiquitylation, which is associated with proteasomal degradation. This event increases the protein level of β‐catenin, a substrate of GSK3β, and results in the transcriptional activation of the MYC and CCND1 target genes of β‐catenin, which are involved in the control of cell division and apoptosis. In particular, we found that in Burkitt’s lymphoma cells, IBtkα silencing triggered the downregulation of both MYC mRNA and protein expression, as well as a strong decrease of cell survival, mainly through the induction of apoptotic events, as assessed by using flow cytometry‐based cell cycle and apoptosis analysis. Collectively, our results shed further light on the complex puzzle of IBtkα interactome and highlight IBtkα as a potential novel therapeutic target to be employed in the strategy for personalized therapy of B cell lymphoma

    Migrant pathways to community mental health centres in Italy.

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    Background: Many studies indicate that migrants in western countries have limited access to and low utilization of community mental health centres (CMHCs) despite the high prevalence of mental disorders. Aims: We aimed to compare migrant pathways to care across four CMHCs located in different Italian provinces and to identify pathway to care predictors. Methods: Migrants attending the four CMHCs between 1 July 1999 and 31 December 2007 were included in the study. Data were gathered retrospectively from clinical data sets and chart review. Results: Five hundred and eleven (511) migrants attended the four CMHCs, 61% were referred by GPs or other health services and 39% followed non-medical pathways to care (self-referral or through social and voluntary organizations), with important site variations. Younger age and being married were predictors of medical pathways to care; lacking a residence permit and having a diagnosis of substance abuse were related to non-medical pathways. Conclusions: Pathways to CMHCs are complex and influenced by many factors. Non-medical pathways to care seem to be frequent among migrants in Italy. More attention should be paid to developing psychiatric consultation liaison models that also encompass the social services and voluntary organizations

    Migrant pathways to community mental health centres in Italy.

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    Background: Many studies indicate that migrants in western countries have limited access to and low utilization of community mental health centres (CMHCs) despite the high prevalence of mental disorders. Aims: We aimed to compare migrant pathways to care across four CMHCs located in different Italian provinces and to identify pathway to care predictors. Methods: Migrants attending the four CMHCs between 1 July 1999 and 31 December 2007 were included in the study. Data were gathered retrospectively from clinical data sets and chart review. Results: Five hundred and eleven (511) migrants attended the four CMHCs, 61% were referred by GPs or other health services and 39% followed non-medical pathways to care (self-referral or through social and voluntary organizations), with important site variations. Younger age and being married were predictors of medical pathways to care; lacking a residence permit and having a diagnosis of substance abuse were related to non-medical pathways. Conclusions: Pathways to CMHCs are complex and influenced by many factors. Non-medical pathways to care seem to be frequent among migrants in Italy. More attention should be paid to developing psychiatric consultation liaison models that also encompass the social services and voluntary organizations

    Human wild-type and D76N β_{2}-microglobulin variants are significant proteotoxic and metabolic stressors for transgenic C. elegans

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    β2-microglobulin (β2-m) is a plasma protein derived from physiological shedding of the class I major histocompatibility complex (MHCI), causing human systemic amyloidosis either due to persistently high concentrations of the wild-type (WT) protein in hemodialyzed patients, or in presence of mutations, such as D76N β2-m, which favor protein deposition in the adulthood, despite normal plasma levels. Here we describe a new transgenic Caenorhabditis elegans (C. elegans) strain expressing human WT β2-m at high concentrations, mimicking the condition that underlies dialysis-related amyloidosis (DRA) and we compare it to a previously established strain expressing the highly amyloidogenic D76N β2-m at lower concentrations. Both strains exhibit behavioral defects, the severity of which correlates with β2-m levels rather than with the presence of mutations, being more pronounced in WT β2-m worms. β2-m expression also has a deep impact on the nematodes' proteomic and metabolic profiles. Most significantly affected processes include protein degradation and stress response, amino acids metabolism, and bioenergetics. Molecular alterations are more pronounced in worms expressing WT β2-m at high concentration compared to D76N β2-m worms. Altogether, these data show that β2-m is a proteotoxic protein in vivo also in its wild-type form, and that concentration plays a key role in modulating pathogenicity. Our transgenic nematodes recapitulate the distinctive features subtending DRA compared to hereditary β2-m amyloidosis (high levels of non-mutated β2-m vs. normal levels of variant β2-m) and provide important clues on the molecular bases of these human diseases
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