Estrogens and genomic instability in human cancer cells-involvement of Src/Raf/Erk signaling in micronucleus formation by estrogenic chemicals

This article is available open access through the publisher’s website. Copyright @ 2008 The Authors.Reports of the ability of estrogenic agents such as 17β-estradiol (E2), estriol (E3) and bisphenol A (BPA) to induce micronuclei (MN) in MCF-7 breast cancer cells have prompted us to investigate whether these effects are linked to activation of the estrogen receptor (ER) α. Coadministration of tamoxifen and the pure ER antagonist ICI 182 780 to cells treated with E2 and E3 did not lead to significant reductions in micronucleus frequencies. Since these antiestrogens interfere with the transcriptional activity of the ER and block promotion of ER-dependent gene expression, it appears that this process is not involved in micronucleus formation. However, ER activation also triggers rapid signaling via the Src/Raf/extracellular signal-regulated kinase (Erk) pathway. When MCF-7 cells were exposed to E2 and BPA in combination with the specific kinase inhibitors pyrazolopyrimidine and 2′-amino-3′-methoxyflavone, reductions in micronucleus frequencies occurred. These findings suggest that the Src/Raf/Erk pathway plays a role in micronucleus formation by estrogenic agents. Enhanced activation of the Src/Raf/Erk cascade disturbs the localization of Aurora B kinase to kinetochores, leading to a defective spindle checkpoint with chromosome malsegregation. Using antikinetochore CREST antibody staining, a high proportion of micronucleus containing kinetochores was observed, indicating that such processes are relevant to the induction of MN by estrogens. Our results suggest that estrogens induce MN by causing improper chromosome segregation, possibly by interfering with kinase signaling that controls the spindle checkpoint, or by inducing centrosome amplification. Our findings may have some relevance in explaining the effects of estrogens in the later stages of breast carcinogenesis.European Commissio

A critical analysis of the autonomy of art in Finnish cultural policy 1978-2011

The use of art for the purpose of attaining extra-artistic aims has increased during the last decades. Moreover, discourses of economic origin have entered the artistic realm bringing forth increasing instrumentalist objectives. Art is prompted to constantly justify its existence. Measurable results, evidence of benefits and requirements of efficacy become naturalized features of the field of art. This study seeks to explore what is happening to the autonomy of art in this course of development? Within a critical framework the aim of this study is to examine the autonomy vis-à-vis the instrumentalism in terms of Finnish cultural policy from 1978 to 2011. The analysis is conducted with data consisting of cultural policy reports from 1978, 1993 and 2011. Critical theory and particularly theories concerning the autonomy of art developed by Theodor W. Adorno constitute the theoretical framework of the study. As its methodology, this study adopts a qualitative and interdisciplinary research approach, deploying both content and critical discourse analysis. Further, in the spirit of a critical and reflexive research orientation, this study seeks to examine latent phenomena and structures that without thorough examination may remain uncovered. The findings entail that instrumentalism has been a salient feature of Finnish cultural policy since the late 1970s. However, the forms of instrumentalism have been subject to change. The societal instrumentalism of the 1970s has evolved into increasing economic forms of instrumentalism when moving towards the 21st century. The effects of these different instrumentalist developments have varied in terms of the autonomy of art. One of the central arguments of this study is that the increasing economic forms of instrumentalism are mainly a result of neo-liberalism. As a societal ideology starting to prevail in the 1990s, neo-liberalism has influenced cultural policy to a direction that puts increased emphasis on the economic and social benefits of art, making the approach towards art almost exclusively instrumental. This study claims that even though cultural policy has always been instrumental in its relationship towards art, the forms of instrumentalism that has emerged during the late 20th century are to a wider extent than before a threat to the autonomy of art

Safety Aspects of Bio-Based Nanomaterials

Moving towards a bio-based and circular economy implies a major focus on the responsible and sustainable utilization of bio-resources. The emergence of nanotechnology has opened multiple possibilities, not only in the existing industrial sectors, but also for completely novel applications of nanoscale bio-materials, the commercial exploitation of which has only begun during the last few years. Bio-based materials are often assumed not to be toxic. However, this pre-assumption is not necessarily true. Here, we provide a short overview on health and environmental aspects associated with bio-based nanomaterials, and on the relevant regulatory requirements. We also discuss testing strategies that may be used for screening purposes at pre-commercial stages. Although the tests presently used to reveal hazards are still evolving, regarding modifi­cations required for nanomaterials, their application is needed before the upscaling or commercialization of bio-based nanomaterials, to ensure the market potential of the nanomaterials is not delayed by uncertainties about safety issues

The integrity of the U12 snRNA 3 ' stem-loop is necessary for its overall stability

Disruption of minor spliceosome functions underlies several genetic diseases with mutations in the minor spliceosome-specific small nuclear RNAs (snRNAs) and proteins. Here, we define the molecular outcome of the U12 snRNA mutation (84C>U) resulting in an early-onset form of cerebellar ataxia. To understand the molecular consequences of the U12 snRNA mutation, we created cell lines harboring the 84C>T mutation in the U12 snRNA gene (RNU12). We show that the 84C>U mutation leads to accelerated decay of the snRNA, resulting in significantly reduced steady-state U12 snRNA levels. Additionally, the mutation leads to accumulation of 3 '-truncated forms of U12 snRNA, which have undergone the cytoplasmic steps of snRNP biogenesis. Our data suggests that the 84C>U-mutant snRNA is targeted for decay following reimport into the nucleus, and that the U12 snRNA fragments are decay intermediates that result from the stalling of a 3 '-to-5 ' exonuclease. Finally, we show that several other single-nucleotide variants in the 3 ' stem-loop of U12 snRNA that are segregating in the human population are also highly destabilizing. This suggests that the 3 ' stem-loop is important for the overall stability of the U12 snRNA and that additional disease-causing mutations are likely to exist in this region.Peer reviewe

Nulägeskartläggning med Value Stream Mapping

Examensarbetet handlar om att utföra en nulägeskartläggning av produktionsprocessen för PMM generatorer inom marinsektorn vid företaget The Switch. Genom att skapa en nuläges Value Stream Map, kan man ge en överblick av produktionen för företagsledningen samt identifiera ineffektivitet som kan förebyggas i framtiden. Syftet med examensarbetet var att analysera och kartlägga produktionsflödet för att identifiera ineffektivitet med hjälp av Value Stream Mapping och principer från Lean tänkande. I teorin beskrivs hur en Value Stream Mapping utförs och vilka delsteg metoden består av. Förutom Value Stream Mapping förklaras Lean samt Lean metoder som anses vara nödvändiga för en fungerande produktionsprocess. I teorin fördjupas det även i vad ineffektivitet och flaskhalsar innebär och hur dessa kan förebyggas med olika metoder. Arbetet utfördes i huvudsak genom att använda en blankett som de anställda på företaget fyllde i och genom det var delaktiga i arbetet. Till arbetet ingick även analys av de olika arbetsskedena med uppdragsgivaren, samt granskning av monteringsinstruktioner och utförande av korta intervjuer med sakkunniga i produktionen. Resultatet från arbetet är två Value Stream Map över två PMM generatorer som producerats under cirka åtta veckors tidsintervall. Kartorna illustrerar värdeskapande information från produktionsprocessen och kan användas som mall även i framtiden. Kartorna ger även företagsledningen information om tidsåtgången i de olika arbetsskeden.Opinnäytetyön aiheena on PMM generaattoreiden tuotantoprosessin nykytilan kartoitus merenkulkualalla The Switch yrityksessä. Luomalla nykyinen arvovirtakartta, pystytään antamaan yleiskuva tuotannosta yrityksen johdolle ja löytämään tehottomuuksia, jotka voidaan ehkäistä tulevaisuudessa. Opinnäytetyön tarkoituksena oli analysoida ja kartoittaa tuotantovirta tehottomuuden tunnistamiseksi arvovirtakartoituksen ja Lean-ajattelun periaatteiden avulla. Teoriassa kuvataan, miten arvovirtakartoitus suoritetaan ja mistä osavaiheista menetelmä koostuu. Arvovirtakartoituksen lisäksi perehdytään Lean ajatteluun ja Lean menetelmiin, joita pidetään tarpeellisina toimivan tuotantoprosessin kannalta. Teoriassa syvennytään myös siihen, mitä tehottomuus ja pullonkaulat tarkoittavat ja miten niitä voidaan ehkäistä eri menetelmillä. Työssä käytettiin pääasiassa itse laadittua lomaketta, jonka yrityksen työntekijät täyttivät ja olivat sitä kautta mukana työssä. Työhön kuului myös tuotantoon perehtymistä analysoimalla eri työvaiheita toimeksiantajan kanssa, sekä käymällä läpi kokoonpano ohjeita ja haastattelemalla lyhyesti tuotannon asiantuntijoita. Opinnäytetyön tuloksena on kaksi arvovirtakarttaa, jotka tuotettiin noin kahdeksan viikon aikana kahdesta PMM generaattorista. Kartat havainnollistavat tuotantoprosessista saatavaa lisäarvotietoa, ja niitä voidaan käyttää mallina tulevaisuudessa. Kartat antavat myös yrityksen johdolle tietoa eri työvaiheisiin käytetystä ajasta.The thesis is about performing a current mapping of the production process for PMM generators in the marine sector at the company The Switch. By creating a current Value Stream Map, be able to provide an overview of the production for company management and identify inefficiencies that can be prevented in the future. The purpose of the thesis was to analyse and map the production flow to identify inefficiencies using Value Stream Mapping and principles from Lean thinking. The theory describes how a Value Stream Mapping is performed and what sub steps the method consists of. In addition to Value Stream Mapping, Lean and Lean methods that are considered necessary for a functioning production process are explained. The theory also delves into what inefficiency and bottlenecks mean and how these can be prevented with different methods. The work was mainly carried out using a self-made form that the company's employees filled out, and they were involved in the process. The work also included familiarisation with the production by analysing the various work stages with the client, as well as reviewing the assembly instructions and conducting short interviews with experts in production. The result of the work is two Value Stream Maps of two PMM generators produced over a period of about eight weeks. The maps illustrate value creating information from the production process and can be used as a template in the future. The maps also provide the company management with information regarding the time spent in different work stages

Liiketoimintasuunnitelma : Yritys X Oy

Opinnäytetyössä laadittiin liiketoimintasuunnitelma perustettavalle Yritys X Oy:lle, jonka toiminta keskittyy ensiapukurssien ja ensiapuvälineiden myyntiin Pyhätunturin alueen matkailualan yrityksille. Opinnäytetyön tavoitteena oli kartoittaa liiketoimintamahdollisuuksia ja luoda vankka suunnitelma yrityksen menestymiselle. Työssä tutkittiin markkina-aluetta, arvioitiin potentiaalisten asiakkaiden määrää ja analysoitiin yhteiskunnallisia tekijöitä, jotka voivat vaikuttaa yrityksen toimintaan PESTEL-analyysin avulla. Teoriaosuudessa perehdyttiin liikeidean ja liiketoimintasuunnitelman laatimiseen tarvittaviin menetelmiin sekä käytettiin PESTEL-, Porterin viiden kilpailuvoiman mallia ja SWOT-analyysia syvällisen liiketoimintakuvan saamiseksi. Tutkimuksen tulokset osoittivat, että Yritys X Oy:lla on hyvät edellytykset kannattavaan toimintaan alueellaan