Online measurements of real-time cytotoxic responses induced by multi-component matrices, such as natural products, through electric-cell substrate impedance sensing (ECIS).

Natural products are complex matrices of compounds that are prone to interfere with the label-dependent methods that are typically used for cytotoxicity screenings. Here, we developed a label-free Electric Cell-substrate Impedance Sensing (ECIS)-based cytotoxicity assay that can be applied in the assessment of the cytotoxicity of natural extracts. The conditions to measure the impedance using ECIS were first optimized in mice immortalized hypothalamic neurons GT1-7 cells. The performance of four natural extracts when tested using three conventional cytotoxicity assays in GT1-7 cells, was studied. Betula pendula (silver birch tree) was found to interfere with all of the cytotoxicity assays in which labels were applied. The silver birch extract was also proven to be cytotoxic and, thus, served as a proof-of-concept for the use of ECIS. The extract was fractionated and the ECIS method permitted the distinction of specific kinetic patterns of cytotoxicity on the fractions as well as the extract's pure constituents. This study offers evidence that ECIS is an excellent tool for real-time monitoring of the cytotoxicity of complex extracts that are difficult to work with using conventional (label-based) assays. Altogether, it offers a very suitable cytotoxicity-screening assay making the work with natural products less challenging within the drug discovery workflow.Peer reviewe

Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism

Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37(-/-)) model for MUL. Trim37(-/-) mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37(-/-) mice as compared with wildtype. Both male and female Trim37(-/-) mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37(-/-) mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37(-/-) mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37(-/-) mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37(-/-) mice. The most consistently seen phenotypes in Trim37(-/-) mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37(-/-) mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis.Peer reviewe

Yksilölliset toiveet asuntotuotannossa

Abstract This publication is the final report of the research project, funded by the Academy of Finland in 2004 and 2005, entitled Individual wishes in the mass production of housing architecture. The research locations were Arabianranta in Helsinki, and Toppilansaari housing fair area of 2005 in Oulu. This multidisciplinary research has been done to serve the practical fields of construction and architecture. The writers focused on different aspects in the study: Noora Ervasti and Elina Pietikäinen, both M.Sc. in Economics, studied the individual wishes in apartment house production, CASE Toppilansaari in Oulu; Landscape Architect Eva Wiklund looked at Arabianranta as a housing environment; Interior Architect Maarit Hiltunen studied Open construction as a way to fulfil individual wishes; and Interior Architect Esa Vesmanen concentrated on the Customer's possibilities in influencing the outcome of the kitchen in Arabianranta. It can be concluded that the customers looking for an apartment are more demanding and know what they want. This presupposes new means from the housing industry and a more modular production process in which the result is an apartment that best fulfils the individual wishes. This new way to produce requires configuring and developing in the whole process chain of housing production.Tiivistelmä Tämä julkaisu on loppuraportti Suomen Akatemian vuosina 2004–2005 rahoittamaan projektiin Yksilöllisten toiveiden toteutuminen asuntoarkkitehtuurin massatuotannossa. Tutkimuksen kohdealueita olivat Helsingin Arabianranta ja Oulun Toppilansaaren vuoden 2005 asuntomessualue. Tämä monitieteinen tutkimus on tehty palvelemaan rakentamisen ja arkkitehtuurin käytännön kenttää. Loppuraportin artikkelien kirjoittajista kauppatiet.maistereiden Noora Ervastin ja Elina Pietikäisen aiheena oli Yksilöllisten asumistoiveiden toteutuminen kerrostalotuotannossa, CASE: Oulun Toppilansaari. Maisema-arkkitehti Eva Wiklund tarkasteli Arabianrantaa asuin-ympäristönä asukkaiden näkökulmasta ja sisustusarkkitehti Maarit Hiltusen aiheena oli Joustavan rakentamisen keinot yksilöllisyyden toteutumisessa. Sisustusarkkitehti Esa Vesmanen keskittyi tutkimaan asukkaan vaikutusmahdollisuuksia asunnon keittiöön Arabianrannassa. Asuntoa etsivät asiakkaat ovat entistä vaativampia ja tietävät mitä haluavat. Tämä edellyttää rakennusteollisuudelta uudenlaisia keinoja ja entistä modulaarisempaa tuotantoprosessia, jossa lopputuloksena on yksilölliset toiveet parhaiten täyttävä asunto

Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata

Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.Peer reviewe