185 research outputs found

    War and Revolution in St. Petersburg : Modernist Links in the Poetry of Edith Södergran and Anna Andreevna Akhmatova

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    Important modernists in their own countries, Anna Akhmatova and Edith Södergran are compared in this dissertation as poets whose poetry reflects the climactic events of the early twentieth century in Finland and Russia. A comparatist, biographical and historical approach is used to uncover the circumstances surrounding these events. First the poets’ early works are reviewed and their contemporaries are mentioned to provide a poetic context. Then a brief review of Finnish and Russian history situates them historically. Next, the rich literary diversity of St. Petersburg’s Silver Age is presented and the work of the poets is viewed in context before their poetry is compared, as the First World War, October Revolution and subsequent Finnish Civil War impact their writing. While biography is not the primary focus, it becomes important as inevitably the writers’ lives are changed by cataclysmic events and the textual analysis of the poems in Swedish, Russian and English shows the impact of war on their poetry. These two poets have not been compared before in a critical review in English and this work contributes to needed work in English. They share certain common modernist traits: attention to the word, an intimate, unconventional voice, and a concern with audience. In addition, they both reject formal traditions while they adopt new forms and use modern, outside influences such as art, architecture and philosophy as subject matter and a lens through which to focus their poetry. While it may seem that Anna Akhmatova was the most socially aware poet, because of the censorship she endured under Stalin, my research has revealed that actually Edith Södergran showed the most social consciousness. Thus, a contrast of the poets’ themes reveals these differences in their approaches. Both poets articulated a vibrant response to war and revolution becoming modernists in the process. In their final works created in the years before their deaths, they reveal the solace they found in nature as well as final mentions of the violent events of their youth. Keywords: St. Petersburg, Modernism, Symbolism, Acmeism, Silver Age, Finland-Swedish literatureOmien maidensa merkittäviä modernisteja Anna Ahmatovaa ja Edith Södergrania verrataan tässä väitöskirjassa runoilijoina, joiden tuotanto heijastaa 1900-luvun alun käänteentekeviä muutoksia Suomessa ja Venäjällä. Käytetty vertaileva elämäkerrallinen ja historiallinen lähestymistapa paljastaa olosuhteet, jotka olivat näiden tapahtumien taustalla. Aluksi tarkastellaan runoilijoiden varhaistuotantoa ja yleiskuvan aikaansaamiseksi mainitaan muita heidän ikäpolvensa runoilijoita. Lyhyt katsaus Suomen ja Venäjän historiaan peilaa heitä omaa aikaansa vasten. Seuraavaksi esitellään Pietarin hopea-ajan rikas kirjallinen monimuotoisuus, jonka valossa runoilijoiden tuotantoa tarkastellaan, ennen kuin heidän runouttaan verrataan toisiinsa ensimmäisen maailmansodan, lokakuun vallankumouksen ja Suomen sisällissodan taustaa vasten. Vaikka elämäkertaan keskittyminen ei ole ensisijasta, se on tärkeää, koska mullistavat tapahtumat muuttivat väistämättömästi kirjailijoiden elämän. Sodan vaikutus heidän runouteensa tulee esiin runojen tekstianalyysissä. Näitä kahta runoilijaa ei ole aiemmin verrattu kriittisesti englannin kielellä, ja siksi tämä työ pyrkii osaltaan täyttämään englanninkielisen teoksen puutteen. Runoilijoilla on tiettyjä yhteisiä, modernisteille tyypillisiä piirteitä: sanojen pohtiminen, intiimi, epäsovinnainnen ilmaisu ja lukijoiden mielessä pitäminen. Lisäksi he molemmat hylkäävät muodolliset perinteet samalla kun omaksuvat uusia ilmaisumuotoja ja käyttävät moderneja ulkopuolisia vaikutteita, kuten taidetta, arkkitehtuuria ja filosofiaa aiheinaan ja linssinä, jonka polttopisteessä heidän runoutensa tarkentuu. Vaikka Anna Ahmatova saattaa näyttää näistä kahdesta yhteiskuntatietoisemmalta runoilijalta, koska hän joutui sietämään Stalinin sensuuria, tämä tutkimus paljastaa, että todellisuudessa Edith Södergran osoitti suurempaa yhteiskuntatietoisuutta. Runoilijoiden aiheiden vastakohtaisuus osoittaa nämä erot heidän lähestymistavoissaan. Molemmat runoilijat ilmaisevat selkeästi voimakkaan reaktionsa sotaan ja vallankumoukseen ja tulivat modernisteiksi niiden pyörteissä. Viimeisissä kuolinvuosia edeltävissä teoksissaan he puhuvat lohdusta, jonka he ovat löytäneet luonnosta. Samoin he vielä kerran palaavat nuoruutensa väkivaltaisiin tapahtumiin. Avainsanat: Pietari, modernismi, symbolismi, akmeismi, hopea-aika, suomenruotsalainen kirjallisuusKrig och revolution i S:t Petersburg: Modernistiska likheter i Edith Södergrans och Anna Andreevna Akhmatovas poesi De framträdande modernisterna Edith Södergran och Anna Akhmatova skrev båda en poesi som återspeglar händelserna i Finland och Ryssland under början av 1900-talet. Denna avhandling granskar likheterna ur ett komparativt, biografiskt och historiskt perspektiv. Först presenteras poeternas tidigaste verk med samtida diktare som litterär kontext, och sedan ges en kort översikt av Finlands och Rysslands historia som historisk bakgrund. Därefter presenteras den rika litteraturen under den s.k. silveråldern i S:t Petersburg som inramar Södergrans och Akhmatovas dikter i tiden. Slutligen görs en jämförelse av hur deras poesi påverkades av första världskriget, oktoberrevolutionen och det finska inbördeskriget. Trots att fokus inte ligger på biografierna har de en betydelse eftersom de våldsamma händelserna oundvikligen påverkade författarnas liv. Analysen av texterna på svenska, ryska och engelska visar hur de dramatiska upplevelserna återspeglas i deras poesi. De två poeterna har aldrig tidigare jämförts i en kritisk översikt på engelska, och avhandlingen bidrar till att fylla behovet av engelskspråkig forskning om deras poesi. De uppvisar gemensamma drag inom modernismen; båda fokuserar på orden och är lyhörda, de använder ett nyskapande språk och talar till läsarna med en intim och okonventionell röst. Båda tar också avstånd från formaliteter och traditioner; de skapar nya uttrycksformer och använder konst, arkitektur och filosofi som teman i sina dikter och speglar sin poesi genom dem. Anna Akhmatovas dikter blev hårt censurerade under Stalins tid och man kunde tro att hon är den mer socialt medvetna poeten av de två, men min forskning har visat att Edith Södergran faktiskt hade ett större socialt medvetande. Jämförelsen av tematiken i deras dikter visar hur olika författarna närmar sig ämnet. Båda reagerar starkt mot kriget och revolutionen genom att ty sig till modernismen. De sista dikterna strax före författarnas död handlar om den tröst de finner i naturen och om de våldsamma upplevelserna under ungdomstiden. Nyckelord: S:t Petersburg, modernism, symbolism, akmeism, silveråldern, finlandssvensk litteraturАбстракт: Война и революция в Санкт-Петербурге: переклички в модернистской поэзии Эдит Сëдергран и Анны Ахматовой В данной диссертации видные представители модернистской поэзии России и Финляндии, Анна Ахматова и Эдит Сëдергранд, сравниваются как поэтессы, в творчестве которых отразились эпохальные события начала ХХ века. Для раскрытия обстоятельств этих событий используются сравнительный, биографический и исторический подходы. Сначала ранние работы поэтесс оцениваются на фоне поэтического контекста того периода. Затем эти работы рассматриваются в контексте исторической ситуации в Финляндии и России. Описывается богатое литературное разнообразие Серебряного века в Санкт-Петербурге и поэзия обоих авторов в этом контексте с целью выяснения влияния, оказанного на творчество поэтесс Первой Мировой войной, Октябрьской революцией и Гражданской войной. Хотя биографические данные не являются целью анализа, нельзя отрицать того, что исторические катаклизмы не могли не повлиять на судьбу поэтесс, что подтверждается анализом стихов на шведском, русском и английских языках. Ранее эти две поэтессы в англоязычной критике никогда не сравнивались, и данная работа восполняет этот пробел. Есть много общего в творчестве обеих авторов: внимание к слову, интимная и нестандартная интонация, уважение к читателю. Кроме этого, обе поэтессы, отвергая формалистские традиции, используют новые формы и влияния, навеянные искусством, архитектурой и философией, и в качестве тематики стихов, и в качестве угла зрения на свое творчество. На первый взгляд, Ахматова может считаться более социально-ориентированным поэтом, потому что она пережила цензуру при Сталине, но исследование выявило, что поэзия Эдит Сëдергран оказалась гораздо более социально-направленной. Различие в подходах авторов выявляет, например, сопоставление тематики, хотя обе поэтессы эмоционально откликнулись на войну и революцию, что предопределило их становление в поэзии как модернистов. В стихах последних лет жизни оба автора нашли утешение в природе и в воспоминаниях о бурных событиях своей юности. Ключевые слова: Санкт-Петербург, модернизм, акмеизм, символизм, Серебряный век, финско-шведская литератур

    Exploratory study of functional and psychological factors associated with employment status in patients with head and neck cancer

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    Background Compared with other malignancies, head and neck cancer (HNC) increases the risk of not returning to work (RTW). Methods Within a cross-sectional study, patients with HNC filled out the OncoFunction questionnaire, a version of the International Classification of Functioning Core Sets for HNC. In 231 patients below 65 years of age, associations of sociodemographic, clinical, functional, and psychological factors with employment and participation in rehabilitation program were explored. Results Unemployed patients reported more swallowing difficulties and speaking problems. Being unemployed was associated with higher levels of depressive and anxiety symptoms, fatigue, and lower global health. Rehabilitation participation was not significantly associated with any of the assessed factors except for smoking. Conclusions Unemployed patients with HNC are more burdened than employed patients with HNC regarding clinical, psychological, and functional factors. These differences are more evident later in recovery. Rehabilitation participation was not associated with psychological and functional burden which indicates the need for tailored HNC rehabilitation programs

    Deregulated splicing is a major mechanism of RNA-induced toxicity in Huntington's disease

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    Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin (HTT) gene, translating into an elongated polyglutamine stretch. In addition to the neurotoxic mutant HTT protein, the mutant CAG repeat RNA can exert toxic functions by trapping RNA-binding proteins. While few examples of proteins that aberrantly bind to mutant HTT RNA and execute abnormal function in conjunction with the CAG repeat RNA have been described, an unbiased approach to identify the interactome of mutant HTT RNA is missing. Here, we describe the analysis of proteins that preferentially bind mutant HTT RNA using a mass spectrometry approach. We show that (I) the majority of proteins captured by mutant HTT RNA belong to the spliceosome pathway, (II) expression of mutant CAG repeat RNA induces mis-splicing in a HD cell model, (III) overexpression of one of the splice factors trapped by mutant HTT ameliorates the HD phenotype in a fly model and (VI) deregulated splicing occurs in human HD brain. Our data suggest that deregulated splicing is a prominent mechanism of RNA-induced toxicity in HD

    M1-linked ubiquitination by LUBEL is required for inflammatory responses to oral infection in Drosophila

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    Post-translational modifications such as ubiquitination play a key role in regulation of inflammatory nuclear factor-κB (NF-κB) signalling. The Drosophila IκB kinase γ (IKKγ) Kenny is a central regulator of the Drosophila Imd pathway responsible for activation of the NF-κB Relish. We found the Drosophila E3 ligase and HOIL-1L interacting protein (HOIP) orthologue linear ubiquitin E3 ligase (LUBEL) to catalyse formation of M1-linked linear ubiquitin (M1-Ub) chains in flies in a signal-dependent manner upon bacterial infection. Upon activation of the Imd pathway, LUBEL modifies Kenny with M1-Ub chains. Interestingly, the LUBEL-mediated M1-Ub chains seem to be targeted both directly to Kenny and to K63-linked ubiquitin chains conjugated to Kenny by DIAP2. This suggests that DIAP2 and LUBEL work together to promote Kenny-mediated activation of Relish. We found LUBEL-mediated M1-Ub chain formation to be required for flies to survive oral infection with Gram-negative bacteria, for activation of Relish-mediated expression of antimicrobial peptide genes and for pathogen clearance during oral infection. Interestingly, LUBEL is not required for mounting an immune response against systemic infection, as Relish-mediated antimicrobial peptide genes can be expressed in the absence of LUBEL during septic injury. Finally, transgenic induction of LUBEL-mediated M1-Ub drives expression of antimicrobial peptide genes and hyperplasia in the midgut in the absence of infection. This suggests that M1-Ub chains are important for Imd signalling and immune responses in the intestinal epithelia, and that enhanced M1-Ub chain formation is able to drive chronic intestinal inflammation in flies

    Trim17, novel E3 ubiquitin-ligase, initiates neuronal apoptosis

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    Accumulating data indicate that the ubiquitin-proteasome system controls apoptosis by regulating the level and the function of key regulatory proteins. In this study, we identified Trim17, a member of the TRIM/RBCC protein family, as one of the critical E3 ubiquitin ligases involved in the control of neuronal apoptosis upstream of mitochondria. We show that expression of Trim17 is increased both at the mRNA and protein level in several in vitro models of transcription-dependent neuronal apoptosis. Expression of Trim17 is controlled by the PI3K/Akt/GSK3 pathway in cerebellar granule neurons (CGN). Moreover, the Trim17 protein is expressed in vivo, in apoptotic neurons that naturally die during post-natal cerebellar development. Overexpression of active Trim17 in primary CGN was sufficient to induce the intrinsic pathway of apoptosis in survival conditions. This pro-apoptotic effect was abolished in Bax(-/-) neurons and depended on the E3 activity of Trim17 conferred by its RING domain. Furthermore, knock-down of endogenous Trim17 and overexpression of dominant-negative mutants of Trim17 blocked trophic factor withdrawal-induced apoptosis both in CGN and in sympathetic neurons. Collectively, our data are the first to assign a cellular function to Trim17 by showing that its E3 activity is both necessary and sufficient for the initiation of neuronal apoptosis. Cell Death and Differentiation (2010) 17, 1928-1941; doi: 10.1038/cdd.2010.73; published online 18 June 201

    Regulation of HSP27 on NF-κB pathway activation may be involved in metastatic hepatocellular carcinoma cells apoptosis

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    <p>Abstract</p> <p>Background</p> <p>During the process of metastasis, cells are subjected to various apoptotic stimuli. Aberrant expression of apoptotic regulators often contribute to cell metastasis. Heat shock protein 27(HSP27) is confirmed as an apoptosis regulator, but its antiapoptotic mechanism in metastatic hepatocellular carcinoma (HCC) cells remains unclear.</p> <p>Methods</p> <p>Levels of HSP27 protein and its phosphorylation in Hep3B, MHCC97L to MHCC97H cells with different metastatic potentials were determined by western blot analysis. MHCC97H cells were transfected with specific small interference RNA (siRNA) against HSP27. The <it>in vitro </it>migration and invasion potentials of cells were evaluated by Transwell assay. The apoptosis ratio of MHCC97H cells was analyzed by TUNEL staining and Flow Cytometry. Alteration of signal transduction pathway after HSP27 knockdown in MHCC97H cells was evaluated through a Human Q Series Signal Transduction in Cancer Gene Array analysis. Nuclear NF-κB contentration and endogenous IKK activity were demonstrated by ELISA assay. The association of IKKα, IKKβ, IκBα with HSP27 and the association between IKKβ and IKKα in MHCC97H cells were determined by co-immunoprecipitation assay followed by western blot analysis.</p> <p>Results</p> <p>HSP27 protein and its phosphorylation increased in parallel with enhanced metastatic potentials of HCC cells. siRNA-mediated HSP27 knockdown in MHCC97H significantly suppressed cells migration and invasion <it>in vitro </it>and induced cell apoptosis; the prominently altered signal transduction pathway was NF-κB pathway after HSP27 knockdown in MHCC97H cells. Furthermore, inhibition of HSP27 expression led to a significant decrease of nuclear NF-κB contentration and endogenous IKK activity. In addition, HSP27 was associated with IKKα, IKKβ, IκBα in three HCC cells above. ELISA assay and western blot analysis also showed a decrease of the association between IKKβ and IKKα, the association between phosphor-HSP27 and IKK complex, and an increase of total IκBα but reducing tendency of phosphor-IκBα when HSP27 expression was efficiently knocked down in MHCC97H cells.</p> <p>Conclusion</p> <p>Altogether, these findings revealed a possible effect of HSP27 on apoptosis in metastatic HCC cells, in which HSP27 may regulate NF-kB pathway activation.</p

    Withanolides-Induced Breast Cancer Cell Death Is Correlated with Their Ability to Inhibit Heat Protein 90

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    Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity

    Contribution of Caspase(s) to the Cell Cycle Regulation at Mitotic Phase

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    Caspases have been suggested to contribute to not only apoptosis regulation but also non-apoptotic cellular phenomena. Recently, we have reported the involvement of caspase-7 to the cell cycle progression at mitotic phase by knockdown of caspase-7 using small interfering RNAs and short hairpin RNA. Here we showed that chemically synthesized broad-spectrum caspase inhibitors, which have been used to suppress apoptosis, prevented the cell proliferation in a dose-dependent manner, and that the subtype-specific peptide-based caspase inhibitor for caspase-3 and -7, but not for caspase-9, inhibited cell proliferation. It was also indicated that the BIR2 domain of X-linked inhibitor of apoptosis protein, functioning as an inhibitor for caspase-3 and -7, but not the BIR3 domain which plays as a caspase-9 inhibitor, induced cell cycle arrest. Furthermore, flow cytometry revealed that the cells treated with caspase inhibitors arrested at G2/M phase. By using HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, the prevention of the cell proliferation by caspase inhibitors induced cell cycle arrest at mitotic phase accompanying the accumulation of the substrates for APC/C, suggesting the impairment of the APC/C activity at the transition from M to G1 phases. These results indicate that caspase(s) contribute to the cell cycle regulation at mitotic phase

    Mechanisms of Hsp90 regulation

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    Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. This implicates Hsp90 in diverse biological processes that require a variety of co-ordinated regulatory mechanisms to control its activity. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters. HSF1 is itself subject to a variety of regulatory processes and can directly respond to stress. HSF1 also interacts with a variety of transcriptional factors that help integrate biological signals, which in turn regulate Hsp90 appropriately. Because of the diverse clientele of Hsp90 a whole variety of co-chaperones also regulate its activity and some are directly responsible for delivery of client protein. Consequently, co-chaperones themselves, like Hsp90, are also subject to regulatory mechanisms such as post translational modification. This review, looks at the many different levels by which Hsp90 activity is ultimately regulated

    RNF185, a Novel Mitochondrial Ubiquitin E3 Ligase, Regulates Autophagy through Interaction with BNIP1

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    Autophagy is an evolutionarily conserved catabolic process that allows recycling of cytoplasmic organelles, such as mitochondria, to offer a bioenergetically efficient pathway for cell survival. Considerable progress has been made in characterizing mitochondrial autophagy. However, the dedicated ubiquitin E3 ligases targeting mitochondria for autophagy have not been revealed. Here we show that human RNF185 is a mitochondrial ubiquitin E3 ligase that regulates selective mitochondrial autophagy in cultured cells. The two C-terminal transmembrane domains of human RNF185 mediate its localization to mitochondrial outer membrane. RNF185 stimulates LC3II accumulation and the formation of autophagolysosomes in human cell lines. We further identified the Bcl-2 family protein BNIP1 as one of the substrates for RNF185. Human BNIP1 colocalizes with RNF185 at mitochondria and is polyubiquitinated by RNF185 through K63-based ubiquitin linkage in vivo. The polyubiquitinated BNIP1 is capable of recruiting autophagy receptor p62, which simultaneously binds both ubiquitin and LC3 to link ubiquitination and autophagy. Our study might reveal a novel RNF185-mediated mechanism for modulating mitochondrial homeostasis through autophagy
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