26 research outputs found

    New genetic loci link adipose and insulin biology to body fat distribution.

    Get PDF
    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    A Discussion of the Feasibility of Bakhtin’s Polyphony—Katherine Anne Porter’s Ship of Fools as an Example

    No full text
    [[abstract]]俄國文學評論家米哈伊爾‧巴赫金所提出的觀念與諸多後現代文學批評觀點有濃厚的相關性,尤其是「作者之死」,促成了當代「讀者反應理論」以及相關支派的活絡與興盛。巴赫金提出「多音」的觀點,主張在小說寫作過程當中,作者的首要任務就是要完整地呈現角色的話語。作者應該盡力釋放他對角色的影響力,以便能夠完整地呈現角色的道德觀與意識型態。巴赫金的理論固然影響深遠,卻也備受質疑。許多知名的小說家與文學評論家如美國的那博可夫、亨利‧詹母斯、英國的E.M.福斯特、法國新小說學派發起人葛力葉等,都認為作者對於其所寫作小說的重要性不可被磨滅或削減。以那博可夫為例,他認為小說家結合「說故事人」、「教育者」與「魔術師」三種特色,而其中「魔術師」一項最能決定這一位小說家的成功與否。顯然地,巴赫金意圖削減作者影響力的主張與前述等文學評論家相佐。為了指出巴赫金主張的盲點,本論文分析當代美國小說《愚人船》中作者話語、英雄話語,與兩種話語之間的對話。以巴赫金的理論作為分析藍本可發現,《愚人船》相當符合「多音」的要件,作者波特的話語幾乎未曾介入或限制角色的話語,並且,波特也未如其他小說家,區分主要角色與次要角色的話語,而是一視同仁地呈現所有角色的話語,使不同的社會話語齊鳴,十足顯現「眾聲喧嘩」的精神。然而,《愚人船》的小說語言雖然最符合巴赫金對小說的主張,卻被大部分的評論家批評缺乏文學寫作技巧,沒有明確的主題,更遑論精雕細琢的藝術手法,整本小說只是概略地呈現一群油輪旅客的話語,來做為真實生活與社會語言的寫照。簡而言之,那博可夫所謂的小說家的「魔術師」特質,葛力葉的「作家事業唯一的表現方式」,在可被稱為「眾聲喧嘩」典範的《愚人船》當中,了無蹤跡。文學作品乃是作家「意圖」宰制之下的美學產物,每一部文學作品,依據作家的寫作動機與目的,都必須有所聚焦,有所強化某個主題或某種道德觀。在小說的架構之下,作者話語無可避免地背負重責大任,除了必須選擇性地呈現角色話語之外,作者話語更在小說中,以各式各樣的設計做為小說本身的敘述架構,以致於能明確闡述小說家所欲傳達的訊息。針對巴赫金的「眾聲喧嘩」,我們應由小說創作的實際過程,來重新思考該觀點的適切性。[[abstract]]Mikhail Bakhtin is generally recognized as a pioneer critic of the privileged position of the author in his discussions of Western novel. He extensively pushed forward the concept that the novelist must abandon his domination over the character’s discourse in order to enable the full blossoming of the character’s ideology and consciousness. However, several novelists and literary critics, for example, Henry James, Vladimir Nabokov, David Lodge, Alain Robbe-Grillet, and E.M. Forster made similar statements in which they believed that the discourse of the author could not be annihilated since it struck its roots in every aspect of the novel, which surely brought a profound influence on the style of the novel. To pinpoint the weaknesses of Bakhtin’s polyphony, this paper intends to examine the novelistic language of American writer Katherine Anne Porter’s Ship of Fools. The language of the novel is almost an ideal to that of Bakhtin’s most desired mode of writing. Nevertheless, the novel has failed to be ranked by numerous critics as a classic mostly because literary techniques, or what Nabokov acclaimed the “magical power” and “talent” of the novelist, are nowhere in sight in this novel. Therefore, a painstaking record of social languages like Ship of Fools, though celebrating the truth of confrontations by way of presenting multifarious human consciousnesses, fails to become an acclaimed literary work as it leaves out the literary techniques that are inevitably required in a serious work of art

    Functional Genomics Reveals Linkers Critical for Influenza Virus Polymerase

    No full text
    Influenza virus mRNA synthesis by the RNA-dependent RNA polymerase involves binding and cleavage of capped cellular mRNA by the PB2 and PA subunits, respectively, and extension of viral mRNA by PB1. However, the mechanism for such a dynamic process is unclear. Using high-throughput mutagenesis and sequencing analysis, we have not only generated a comprehensive functional map for the microdomains of individual subunits but also have revealed the PA linker to be critical for polymerase activity. This PA linker binds to PB1 and also forms ionic interactions with the PA C-terminal channel. Nearly all mutants with five-amino-acid insertions in the linker were nonviable. Our model further suggests that the PA linker plays an important role in the conformational changes that occur between stages that favor capped mRNA binding and cleavage and those associated with viral mRNA synthesis. IMPORTANCE The RNA-dependent RNA polymerase of influenza virus consists of the PB1, PB2, and PA subunits. By combining genome-wide mutagenesis analysis with the recently discovered crystal structure of the influenza polymerase heterotrimer, we generated a comprehensive functional map of the entire influenza polymerase complex. We identified the microdomains of individual subunits, including the catalytic domains, the interaction interfaces between subunits, and nine linkers interconnecting different domains. Interestingly, we found that mutants with five-amino-acid insertions in individual linkers were nonviable, suggesting the critical roles these linkers play in coordinating spatial relationships between the subunits. We further identified an extended PA linker that binds to PB1 and also forms ionic interactions with the PA C-terminal channel
    corecore