198 research outputs found
De week van... Lisanne Doedens
No full textZoals in elke editie van Bestuurskundige Berichten nemen we ook dit keer een kijkje in het leven van een student. Dit keer is het de beurt aan derdejaarsstudent en tevens dit jaar B.I.L.-bestuurslid Lisanne Doedens. Lisanne bekleedt in het bestuur de functie Commissaris Acquisitie & Alumni
Genetic factors in sudden cardiac death victims with myocardial fibrosis
No full textAbstract
Sudden cardiac death (SCD) is a common mode of death leading to 15 to 20 percent of all mortalities. Up to one fifth of all SCDs are caused by nonischaemic myocardial diseases, and in many of these victims previously diagnosed cardiac conditions are absent. One major shared feature among these individuals is myocardial fibrosis, i.e., fibrotic tissue build-up in the myocardium. This pathological condition can cause arrhythmias and cardiac failure. The aim of this doctoral project was to identify genetic variants predisposing to myocardial fibrosis and SCD and to investigate the function of the identified candidate genes in vitro.
We analysed the genetic background of SCD victims who had either primary myocardial fibrosis (PMF, N = 127) or hypertension-related cardiac hypertrophy (N = 96). All victims were part of the Finnish Genetic Study for Arrhythmic events (FinGesture) which has collected tissue samples and clinical information of approximately 6,000 SCD victims since 1998. Associations of the identified variants with cardiac diseases in Finnish population were investigated in the FinnGen dataset.
Fifty-seven candidate genes were identified, many belonging to pathways contributing to cardiomyocyte survival and extracellular matrix organization. These included Unc-45 myosin chaperone (UNC45A) and OMA1 zinc metallopeptidase (OMA1). Transcriptional changes associated with PMF were identified using 3’mRNA sequencing of heart samples. mRNA sequencing revealed that transcriptomic changes in PMF occur, among others, in genes participating in actin cytoskeleton organization and muscle structure development. UNC45A was upregulated in PMF compared to controls. Knockdown of OMA1 in fibroblasts resulted in increased cell proliferation and collagen production. Knockdown of UNC45A in fibroblasts decreased cell proliferation and collagen production.
In conclusion, the possible role of the identified genes in myocardial fibrosis may facilitate the diagnosis and prevention of myocardial fibrosis and decrease the risk of SCD in persons showing symptoms and their family members. Original papers Skarp, S., Doedens, A., Holmström, L., Izzi, V., Saarimäki, S., Sliz, E., Kettunen, J., Pakanen, L., Kerkelä, R., Pylkäs, K., Huikuri, H. V., Myerburg, R. J., & Junttila, J. (2024). Novel genetic variants associated with primary myocardial fibrosis in sudden cardiac death victims. Journal of Cardiovascular Translational Research, 17(6), 1229–1239. https://doi.org/10.1007/s12265-024-10527-5 https://doi.org/10.1007/s12265-024-10527-5 Self-archived version Doedens, A., Skarp, S., Mattila, O., Laasonen, S., Huikuri, H. V., Junttila, J., & Kerkelä, R. (2026). The role of OMA1 and UNC45A in primary myocardial fibrosis. Manuscript in preparation. Doedens, A., Skarp, S., Holmström, L., Pakanen, L., Saarimäki, S., Kerkelä, R., Pylkäs, K., Huikuri, H. V., & Junttila, J. (2025). Genetic variants associated with cardiac hypertrophy-related sudden cardiac death and cardiovascular outcomes in a Finnish population. Heart, 111(2), 55–61. https://doi.org/10.1136/heartjnl-2024-324623 https://doi.org/10.1136/heartjnl-2024-324623 Tiivistelmä
Sydänperäinen äkkikuolema on yleinen kuolinsyy, joka aiheuttaa 15–20 % kaikista kuolemista. Noin viidesosa kaikista tapauksista johtuu muista kuin iskeemisistä sydänsairauksista, ja monilla ei ole aiemmin diagnosoituja sydänsairauksia. Yksi merkittävä yhteinen piirre sydänperäisillä äkkikuolematapauksilla on sydänlihaksen fibroosi eli sidekudoksen kertyminen sydänlihakseen, mikä voi aiheuttaa rytmihäiriöitä ja sydämen vajaatoimintaa. Tämän väitöskirjatyön tavoitteena oli tunnistaa geneettisiä variantteja, jotka altistavat sydänlihaksen fibroosille, sekä tutkia tunnistettujen kandidaattigeenien toimintaa solumalleissa.
Tutkimusaineisto koostuu äkkikuolematapauksista, joilla ruumiinavauksessa todettiin joko primaari sydänlihasfibroosi (N = 127) tai sydänlihasfibroosi sekä sydämen hypertrofia (N = 96). Kaikki tapaukset olivat osa FinGesture-tutkimusta, jossa on kerätty kudosnäytteitä ja kliinistä tietoa äkkikuolematapauksista vuodesta 1998 lähtien. Tunnistettujen varianttien assosiaatiota sydänsairauksiin suomalaisessa väestössä tutkittiin FinnGen-aineistossa. Tunnistimme yhteensä 57 kandidaattigeeniä, joista monet osallistuvat kardiomyosyyttien selviytymiseen ja soluväliaineen järjestäytymiseen vaikuttaviin signalointireitteihin. Tunnistetuista kandidaattigeeneistä tarkastelimme solukokeissa Unc-45 myosiinichaperonis (UNC45A) ja OMA1 sinkkimetallopeptidaasis (OMA1) toimintaa.
Sydänlihasfibroosiin liittyviä transkriptionaalisia muutoksia tunnistettiin sydännäytteiden 3’mRNA-sekvensoinnin avulla. Transkriptionaalisia muutoksia havaittiin muun muassa aktiinisytoskeletonin järjestäytymiseen ja lihasrakenteen kehitykseen osallistuvissa signalointireiteissä. UNC45A-geenin ekspressiotaso oli korkeampi fibroottisissa sydämissä verrattuna kontrolleihin. OMA1-geenin hiljentäminen lisäsi fibroblastien jakautumista ja kollageenin tuotantoa. UNC45A:n hiljentäminen fibroblasteissa puolestaan vähensi solujen jakaantumista ja kollageenin tuotantoa.
Yhteenvetona voidaan todeta, että tunnistettujen geenien mahdollinen rooli sydänlihaksen fibroosissa voi helpottaa sen diagnosointia ja ennaltaehkäisyä sekä vähentää äkkikuoleman riskiä oireita osoittavilla henkilöillä ja heidän perheenjäsenillään. Osajulkaisut Skarp, S., Doedens, A., Holmström, L., Izzi, V., Saarimäki, S., Sliz, E., Kettunen, J., Pakanen, L., Kerkelä, R., Pylkäs, K., Huikuri, H. V., Myerburg, R. J., & Junttila, J. (2024). Novel genetic variants associated with primary myocardial fibrosis in sudden cardiac death victims. Journal of Cardiovascular Translational Research, 17(6), 1229–1239. https://doi.org/10.1007/s12265-024-10527-5 https://doi.org/10.1007/s12265-024-10527-5 Rinnakkaistallennettu versio Doedens, A., Skarp, S., Mattila, O., Laasonen, S., Huikuri, H. V., Junttila, J., & Kerkelä, R. (2026). The role of OMA1 and UNC45A in primary myocardial fibrosis. Manuscript in preparation. Doedens, A., Skarp, S., Holmström, L., Pakanen, L., Saarimäki, S., Kerkelä, R., Pylkäs, K., Huikuri, H. V., & Junttila, J. (2025). Genetic variants associated with cardiac hypertrophy-related sudden cardiac death and cardiovascular outcomes in a Finnish population. Heart, 111(2), 55–61. https://doi.org/10.1136/heartjnl-2024-324623 https://doi.org/10.1136/heartjnl-2024-324623 Academic dissertation to be presented with the assent of the Doctoral Programme Committee of Health and Biosciences of the University of Oulu for public defence in Auditorium F202 of the Faculty of Medicine (Aapistie 5 B), on 27 February 2026, at 12 noonAbstract
Sudden cardiac death (SCD) is a common mode of death leading to 15 to 20 percent of all mortalities. Up to one fifth of all SCDs are caused by nonischaemic myocardial diseases, and in many of these victims previously diagnosed cardiac conditions are absent. One major shared feature among these individuals is myocardial fibrosis, i.e., fibrotic tissue build-up in the myocardium. This pathological condition can cause arrhythmias and cardiac failure. The aim of this doctoral project was to identify genetic variants predisposing to myocardial fibrosis and SCD and to investigate the function of the identified candidate genes in vitro.
We analysed the genetic background of SCD victims who had either primary myocardial fibrosis (PMF, N = 127) or hypertension-related cardiac hypertrophy (N = 96). All victims were part of the Finnish Genetic Study for Arrhythmic events (FinGesture) which has collected tissue samples and clinical information of approximately 6,000 SCD victims since 1998. Associations of the identified variants with cardiac diseases in Finnish population were investigated in the FinnGen dataset.
Fifty-seven candidate genes were identified, many belonging to pathways contributing to cardiomyocyte survival and extracellular matrix organization. These included Unc-45 myosin chaperone (UNC45A) and OMA1 zinc metallopeptidase (OMA1). Transcriptional changes associated with PMF were identified using 3’mRNA sequencing of heart samples. mRNA sequencing revealed that transcriptomic changes in PMF occur, among others, in genes participating in actin cytoskeleton organization and muscle structure development. UNC45A was upregulated in PMF compared to controls. Knockdown of OMA1 in fibroblasts resulted in increased cell proliferation and collagen production. Knockdown of UNC45A in fibroblasts decreased cell proliferation and collagen production.
In conclusion, the possible role of the identified genes in myocardial fibrosis may facilitate the diagnosis and prevention of myocardial fibrosis and decrease the risk of SCD in persons showing symptoms and their family members.Tiivistelmä
Sydänperäinen äkkikuolema on yleinen kuolinsyy, joka aiheuttaa 15–20 % kaikista kuolemista. Noin viidesosa kaikista tapauksista johtuu muista kuin iskeemisistä sydänsairauksista, ja monilla ei ole aiemmin diagnosoituja sydänsairauksia. Yksi merkittävä yhteinen piirre sydänperäisillä äkkikuolematapauksilla on sydänlihaksen fibroosi eli sidekudoksen kertyminen sydänlihakseen, mikä voi aiheuttaa rytmihäiriöitä ja sydämen vajaatoimintaa. Tämän väitöskirjatyön tavoitteena oli tunnistaa geneettisiä variantteja, jotka altistavat sydänlihaksen fibroosille, sekä tutkia tunnistettujen kandidaattigeenien toimintaa solumalleissa.
Tutkimusaineisto koostuu äkkikuolematapauksista, joilla ruumiinavauksessa todettiin joko primaari sydänlihasfibroosi (N = 127) tai sydänlihasfibroosi sekä sydämen hypertrofia (N = 96). Kaikki tapaukset olivat osa FinGesture-tutkimusta, jossa on kerätty kudosnäytteitä ja kliinistä tietoa äkkikuolematapauksista vuodesta 1998 lähtien. Tunnistettujen varianttien assosiaatiota sydänsairauksiin suomalaisessa väestössä tutkittiin FinnGen-aineistossa. Tunnistimme yhteensä 57 kandidaattigeeniä, joista monet osallistuvat kardiomyosyyttien selviytymiseen ja soluväliaineen järjestäytymiseen vaikuttaviin signalointireitteihin. Tunnistetuista kandidaattigeeneistä tarkastelimme solukokeissa Unc-45 myosiinichaperonis (UNC45A) ja OMA1 sinkkimetallopeptidaasis (OMA1) toimintaa.
Sydänlihasfibroosiin liittyviä transkriptionaalisia muutoksia tunnistettiin sydännäytteiden 3’mRNA-sekvensoinnin avulla. Transkriptionaalisia muutoksia havaittiin muun muassa aktiinisytoskeletonin järjestäytymiseen ja lihasrakenteen kehitykseen osallistuvissa signalointireiteissä. UNC45A-geenin ekspressiotaso oli korkeampi fibroottisissa sydämissä verrattuna kontrolleihin. OMA1-geenin hiljentäminen lisäsi fibroblastien jakautumista ja kollageenin tuotantoa. UNC45A:n hiljentäminen fibroblasteissa puolestaan vähensi solujen jakaantumista ja kollageenin tuotantoa.
Yhteenvetona voidaan todeta, että tunnistettujen geenien mahdollinen rooli sydänlihaksen fibroosissa voi helpottaa sen diagnosointia ja ennaltaehkäisyä sekä vähentää äkkikuoleman riskiä oireita osoittavilla henkilöillä ja heidän perheenjäsenillään
Het 25e B.I.L. -bestuur presenteert
No full textBij een nieuw collegejaar hoort een nieuw B.I.L.-bestuur. Om het nieuwe bestuur alvast een beetje te leren kennen presenteert het 25e B.I.L.-bestuur met trots het 26e B.I.L. -bestuur. Maak kennis met: Elise van Zeeland, Charlotte Wagenaar, Vanesa Berisha, Hanna Blomaard, Janna Cheretis, Meike Arets en Lisanne Doedens
Increasing αvβ3 selectivity of the anti-angiogenic drug cilengitide by N-methylation
No full textA subtle change: Structural changes upon amide bond methylation improve the selectivity of the anti-angiogenic drug Cilengitide, which after N-methylation at distinct positions discriminates between the closely related pro-angiogenic integrins αvβ3 and αvβ5 (see scheme). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
On Biblical Hebrew and Computer Science: Inspiration, Models, Tools, And Cross-fertilization
No full textEep Talstra's work has been an inspiration to maby researchers, both within and outside of the field of Old Testament scholarship. Among others, Crist-Jan Doedens and the present author have been heavily influenced by Talstra in their own work within the field of computer science. The present article describes som f the ways in which Talstra's work has influenced the work of Doedens and the present author, and som of the outcomes that have sprung of Doedens are described, including their decendants, the EMdF model and the MQL query language as implemented in the Emdros corpus query system of the present author. In addition, the tools surrounding Emdros, including SESB, Libronis, and the Emdros Query Tool, are described. Ecamples Biblical Hebrew scholar. Thus the inspiration of Talstra comes full-circle: from Biblical Hebrew databases to computer science and back into Biblical Hebrew scholarship
Optimal CO? pressure for 'stand alone' pneumatic systems
No full textCO2 powered actuators are a viable alternative in prostheses and robotics. The gas supply is generally limited in such applications, and calls for an optimal system pressure to minimize gas-consumption. Previous work which discusses the optimal pressure was not verifiable, or strictly theoretical. The theoretical work was unintuitive, but did result in an optimal pressure level of 1.2 MPa, irrespective of the required output force. This research presents a simplified theoretical background, and verifies the optimum by measurements. The simplified theory offers improved insight into the existence of an optimal supply pressure and locates it at 1.42 MPa. Compensation for atmospheric pressure strongly affects cylinder size at low system pressures and above the optimum, as CO2 approaches its critical point, gas consumption increases with the density of the gas. The experiments show an optimum at 1.12 MPa, with a bound of -0.10 MPa and +0.30 MPa. The uncertainty in the location of the minimum gas-consumption reflects the challenges of accurately performing the measurements, as well as the shallow curve where the minimum is found. The presented results support the optimal supply pressure found in literature, and when optimizing a pneumatic system for CO2 use, 1.2 MPa is therefore a good choice.BMDBioMechanical EngineeringMechanical, Maritime and Materials Engineerin
Use of latex in natural fibre reinforced plastics
No full textPolymers and composite materials have replaced many conventional materials (wood, metals, natural fibres) in the past decades. Cost reduction, productivity increase, weight saving and better mechanical properties are the main reasons for this development. In recent years however, there is a renewed interest in natural fibres, especially as reinforcement in composite materials. Main reasons for this is an increased awareness of our environment. Typical subjects in this respect are ‘reduction of CO2 emissions’, ‘recycling’ and ‘protection of resources’. The automotive industry was the first to use natural fibres on a larger scale, not only because of environmental advantages but also because of cost- and weight reduction. Several cars produced or even used at this very moment, contain a considerable amount of natural fibres. This report investigates the possibilities of natural fibres as reinforcement in thermoplastic composites. It focuses on the problems of natural fibre prepreg production and brings up latex processing as a possible solution to some of these problems…Applied SciencesAerospace EngineeringStructures and Materials Laborator
An overlooked dicopper(I) helicate
No full textDepartment of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata-700 032, India
Manuscript received 17 March 2003, accepted 22 August 2003
It is pointed out that [Cu2(L)2(LH)2] where LH Ph-N=N-C(Me)=N-OH, is the first structurally characterised [M. H. Dickman and R. J. Doedens, lnorg. Chem., 1980, 19, 3112] double stranded helicate where metal coordination and H-bonding work in tandem to bring about a helical topology
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Role of myeloid Hypoxia-Inducible Factor-1alpha in the tumor microenvironment
No full textSolid tumors are frequently infiltrated by large numbers of non-cancerous hematopoietic cells, including macrophages. The pro-tumor or anti-tumor role of macrophages in the tumor microenvironment is unclear. Tumors are also characterized by regions of low oxygen tension. Mammalian cells respond transcriptionally to low oxygen tension via the Hypoxia-Inducible Factor-1alpha, which upregulates genes involved in glycolysis, angiogenesis, and cell survival. Previous work has shown that myeloid cells deficient for HIF-1alpha are impaired in their inflammatory responses. To genetically test the role of the myeloid hypoxic response mediated by HIF- 1alpha in the tumor microenvironment, we used the loxP/ tissue specifc cre recombianse to generate murine myeloid specific deletion of HIF-1alpha in rodents with an established transgenic model of breast cancer, MMTV-PyMT. Lack of HIF-1alpha in the tumor microenvironment resulted in tumors with less mass, but with increased cell death. Enzyme activities of iNOS and ArgI were reduced in whole tumor lysates. In vitro experiments demonstrated HIF-1 alpha, not HIF-2alpha, control of L-arginine degrading enzymes iNOS and arginase I. Further characterization of the relationship between macrophages and tumor cells using co-culture strategies revealed that tumor cells induce ArgI in a HIF-1alpha and hypoxia dependent fashion at the protein level. iNOS was detected at the RNA level after co -culture with MECs, but was scarcely detectable at the protein level. ArgI and iNOS have been implicated in T cell immunosuppression. PyMT tumor bearing mice displayed evidence of T cell activation, yet T cells isolated from myeloid HIF WT tumors were less responsive than those from myeloid HIF KO tumors after stimulation with CD3/28 ex vivo. We propose myeloid HIF-1alpha contributes to local tumor immunosuppression of T cell function. This suggests inhibition of HIF-1 may have beneficial effects not only by blocking tumor growth and survival under hypoxia, but also by relieving myeloid cell mediated immunosuppression in the tumor microenvironmen
Aan de slag met afasie
No full textItem does not contain fulltextMensen met afasie na hersenletsel hebben baat bij een benadering die verder gaat dan het behandelen van de stoornis alleen. Het uitgangspunt voor de logopedist moet liggen bij hun mogelijkheden om deel te nemen aan het dagelijks leven en de maatschappij. Daarom staat in Aan de slag met afasie communicatieve participatie centraal.
In het boek is de levensloop van een persoon met afasie de rode draad. Van acute zorg tot het opnieuw vinden van balans in het dagelijks leven: elk hoofdstuk geeft inzicht in de rol van de logopedist in de verschillende fasen van herstel. Deze holistische benadering benadrukt niet alleen de communicatie, maar ook het omgaan met levend verlies; een belangrijk aspect waar veel mensen met hersenletsel en hun omgeving mee te maken krijgen.
Naast een theoretisch kader biedt dit boek een duidelijke focus op klinisch redeneren. Het helpt om theorie en praktijk samen te brengen, ondersteund door realistische casussen en praktische voorbeelden. Dankzij de bijdragen van ervaringsdeskundigen en studenten is het boek herkenbaar en direct toepasbaar in de praktijk.
Voor wie
Aan de slag met afasie is een praktische en toegankelijke gids voor aankomende en ervaren logopedisten die hun vak willen verdiepen en zowel de praktische als emotionele kant ervan willen begrijpen
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