The Challenges of Multiplicity

A Review of Inessential Woman: Problems of Exclusion in Feminist Thought by Elizabeth V. Spelma

Native Functions of the Androgen Receptor are Essential to Pathogenesis in a Drosophila Model of Spinobulbar Muscular Atrophy

Spinobulbar muscular atrophy (SBMA) is a progressive, late-onset disease characterized by degeneration of motor neurons in the brainstem and spinal cord. The disease is caused by expansion of a polyglutamine tract in the androgen receptor (AR) and is dependent on exposure to AR ligand. The expanded polyglutamine tract confers toxic function to the protein through unknown mechanisms, although the ligand-dependent nature of SBMA suggests that the mechanism of pathogenesis may be tied to ligand-dependent alterations in AR function. However, whether toxicity is mediated by native AR function or a novel AR function is unknown. We systematically investigated ligand-dependent modifications of AR in a Drosophila model of SBMA. We demonstrate in vivo that nuclear translocation of mutant AR is necessary but not sufficient for toxicity and that DNA binding by AR is necessary for toxicity. Mutagenesis studies demonstrated that a functional AF-2 domain is essential for toxicity, a finding corroborated by a genetic screen that identified AF-2 interactors as dominant modifiers of degeneration. As proof of this principle, we perform epistasis experiments using the AR coregulator limpet, which we find modifies polyglutamine-expanded AR toxicity in an AF-2-dependent manner. In addition, we use expression profiling to examine the molecular phenotype of polyglutamine-expanded AR degeneration, revealing that expression of wild-type AR results in a molecular phenotype that is very similar to that caused by polyglutamine-expanded AR. These findings suggest that expanded-polyglutamine AR toxicity may be mediated by amplification of normal function, a mechanism that may be broadly applicable to other polyglutamine diseases

Understanding gendered influences on women's reproductive health in Pakistan: Moving beyond the autonomy paradigm

Recent research and policy discourse commonly view the limited autonomy of women in developing countries as a key barrier to improvements in their reproductive health. Rarely, however, is the notion of women's autonomy interrogated for its conceptual adequacy or usefulness for understanding the determinants of women's reproductive health, effective policy formulation or program design. Using ethnographic data from 2001, including social mapping exercises, observation of daily life, interviews, case studies and focus group discussions, this paper draws attention to the incongruities between the concept of women's autonomy and the gendered social, cultural, economic and political realities of women's lives in rural Punjab, Pakistan. These inadequacies include: the concept's undue emphasis on women's independent, autonomous action; a lack of attention to men and masculinities; a disregard for the multi-sited constitution of gender relations and gender inequality; an erroneous assumption that uptake of reproductive health services is an indicator of autonomy; and a failure to explore the interplay of other axes of disadvantage such as caste, class or socio-economic position. This paper calls for alternative, more nuanced, theoretical approaches for conceptualizing gender inequalities in order to enhance our understanding of women's reproductive wellbeing in Pakistan. The extent to which our arguments may be relevant to the wider South Asian context, and women's lives in other parts of the world, is also discussed

Why is autophagy important in human diseases?

The process of macroautophagy (referred to hereafter as autophagy), is generally characterized by the prominent formation of autophagic vesicles in the cytoplasm. In the past decades, studies of autophagy have been vastly expanded. As an essential process to maintain cellular homeostasis and functions, autophagy is responsible for the lysosome-mediated degradation of damaged proteins and organelles, and thus misregulation of autophagy can result in a variety of pathological conditions in human beings. Although our understanding of regulatory pathways that control autophagy is still limited, an increasing number of studies have shed light on the importance of autophagy in a wide range of physiological processes and human diseases. The goal of the reviews in the current issue is to provide a general overview of current knowledge on autophagy. The machinery and regulation of autophagy were outlined with special attention to its role in diabetes, neurodegenerative disorders, infectious diseases and cancer

The Convention for the Rights of Persons with Disabilities and Article 12: prospective feminist lessons against the “Will and Preferences” paradigm

Human rights have recently impacted on current conceptualisations of the rights and obligations owed to individuals with impairments, culminating in the UN Convention for the Rights of Persons with Disabilities. Particularly significant is Article 12, where interpretations have heralded a “will and preferences” paradigm which rejects substituted decision-making mechanisms, even in situations where an individual should make personally harmful or unwise decisions about their treatment, care, or relationships. This paper explores problems with “strict” and “flexible” interpretations of Article 12, focusing specifically on safeguarding issues in cases of relational abuse, exploitation, and coercion. Drawing analogies with feminist arguments opposing violence against women in the domestic sphere, I challenge the private/public and individualistic account of autonomy which is implicit in interpretations of the “will and preferences” paradigm, and suggest that proponents of Article 12 should consider the possible justifiability of expanded protectionist measures in cases of abuse involving individuals with impairments

Can medical students accurately predict their learning? A study comparing perceived and actual performance in neuroanatomy

It is important that clinicians are able to adequately assess their level of knowledge and competence in order to be safe practitioners of medicine. The medical literature contains numerous examples of poor self-assessment accuracy amongst medical students over a range of subjects however this ability in neuroanatomy has yet to be observed. Second year medical students attending neuroanatomy revision sessions at the University of Southampton and the competitors of the National Undergraduate Neuroanatomy Competition were asked to rate their level of knowledge in neuroanatomy. The responses from the former group were compared to performance on a ten item multiple choice question examination and the latter group were compared to their performance within the competition. In both cohorts, self-assessments of perceived level of knowledge correlated weakly to their performance in their respective objective knowledge assessments (r = 0.30 and r = 0.44). Within the NUNC, this correlation improved when students were instead asked to rate their performance on a specific examination within the competition (spotter, rS = 0.68; MCQ, rS = 0.58). Despite its inherent difficulty, medical student self-assessment accuracy in neuroanatomy is comparable to other subjects within the medical curriculum. Anat Sci Educ. (c) 2016 American Association of Anatomists

The South African redistribution imperative: Incongruities in theory and practice

It has partly been assumed that the constitutional obligation to pay compensation for expropriations is to blame for the slow pace at which land has been redistributed in South Africa. However, this assumption requires careful analysis and reflection, with reference to the imperfections of the policies and laws that set out to address landlessness, as well as the underlying theoretical approach to economic justice. This article questions the purpose for which land reform beneficiaries acquire land, with reference to the role that property should ideally fulfil for the landless. The article makes a number of observations to cast light on why the redistribution of land has been alarmingly slow, where inconsistencies and loopholes exist in the programme, and whether expropriations for nil compensation will make any difference in remedying existing failures in the redistribution programme