Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice

Recent human genetic studies have provided evidences that sporadic or inherited missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in alterations in FHL1 protein expression, are associated with rare congenital myopathies, including reducing body myopathy and Emery–Dreifuss muscular dystrophy. However, it remains to be clarified whether mutations in FHL1 cause skeletal muscle remodeling owing to gain- or loss of FHL1 function. In this study, we used FHL1-null mice lacking global FHL1 expression to evaluate loss-of-function effects on skeletal muscle homeostasis. Histological and functional analyses of soleus, tibialis anterior and sternohyoideus muscles demonstrated that FHL1-null mice develop an age-dependent myopathy associated with myofibrillar and intermyofibrillar (mitochondrial and sarcoplasmic reticulum) disorganization, impaired muscle oxidative capacity and increased autophagic activity. A longitudinal study established decreased survival rates in FHL1-null mice, associated with age-dependent impairment of muscle contractile function and a significantly lower exercise capacity. Analysis of primary myoblasts isolated from FHL1-null muscles demonstrated early muscle fiber differentiation and maturation defects, which could be rescued by re-expression of the FHL1A isoform, highlighting that FHL1A is necessary for proper muscle fiber differentiation and maturation in vitro. Overall, our data show that loss of FHL1 function leads to myopathy in vivo and suggest that loss of function of FHL1 may be one of the mechanisms underlying muscle dystrophy in patients with FHL1 mutations

Floating Points: From Diasporic Spaces to Multicultural Places

In the study of Asian immigrant communities and culture in North America, particularly in arts and literature, two intellectual approaches have emerged: the transnational which focuses on country and culture of origin regardless of the location of the diaspora community; and, the national which de-emphasizes diaspora in favour of a racial character distinct to the new generations of Asians born and residing in the U.S. and Canada today. In her talk, Angela Pao engages both approaches by presenting the benefits and drawbacks of examining social and cultural institutions, artistic products, and processes through a transnational and consequently de-territorialized perspective, as opposed to a domestic one that continues to emphasize Asian histories specific to a destination country or territory. Race and the context of uneven social and power relations between immigrant and local communities, more specifically, are the primary bases on which Pao examines the development of Asian immigrant culture, in particular, Chinese literature in North America, and its usefulness in helping interpret the local and global Asian immigrant experiences