Dysregulation of eating behavior can lead to obesity, which affects 10% of the adult population worldwide and accounts for nearly 3 million deaths every year. Despite this burden on society, we currently lack effective pharmacological treatment options to regulate appetite. We used Drosophila melanogaster larvae to develop a high-throughput whole organism screen for drugs that modulate food intake. In a screen of 3630 small molecules, we identified the serotonin (5-hydroxytryptamine or 5-HT) receptor antagonist metitepine as a potent anorectic drug. Using cell-based assays we show that metitepine is an antagonist of all five Drosophila 5-HT receptors. We screened fly mutants for each of these receptors and found that serotonin receptor 5-HT2A is the sole molecular target for feeding inhibition by metitepine. These results highlight the conservation of molecular mechanisms controlling appetite and provide a method for unbiased whole-organism drug screens to identify novel drugs and molecular pathways modulating food intake.

Neurons are chiefly non-renewable; thus, cytolytic immune strategies to clear or control neurotropic viral infections could have lasting neurological consequences. Interferon-gamma (IFNγ) is a potent anti-viral cytokine that is critical for non-cytolytic clearance of multiple neurotropic viral infections, including measles virus (MV); however, the downstream pathways through which IFNγ functions in neurons have not been defined. Unlike most cell types studied to date in which IFNγ affects gene expression via rapid and robust activation of STAT1, basal STAT1 levels in primary hippocampal neurons are constitutively low, resulting in attenuated STAT1 activation and consequently slower kinetics of IFNγ-driven STAT1-dependent gene expression. Given this altered expression and activation of STAT1 in neurons, we sought to determine whether STAT1 was required for IFNγ-mediated protection from infection in neurons. To do so, we evaluated the consequences of MV challenge of STAT1-deficient mice and primary hippocampal neurons explanted from these mice. Surprisingly, the absence of STAT1 did not restrict the ability of IFNγ to control viral infection either in vivo or ex vivo. Moreover, the canonical IFNγ-triggered STAT1 gene expression profile was not induced in STAT1-deficient neurons, suggesting that IFNγ regulates neuronal STAT1-independent pathways to control viral replication.

We report a family with markedly variable myopathic weakness due to facioscapulohumeral muscular dystrophy (FSHD). The proband developed mild late-onset proximal limb weakness. Her two daughters had severe infantile facial diplegia, initially diagnosed as Möbius syndrome, and mild childhood-onset limb weakness and scapular winging. Results of facial muscle electromyography and muscle histopathology supported a myopathic disorder. This case study further highlights the broad clinical spectrum and intrafamily variability in FSHD, and the occasional absence of a positive correlation between fragment size and disease onset. Moreover, this study underscores the importance of considering FSHD in cases of infantile facial diplegia, especially in patients not demonstrating the full clinical features of Möbius syndrome. In difficult cases, facial muscle electromyography may help to differentiate myopathic from neuropathic weakness, and help guide further diagnostic studies.

While the substantial literature on lay health beliefs gives some consideration to older people's conceptions of health and illness, it is material which has yet to be examined from the perspective of postmodern theory. This article, therefore, critically examines the value of using ideas from postmodernism in such a context and focuses on data obtained from a series of in-depth interviews with a sample of fifteen older people. During the interviews they were asked to talk about themselves in relation to issues which included health, illness, disease, death and dying. What they said revealed that, while medicine remained a location of power and knowledge, many of their health beliefs were nonetheless at odds with conventional medicine and indeed with the traditionally passive role of the NHS patient. In conclusion, we suggest that, whilst not always in an explicit or conscious sense, interviewees were discovering self-empowering strategies by questioning the meta-narratives through which the social world is fabricated.