Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model

BACKGROUND: The TGFβ1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFβ1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new players in epithelial cell differentiation. RESULTS: The expression of 372 genes out of 5188 arrayed sequences was significantly altered, and 47 of them were altered by both mediators. The data were validated and the altered genes are presented in ontology classes. For the genes tested the expressions in protein level were in accordance with the mRNA results. We also found 194 genes with no known function to be potentially important in epithelial cell differentiation. The mRNA expression changes induced by TGFβ1 were bigger than changes induced by soluble factors secreted by IMR-90 mesenchymal cells. The gene expression data was depicted in already known signaling pathway routes. CONCLUSION: Our results reveal potential new signaling pathways and several new genes affected by TGFβ in epithelial cell differentiation. The differentiation induced by TGFβ1 appears to be more potent than the differentiation induced by mesenchymal cells. This study indicates that our cell culture model is a suitable tool in studying regulatory mechanisms during epithelial cell differentiation in intestine. Furthermore the present results indicate that our model is a good tool for finding new players acting in the differentiation of epithelial cells

Influence of Hsp90 and HDAC Inhibition and Tubulin Acetylation on Perinuclear Protein Aggregation in Human Retinal Pigment Epithelial Cells

Retinal pigment epithelial (RPE) cells are continually exposed to oxidative stress that contributes to protein misfolding, aggregation and functional abnormalities during aging. The protein aggregates formed at the cell periphery are delivered along the microtubulus network by dynein-dependent retrograde trafficking to a juxtanuclear location. We demonstrate that Hsp90 inhibition by geldanamycin can effectively suppress proteasome inhibitor, MG-132-induced protein aggregation in a way that is independent of HDAC inhibition or the tubulin acetylation levels in ARPE-19 cells. However, the tubulin acetylation and polymerization state affects the localization of the proteasome-inhibitor-induced aggregation. These findings open new perspectives for understanding the pathogenesis of protein aggregation in retinal cells and can be useful for the development of therapeutic treatments to prevent retinal cell deterioration

Food insecurity among Finnish private service sector workers : validity, prevalence and determinants

Objective: To examine the prevalence and determinants of food insecurity among private sector service workers in Finland and assess validity of the Household Food Insecurity Access Scale (HFIAS) tool. Design: In this cross-sectional study, food insecurity and background characteristics were collected from Finnish private service workers via electronic questionnaires (2019) and national register data (2018-2019). We conducted univariate and multivariate logistic regression analyses to determine the variables explaining food insecurity. Validity of HFIAS was assessed with rotated principal component analysis and Cronbach's alpha. Setting: Members of the trade union for private sector service workers, Service Union United (PAM), from all municipalities in Finland participated in the study in 2019. Participants: The subjects were 6435 private sector workers that were members of the Service Union United (PAM) in Finland. Mean age of participants was 44 years (sd 12 center dot 7 years). Results: Two-thirds of the participants (65 %) were food insecure with over a third (36 %) reporting severe food insecurity. Reporting great difficulties in covering household expenses and young age markedly increased the risk of severe food insecurity (OR 15 center dot 05; 95 % CI 10 center dot 60, 21 center dot 38 and OR 5 center dot 07; 95 % CI 3 center dot 94, 6 center dot 52, respectively). Not being married, low education, working in the hospitality industry, being male and living in rented housing also increased the probability of severe food insecurity. The HFIAS tool demonstrated acceptable construct and criterion validity. Conclusions: Severe food insecurity was widespread and associated with low socio-economic status, young age and being male among Finnish private sector service workers, emphasising the need for regular monitoring of food insecurity in Finland.Peer reviewe

Performance and flow dynamics studies of polymeric optofluidic sers sensors

We present a polymer-based optofluidic surface enhanced Raman scattering chip for biomolecule detection, serving as a disposable sensorchoice with cost-effective production. The SERS substrate is fabricated by using industrial roll-to-roll UV-nanoimprinting equipment andintegrated with adhesive-based polymeric microfluidics. The functioning of the SERS detection on-chip is confirmed and the effect of thepolymer lid on the obtainable Raman spectra is analysed. Rhodamine 6G is used as a model analyte to demonstrate continuous flowmeasurements on a planar SERS substrate in a microchannel. The relation between the temporal response of the sensors and sample flowdynamics is studied with varied flow velocities, using SERS and fluorescence detection. The response time of the surface-dependent SERSsignal is longer than the response time of the fluorescence signal of the bulk flow. This observation revealed the effect of convection on thetemporal SERS responses at 25 μl/min to 1000 μl/min flow velocities. The diffusion of analyte molecules from the bulk concentration intothe sensing surface induces about a 40-second lag time in the SERS detection. This lag time, and its rising trend with slower flow velocities, has to be taken into account in future trials of the optofluidic SERS sensor, with active analyte binding on the sensing surface

Pediatric malignancies in neurofibromatosis type 1 : A population-based cohort study

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of 1:2,000. Patients with NF1 have an increased cancer risk and mortality, but there are no population-based cohort studies specifically investigating the risk of childhood malignancies. We used the Finnish NF1 cohort to analyze the incidence, risk and prognosis of malignancies in NF1 patientsPeer reviewe

Sindbis Virus Strains of Divergent Origin Isolated from Humans and Mosquitoes During a Recent Outbreak in Finland

Sindbis virus (SINV) is a mosquito-borne avian hosted virus that is widely distributed in Europe, Africa, Asia, and Oceania. Disease in humans is documented mainly from Northern Europe and South Africa and associated with genotype I. In 2018 under extremely warm climatic conditions, a small outbreak of 71 diagnosed SINV infections was recorded in Finland. We screened 52 mosquito pools (570 mosquitoes) and 223 human sera for SINV with real-time RT-PCR and the positive samples with virus isolation. One SINV strain was isolated from a pool (n = 13) of genusOchlerotatusmosquitoes and three strains from patient serum samples. Complete genome analysis suggested all the isolates to be divergent from one another and related to previous Finnish, Swedish, and German strains. The study provides evidence of SINV strain transfer within Europe across regions with different epidemiological characteristics. Whether these are influenced by different mosquito genera involved in the transmission remains to be studied.Peer reviewe

Shape coexistence at the proton drip-line: First identification of excited states in 180Pb

Excited states in the extremely neutron-deficient nucleus, 180Pb, have been identified for the first time using the JUROGAM II array in conjunction with the RITU recoil separator at the Accelerator Laboratory of the University of Jyvaskyla. This study lies at the limit of what is presently achievable with in-beam spectroscopy, with an estimated cross-section of only 10 nb for the 92Mo(90Zr,2n)180Pb reaction. A continuation of the trend observed in 182Pb and 184Pb is seen, where the prolate minimum continues to rise beyond the N=104 mid-shell with respect to the spherical ground state. Beyond mean-field calculations are in reasonable correspondence with the trends deduced from experiment.Comment: 5 pages, 4 figures, submitted to Phys.Rev.

A novel negevirus isolated from Aedes vexans mosquitoes in Finland

Negeviruses are insect-specific enveloped RNA viruses that have been detected in mosquitoes and sandflies from various geographical locations. Here, we describe a new negevirus from Northern Europe, isolated from pool ofAedes vexansmosquitoes collected in Finland, designated as Mekrijarvi negevirus (MEJNV). MEJNV had a typical negevirus genome organization, is 9,740 nucleotides in length, and has a GC content of 47.53%. The MEJNV genome contains three ORFs, each containing the following identified conserved domains: ORF1 (7,068 nt) encodes a viral methyltransferase, an FtsJ-like methyltransferase, a viral RNA helicase, and an RNA-dependent RNA polymerase, ORF2 (1,242 nt) encodes a putative virion glycoprotein, and ORF3 (660 nt) encodes a putative virion membrane protein. A distinctive feature relative to other currently known negeviruses is a 7-nucleotide-long overlap between ORF1 and ORF2. MEJNV shares the highest sequence identity with Ying Kou virus from China, with 67.71% nucleotide and 75.19% and 59.00% amino acid sequence identity in ORF 1 and ORF 2, respectively. ORF3 had the highest amino acid sequence similarity to Daeseongdong virus 1 and negevirus Nona 1, both with 77.61% identity, and to Ying Kou virus, with 71.22% identity. MEJNV is currently the northernmost negevirus described. Our report supports the view that negeviruses are a globally distributed, diverse group of viruses that can be found from mosquitoes in a wide range of terrestrial biomes from tropical to boreal forests.Peer reviewe