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Search Results: 1 - 10 of 400816 matches for " Heini M. Miettinen "
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Regulation of Human Formyl Peptide Receptor 1 Synthesis: Role of Single Nucleotide Polymorphisms, Transcription Factors, and Inflammatory Mediators
Heini M. Miettinen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0028712
Abstract: The gene encoding the human formyl peptide receptor 1 (FPR1) is heterogeneous, containing numerous single nucleotide polymorphisms (SNPs). Here, we examine the effect of these SNPs on gene transcription and protein translation. We also identify gene promoter sequences and putative FPR1 transcription factors. To test the effect of codon bias and codon pair bias on FPR1 expression, four FPR1 genetic variants were expressed in human myeloid U937 cells fused to a reporter gene encoding firefly luciferase. No significant differences in luciferase activity were detected, suggesting that the translational regulation and protein stability of FPR1 are modulated by factors other than the SNP codon bias and the variant amino acid properties. Deletion and mutagenesis analysis of the FPR1 promoter showed that a CCAAT box is not required for gene transcription. A ?88/41 promoter construct resulted in the strongest transcriptional activity, whereas a ?72/41 construct showed large reduction in activity. The region between ?88 and ?72 contains a consensus binding site for the transcription factor PU.1. Mutagenesis of this site caused significant reduction in reporter gene expression. The PU.1 binding was confirmed in vivo by chromatin immunoprecipitation, and the binding to nucleotides ?84 to ?76 (TTCCTATTT) was confirmed in vitro by an electrophoretic mobility shift assay. Thus, similar to many other myeloid genes, FPR1 promoter activity requires PU.1. Two single nucleotide polymorphisms at ?56 and ?54 did not significantly affect FPR1 gene expression, despite differences in binding of transcription factor IRF1 in vitro. Inflammatory mediators such as interferon-γ, tumor necrosis factor-α, and lipopolysaccharide did not increase FPR1 promoter activity in myeloid cells, whereas differentiation induced by DMSO and retinoic acid enhanced the activity. This implies that the expression of FPR1 in myeloid cells is developmentally regulated, and that the differentiated cells are equipped for immediate response to microbial infections.
In Vivo and In Vitro Study of a Polylactide-Fiber-Reinforced β-Tricalcium Phosphate Composite Cage in an Ovine Anterior Cervical Intercorporal Fusion Model
Janek Frantzén,Aliisa P lli,Esa Kotilainen,Harri Heino,Bettina Mannerstr m,Heini Huhtala,Hannu Kuokkanen,George K. Sándor,Kari Leino,Matias R ytt ,Riitta Parkkola,Riitta Suuronen,Susanna Miettinen,Hannu T. Aro,Suvi Haimi
International Journal of Biomaterials , 2011, DOI: 10.1155/2011/109638
Abstract: A poly-70L/30DL-lactide (PLA70)–β-tricalcium phosphate (β-TCP) composite implant reinforced by continuous PLA-96L/4D-lactide (PLA96) fibers was designed for in vivo spinal fusion. The pilot study was performed with four sheep, using titanium cage implants as controls. The composite implants failed to direct bone growth as desired, whereas the bone contact and the proper integration were evident with controls 6 months after implantation. Therefore, the PLA70/β-TCP composite matrix material was further analyzed in the in vitro experiment by human and ovine adipose stem cells (hASCs and oASCs). The composites proved to be biocompatible as confirmed by live/dead assay. The proliferation rate of oASCs was higher than that of hASCs at all times during the 28 d culture period. Furthermore, the composites had only a minor osteogenic effect on oASCs, whereas the hASC osteogenesis on PLA70/β-TCP composites was evident. In conclusion, the composite implant material can be applied with hASCs for tissue engineering but not be evaluated in vivo with sheep.
Culture Conditions Affect Cardiac Differentiation Potential of Human Pluripotent Stem Cells
Marisa Ojala, Kristiina Rajala, Mari Pekkanen-Mattila, Marinka Miettinen, Heini Huhtala, Katriina Aalto-Set?l?
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048659
Abstract: Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), are capable of differentiating into any cell type in the human body and thus can be used in studies of early human development, as cell models for different diseases and eventually also in regenerative medicine applications. Since the first derivation of hESCs in 1998, a variety of culture conditions have been described for the undifferentiated growth of hPSCs. In this study, we cultured both hESCs and hiPSCs in three different culture conditions: on mouse embryonic fibroblast (MEF) and SNL feeder cell layers together with conventional stem cell culture medium containing knockout serum replacement and basic fibroblast growth factor (bFGF), as well as on a Matrigel matrix in mTeSR1 medium. hPSC lines were subjected to cardiac differentiation in mouse visceral endodermal-like (END-2) co-cultures and the cardiac differentiation efficiency was determined by counting both the beating areas and Troponin T positive cells, as well as studying the expression of OCT-3/4, mesodermal Brachyury T and NKX2.5 and endodermal SOX-17 at various time points during END-2 differentiation by q-RT-PCR analysis. The most efficient cardiac differentiation was observed with hPSCs cultured on MEF or SNL feeder cell layers in stem cell culture medium and the least efficient cardiac differentiation was observed on a Matrigel matrix in mTeSR1 medium. Further, hPSCs cultured on a Matrigel matrix in mTeSR1 medium were found to be more committed to neural lineage than hPSCs cultured on MEF or SNL feeder cell layers. In conclusion, culture conditions have a major impact on the propensity of the hPSCs to differentiate into a cardiac lineage.
Er fru Ruben j disk eller ikke? En dr fting av hennes karakter i Hamsuns Siste Kapitel
Heini M?h?nen,Anna Klara M?seide
Nordlit : Tidsskrift i litteratur og kultur , 2005,
Abstract: I denne artikkelen vil vi diskutere karakteren fru Ruben fra Hamsuns roman Siste Kapitel, som utkom i 1923. I sammenheng med denne karakteren nsker vi se henne i lys av Allen Simpsons artikkel "Knut Hamsun's Anti-Semitism" der han kaller henne for "Hamsun`s most offensive anti-Semitic fictional creation." Simpson argumenterer her for at Hamsun ved flere anledninger bekjentgj r sine politiske standpunkt og tydeliggj r dem gjennom diktningen sin. Dette kommer allerede frem ved en av artikkelens mellomtitler, "Anti-Semitism in Hamsun's Authorship", som peker mot en lesning av Hamsun og hans forfatterskap som vanskelig kan misforst s. Simpsons argumentasjonsmetode later ikke til ta hensyn til n dvendigheten av en narratologisk analyse; istedenfor virker det som om argumentasjonen baseres p Hamsuns liv, hans kulturelle og politiske sympatier og antipatier. En slik bruk av historisk-biografisk opplysninger kan v re problematisk, fordi teksten selv risikerer bli tilsidesatt. Simpson hevder at Hamsun i Siste Kapitel klart knytter an til anti-semittiske referanser, slik som navn, bruk av terminologi, utseende og andre klisjeer om j der og han knytter disse opp til karakteren fru Ruben. Han konkluder med at hun m v re j disk, til tross for en sl ende mangel p konkret tekstlig belegg omkring karakterens religi se og kulturelle tilknytning. P bakgrunn av Simpsons sterke p stand kombinert med mangelfull tekstlig illustrasjon, nsker vi dr fte fru Rubens j diske opphav.
Er fru Ruben j disk eller ikke? En dr fting av hennes karakter i Hamsuns Siste Kapitel
Heini M?h?nen,Anna Klara M?seide
Nordlit : Tidsskrift i litteratur og kultur , 2005,
Abstract: I denne artikkelen vil vi diskutere karakteren fru Ruben fra Hamsuns roman Siste Kapitel, som utkom i 1923. I sammenheng med denne karakteren nsker vi se henne i lys av Allen Simpsons artikkel "Knut Hamsun's Anti-Semitism" der han kaller henne for "Hamsun`s most offensive anti-Semitic fictional creation." Simpson argumenterer her for at Hamsun ved flere anledninger bekjentgj r sine politiske standpunkt og tydeliggj r dem gjennom diktningen sin. Dette kommer allerede frem ved en av artikkelens mellomtitler, "Anti-Semitism in Hamsun's Authorship", som peker mot en lesning av Hamsun og hans forfatterskap som vanskelig kan misforst s. Simpsons argumentasjonsmetode later ikke til ta hensyn til n dvendigheten av en narratologisk analyse; istedenfor virker det som om argumentasjonen baseres p Hamsuns liv, hans kulturelle og politiske sympatier og antipatier. En slik bruk av historisk-biografisk opplysninger kan v re problematisk, fordi teksten selv risikerer bli tilsidesatt. Simpson hevder at Hamsun i Siste Kapitel klart knytter an til anti-semittiske referanser, slik som navn, bruk av terminologi, utseende og andre klisjeer om j der og han knytter disse opp til karakteren fru Ruben. Han konkluder med at hun m v re j disk, til tross for en sl ende mangel p konkret tekstlig belegg omkring karakterens religi se og kulturelle tilknytning. P bakgrunn av Simpsons sterke p stand kombinert med mangelfull tekstlig illustrasjon, nsker vi dr fte fru Rubens j diske opphav.
High degree of sex chromosome differentiation in stickleback fishes
Takahito Shikano, Heini M Natri, Yukinori Shimada, Juha Meril?
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-474
Abstract: A set of novel microsatellite markers spanning the entire length of the sex chromosomes were developed for nine-spined sticklebacks using the sequenced genomes of other fish species. Sex-specific patterns of genetic variability and male-specific alleles were identified at most of these loci, indicating a high degree of differentiation between the X and Y chromosomes in nine-spined sticklebacks. In three-spined sticklebacks, male-specific alleles were detected at some loci confined to two chromosomal regions. In addition, male-specific null alleles were identified at several other loci, implying the absence of Y chromosomal alleles at these loci. Overall, male-specific alleles and null alleles were found over a region spanning 81% of the sex chromosomes in three-spined sticklebacks.High levels but distinct patterns of sex chromosome differentiation were uncovered in the stickleback species that diverged 13 million years ago. Our results suggest that the Y chromosome is highly degenerate in three-spined sticklebacks, but not in nine-spined sticklebacks. In general, the results demonstrate that microsatellites can be useful in identifying the degree and patterns of sex chromosome differentiation in species at initial stages of sex chromosome evolution.Recent advances in comparative genomic and molecular cytogenetic studies have greatly increased our understanding about the extent and pace of sex chromosome evolution [1,2]. For instance, therian and avian sex chromosomes are known to have originated independently from two different autosomal regions in a common ancestor [1,3]. In contrast, lower vertebrates exhibit a wide variety of sex chromosome and sex determination systems, implying multiple and independent origins of sex chromosomes [4-6]. Recent studies have shown that sex chromosomes of Oryzias fishes and sticklebacks (Gasterosteidae) have emerged 10 million years ago or even later [7-10]. Likewise, different heterogametic sex determination systems have been foun
Long-Term Consumption of Oats in Adult Celiac Disease Patients
Katri Kaukinen,Pekka Collin,Heini Huhtala,Markku M?ki
Nutrients , 2013, DOI: 10.3390/nu5114380
Abstract: Many celiac disease patients tolerate oats, but limited data are available on its long-term consumption. This was evaluated in the present study, focusing on small-bowel mucosal histology and gastrointestinal symptoms in celiac adults maintaining a strict gluten-free diet with or without oats. Altogether 106 long-term treated celiac adults were enrolled for this cross-sectional follow-up study. Daily consumption of oats and fiber was assessed, and small-bowel mucosal morphology and densities of CD3+, αβ+ and γσ+ intraepithelial lymphocytes determined. Gastrointestinal symptoms were assessed by a validated Gastrointestinal Symptom Rating Scale questionnaire. Seventy (66%) out of the 106 treated celiac disease patients had consumed a median of 20 g of oats (range 1–100 g) per day for up to eight years; all consumed oat products bought from general stores. Daily intake and long-term consumption of oats did not result in small-bowel mucosal villous damage, inflammation, or gastrointestinal symptoms. Oat-consumers had a significantly higher daily intake of fiber than those who did not use oats. Two thirds of celiac disease patients preferred to use oats in their daily diet. Even long-term ingestion of oats had no harmful effects.
AIDS-Related EBV-Associated Smooth Muscle Tumors: A Review of 64 Published Cases
Bibianna Purgina,Uma N. M. Rao,Markku Miettinen,Liron Pantanowitz
Pathology Research International , 2011, DOI: 10.4061/2011/561548
Abstract: The number of reported cases of smooth muscle tumor (SMT) arising in patients with AIDS has been increasing since the mid-1990s. The aim of this study is to characterize the epidemiology, clinical manifestations, pathologic features, prognosis and, management of Epstein-Barr virus-related SMT (EBV-SMT) in patients with AIDS. An English language literature search identified 53 articles including 64 reported cases of EBV-SMT. The majority of these reports involved patients who were young, severely immunosuppressed, and had multifocal tumors. The central nervous system was the most common site to be involved. Histologically, tumors had smooth muscle features and were immunoreactive for muscle markers and all but two tumors demonstrated the presence of EBV by either immunohistochemistry, in situ hybridization, and/or PCR. While mitoses and/or necrosis were used to separate leiomyoma from leiomyosarcoma, these features did not correlate with clinical outcome. Treatment included primarily resection, and less often radiotherapy, chemotherapy and highly active antiretroviral therapy (HAART). Overall, EBV-SMTs appear to have variable aggressiveness and clinical outcome and may exhibit a more favorable prognosis compared to conventional leiomyosarcoma. Tumor-related death from EBV-SMT occurred in only 4 of 51 patients. 1. Introduction An increased rate of both acquired immune deficiency syndrome (AIDS) defining cancers (e.g., Kaposi sarcoma, B-cell non-Hodgkin lymphoma, uterine cervical neoplasia) and non-AIDS defining cancers (NADC) like Hodgkin lymphoma, anal cancer, and lung cancer is a well established phenomenon in patients with AIDS. As the human immunodeficiency virus (HIV) pandemic persists and more people are living with chronic HIV infection, the rate and spectrum of NADC continue to grow. There are increasing numbers of case reports and small case series in the literature documenting the occurrence of smooth muscle tumors (SMT) in the adult and pediatric population suffering from AIDS. In fact, SMTs including malignant leiomyosarcoma, prior to the AIDS epidemic, were exceedingly rare in the pediatric population. Now, SMTs appear to be the second most common type of neoplasm arising in children with AIDS [1–3]. EBV-SMT also occurs in posttransplant immunosuppressed patients and individuals with other causes of immunosuppression such as autoimmune disease and common variable immunodeficiency syndrome [4, 5]. Coinfection with Epstein-Barr Virus (EBV) appears to be a necessary cofactor for the development of these tumors. Hence, these tumors have aptly
Nanoparticle formation by ozonolysis of inducible plant volatiles
J. Joutsensaari,M. Loivam?ki,T. Vuorinen,P. Miettinen
Atmospheric Chemistry and Physics Discussions , 2005,
Abstract: We present the first laboratory experiments of aerosol formation from oxidation of volatile organic species emitted by living plants, a process which for half a century has been known to take place in the atmosphere. We have treated white cabbage crops with methyl jasmonate in order to induce the production of monoterpenes and certain less-volatile sesqui- and homoterpenes. Ozone was introduced into the growth chamber in which the crops were placed, and the subsequent aerosol formation and growth of aerosols were monitored by measuring the particle size distributions continuously during the experiments. Our observations show similar particle formation rates as in the atmosphere but much higher growth rates. The results indicate that the concentrations of nonvolatile oxidation products of plant released precursors needed to induce the nucleation are roughly an order-of-magnitude higher than their concentrations during atmospheric nucleation events. Our results therefore suggest that atmospheric nucleation events proceed via condensation of oxidized organics on pre-existing molecular clusters rather than via their homogeneous or ion-induced nucleation.
Digital Health Platform Complementor Strategies and Effectual Reasoning  [PDF]
Anssi Smedlund, Petra Turkama, Heini Ik?valko
Journal of Service Science and Management (JSSM) , 2018, DOI: 10.4236/jssm.2018.114025
Abstract: Digital platform based markets are starting to dominate many sectors of the economy and society. Apple Healthkit and Google Fit are examples of fitness data platforms and focal points of connected preventive healthcare markets. Application developers are increasingly complementing platforms instead of bringing stand-alone services to the market. However, studies on these complementors’ strategies are still rare. This paper examines complementors’ strategies in joining digital platforms in preventive healthcare sector through an exploratory case study. The strategies are created by identifying themes and subthemes from interviews with complementors, and evaluating them through effectual reasoning lens. Effectual reasoning is selected as the assessment approach due to increased ecosystem complexity and strategic choices caused by accumulating end-user data, processes, user experience and emerging communities. This paper states that complementors can attach their application not only to the stable technological core maintained by the platform owner, but also dynamic elements being co-created among other platform participants. The paper contributes to the ongoing discussion and platform literature on complementor strategies.
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