Uncoordinated Transcription and Compromised Muscle Function in the Lmna-Null Mouse Model of Emery-Dreifuss Muscular Dystrophy

LMNA encodes both lamin A and C: major components of the nuclear lamina. Mutations in LMNA underlie a range of tissue-specific degenerative diseases, including those that affect skeletal muscle, such as autosomal-Emery-Dreifuss muscular dystrophy (A-EDMD) and limb girdle muscular dystrophy 1B. Here, we examine the morphology and transcriptional activity of myonuclei, the structure of the myotendinous junction and the muscle contraction dynamics in the lmna-null mouse model of A-EDMD. We found that there were fewer myonuclei in lmna-null mice, of which ∼50% had morphological abnormalities. Assaying transcriptional activity by examining acetylated histone H3 and PABPN1 levels indicated that there was a lack of coordinated transcription between myonuclei lacking lamin A/C. Myonuclei with abnormal morphology and transcriptional activity were distributed along the length of the myofibre, but accumulated at the myotendinous junction. Indeed, in addition to the presence of abnormal myonuclei, the structure of the myotendinous junction was perturbed, with disorganised sarcomeres and reduced interdigitation with the tendon, together with lipid and collagen deposition. Functionally, muscle contraction became severely affected within weeks of birth, with specific force generation dropping as low as ∼65% and ∼27% of control values in the extensor digitorum longus and soleus muscles respectively. These observations illustrate the importance of lamin A/C for correct myonuclear function, which likely acts synergistically with myotendinous junction disorganisation in the development of A-EDMD, and the consequential reduction in force generation and muscle wasting

Violence

Written in the shadow of the approaching millennium, American literature in the 1990s was beset by bleak announcements of the end of books, the end of postmodernism, and even the end of literature. Yet, as conservative critics marked the century's twilight hours by launching elegies for the conventional canon, American writers proved the continuing vitality of their literature by reinvigorating inherited forms, by adopting and adapting emerging technologies to narrative ends, and by finding new voices that had remained outside that canon for too long. By reading 1990s literature in a sequence of shifting contexts - from independent presses to the AIDS crisis; from angelology to virtual reality - American Literature in Transition, 1990–2000 provides the fullest map yet of the changing shape of a rich and diverse decade's literary production. It offers new perspectives on the period's well-known landmarks, Toni Morrison, Thomas Pynchon, David Foster Wallace, but also overdue recognition to writers such as Ana Castillo, Evan Dara, Steve Erickson, and Carole Maso

A Grenade With the Fuse Lit: William S. Burroughs and Retroactive Utopias in Cities of the Red Night

In 1981, William S. Burroughs—often considered a writer of devastatingly apocalyptic dystopian vision—published "Cities of the Red Night," his first foray into utopian writing. This article examines Burroughs's conception of the "retroactive utopia." It highlights Burroughs's ambivalence toward utopian projects and invokes both his hope and his disappointment in the ability for utopian writing to engender political change

The Indignant Multitude: Spinozist Marxism after Empire

The Spinoza invoked by Michael Hardt and Antonio Negri in their work together seems quite distinct from the one encountered in Spinoza’s thought. Sean Grattan asks if a truncated Spinoza can be useful for a liberatory politic

Monstrous Utopia in Toni Morrison’s Paradise

Contemporary US literature appears to have shied away from considerations of utopia. “Monstrous Utopia in Toni Morrison's Paradise” argues that Morrison creates two utopian communities to explore the ambiguous relationship between utopia and political imagination. The importance of communication in the small, unplanned utopian community of the Convent starkly exposes the danger of closing narrative possibilities as represented by the planned utopian community of Ruby. Utopian narratives, more than any other genre, create an argument for alternatives to the status quo. By examining intersections between utopian theory, Michael Hardt and Antonio Negri's concept of the multitude, and Morrison's Paradise, a space opens up for reconsidering ambiguous narratives of utopia in contemporary US fictio