The allegorical significance of Fortune in Dosso Dossi’s Allegory of Fortune has been largely unstudied. Though the painting’s patronage cannot be confirmed, the few scholars who have written on Dossi’s piece agree that Isabella d’Este is the most likely patron. If this is the case, then Isabella d’Este’s role as the commissioner of this work must be taken into account. This paper proposes that the Allegory of Fortune is not just an allegorical representation of the quality of Fortune, but an allegory for Isabella d’Este’s own struggles with fortune. By depicting such a temporal quality in a permanent state, Isabella d’Este was asserting her control over her own fortunes in life. This idea is echoed in other representations of Fortune, as well as in a Latin poem that claims that artists can assert their power over Fortune through the physical act of representing her. By giving shape to an intangible quality, both artists and patrons in the 16th century were able to trap Fortune and proclaim her to be their own. Yet in spite of these efforts, representations of Fortune continued to change, reaffirming her volatile nature.

Childish Gambino’s “Redbone” has incited many waves of impact across today’s pop culture media. His song uses features of the 1970s psychedelic funk movement, such as slap bass space feels and paranoia, to recall the Black Power Movement and illustrate the fear of Blackness in modern society while asking listeners to “stay woke” in political activism. This paper examines the origins of the Funkadelic movement along with its social implications within the Black Power Movement. It is then followed by a musical analysis of “Redbone” with a focus on the harmonic, melodic, and instrumental aspects of the piece and its direct relations to the 1970s movement while providing a novel variation. Cries to “stay woke” in the lyrics reemphasize the call to action, bringing wide reception and success to both the subsequent album and Glover as an artist.

In this issue of Cell Chemical Biology, Zhang et al. (2017) report a zebrafish model of Parkinson's disease (PD), incorporating the PD-protein PINK1 and rotenone, a toxin linked to PD. Using it as a drug-screening platform, they identify trifluoperazine and other piperazine phenothiazines as protective compounds that enhance autophagy independent of PINK1.

Stem cell-derived organoid technology is a powerful tool that revolutionizes the field of biomedical research and extends the scope of our understanding of human biology and diseases. Brain organoids especially open an opportunity for human brain research and modeling many human neurological diseases, which have lagged due to the inaccessibility of human brain samples and lack of similarity with other animal models. Brain organoids can be generated through various protocols and mimic whole brain or region-specific. To provide an overview of brain organoid technology, we summarize currently available protocols and list several factors to consider before choosing protocols. We also outline the limitations of current protocols and challenges that need to be solved in future investigation of brain development and pathobiology.

Introduction: Down syndrome (DS) is a genetic disorder with an extra copy of chromosome 21 and DS remains one of the most common causes of intellectual disabilities in humans. All DS patients have Alzheimers disease (AD)-like neuropathological changes including accumulation of plaques and tangles by their 40s, much earlier than the onset of such neuropathological changes in AD patients. Due to the lack of human samples and appropriate techniques, our understanding of DS neuropathology during brain development or before the clinical onset of the disease remains largely unexplored at the cellular and molecular levels. Methods: We used induced pluripotent stem cell (iPSC) and iPSC-derived 3D cortical organoids to model Alzheimers disease in Down syndrome and explore the earliest cellular and molecular changes during DS fetal brain development. Results: We report that DS iPSCs have a decreased growth rate than control iPSCs due to a decreased cell proliferation. DS iPSC-derived cortical organoids have a much higher immunoreactivity of amyloid beta (Aß) antibodies and a significantly higher amount of amyloid plaques than control organoids. Although Elisa results did not detect a difference of Aß40 and Aß42 level between the two groups, the ratio of Aß42/Aß40 in the detergent-insoluble fraction of DS organoids was significantly higher than control organoids. Furthermore, an increased Tau phosphorylation (pTau S396) in DS organoids was confirmed by immunostaining and Western blot. Elisa data demonstrated that the ratio of insoluble Tau/total Tau in DS organoids was significantly higher than control organoids. Conclusion: DS iPSC-derived cortical organoids mimic AD-like pathophysiologyical phenotype in vitro, including abnormal Aß and insoluble Tau accumulation. The molecular neuropathologic signature of AD is present in DS much earlier than predicted, even in early fetal brain development, illustrating the notion that brain organoids maybe a good model to study early neurodegenerative conditions.

Mitochondria are undoubtedly changed in Parkinsons disease (PD), and mitochondrial functions are disrupted in genetic and pharmacologic models of PD. However, many of these changes might not truly drive neurodegeneration. PD is defined by the particular susceptibility of nigrostriatal dopamine (DA) neurons, but little is understood about the mitochondria in these cells. Here, we critically review the evidence that mitochondrial stressors cause PD. We then consider how changes in the intrinsic function of mitochondria and in their mass, distribution, and dynamics might synergize with an increased need for mitochondria and produce PD, and the importance of understanding how mitochondria contribute to its pathogenesis.

In this issue of Cell Chemical Biology, Zhang et al. (2017) report a zebrafish model of Parkinson's disease (PD), incorporating the PD-protein PINK1 and rotenone, a toxin linked to PD. Using it as a drug-screening platform, they identify trifluoperazine and other piperazine phenothiazines as protective compounds that enhance autophagy independent of PINK1.