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"Davis, Ryan"
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Tumour heterogeneity and metastasis at single-cell resolution
Tumours comprise a heterogeneous collection of cells with distinct genetic and phenotypic properties that can differentially promote progression, metastasis and drug resistance. Emerging single-cell technologies provide a new opportunity to profile individual cells within tumours and investigate what roles they play in these processes. This Review discusses key technological considerations for single-cell studies in cancer, new findings using single-cell technologies and critical open questions for future applications.
Lawson et al. review recent advances in single-cell technologies and discuss in detail how they can be leveraged to understand tumour heterogeneity and metastasis.
Journal Article
Gilbert Simondon's Psychic and collective individuation : a critical introduction and guide
A critical commentary on Simondon's Psychic and collective individuation. This book clarifies Simondon's complex terminology and structure through chapter by chapter commentary. It also invites a dialogue with other thinkers/philosophers and places the work in its historical context. It includes a discussion about Simondon's relevance to current ideas about biopolitics and post-Nietzschean ethics.
Book
Gaslighting Citizens
Gaslighting brings its victims to doubt the sources of their evidence. This article holds that political gaslighting, by leading citizens to hold beliefs disconnected from the available evidence, poses a distinctive threat to democratic politics. But holding “audacious beliefs”—beliefs that are ahead of the evidence—can serve as a core ingredient for democratic movements. This creates a dilemma for citizens, who must choose between two kinds of evidential policies. How can they protect themselves from gaslighting without rendering themselves insusceptible to the mobilizing efforts central to democratic politics? Citizens, then, face a standing challenge: to remain open to the bully pulpit while vigilant against the gaslighter’s epistemic bullying.
Journal Article
Jack Kirby : 100th celebration collection
\"Long live the king! He was one of the most gifted artists and influential storytellers of the 20th century. He pioneered entire genres and co-created whole universes with the stroke of a pencil. He is Jack Kirby, the King of Comics. Now DC celebrates his 100th birthday with this all-star collection of all-new stories featuring some of this visionary master's greatest creations! Enter the dangerous dreamworld of Sandman, the Master of Nightmares! Battle for control the mean streets of World War II-era New York City with the Newsboy Legion and the Boy Commandos! Escape certain death with Shilo \"Mister Miracle\" Norman as he runs from the clutches of the Black Racer! Fight the crime wave of the century with the masked vigilante called Manhunter! Burn in the fiery nether world of Etrigan the Demon! And tremble before the awesome evil of the Lord of Apokolips hmself ... Darkseid!\" -- Page 4 of cover.
Book
Mitochondrial Dysfunction in Parkinson’s Disease: New Mechanistic Insights and Therapeutic Perspectives
Purpose of ReviewParkinson’s disease (PD) is a complex neurodegenerative disorder, the aetiology of which is still largely unknown. Overwhelming evidence indicates that mitochondrial dysfunction is a central factor in PD pathophysiology. Here we review recent developments around mitochondrial dysfunction in familial and sporadic PD, with a brief overview of emerging therapies targeting mitochondrial dysfunction.Recent FindingsIncreasing evidence supports the critical role for mitochondrial dysfunction in the development of sporadic PD, while the involvement of familial PD-related genes in the regulation of mitochondrial biology has been expanded by the discovery of new mitochondria-associated disease loci and the identification of their novel functions.SummaryRecent research has expanded knowledge on the mechanistic details underlying mitochondrial dysfunction in PD, with the discovery of new therapeutic targets providing invaluable insights into the essential role of mitochondria in PD pathogenesis and unique opportunities for drug development.
Journal Article
Virally encoded interleukin-6 facilitates KSHV replication in monocytes and induction of dysfunctional macrophages
Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus and the etiologic agent of Kaposi’s sarcoma and hyperinflammatory lymphoproliferative disorders. Understanding the mechanism by which KSHV increases the infected cell population is crucial for curing KSHV-associated diseases. Using scRNA-seq, we demonstrate that KSHV preferentially infects CD14 + monocytes, sustains viral lytic replication through the viral interleukin-6 (vIL-6), which activates STAT1 and 3, and induces an inflammatory gene expression program. To study the role of vIL-6 in monocytes upon KSHV infection, we generated recombinant KSHV with premature stop codon (vIL-6(-)) and its revertant viruses (vIL-6(+)). Infection of the recombinant viruses shows that both vIL-6(+) and vIL-6(-) KSHV infection induced indistinguishable host anti-viral response with STAT1 and 3 activations in monocytes; however, vIL-6(+), but not vIL-6(-), KSHV infection promoted the proliferation and differentiation of KSHV-infected monocytes into macrophages. The macrophages derived from vIL-6(+) KSHV infection showed a distinct transcriptional profile of elevated IFN-pathway activation with immune suppression and were compromised in T-cell stimulation function compared to those from vIL-6(-) KSHV infection or uninfected control. Notably, a viral nuclear long noncoding RNA (PAN RNA), which is required for sustaining KSHV gene expression, was substantially reduced in infected primary monocytes upon vIL-6(-) KSHV infection. These results highlight the critical role of vIL-6 in sustaining KSHV transcription in primary monocytes. Our findings also imply a clever strategy in which KSHV utilizes vIL-6 to secure its viral pool by expanding infected monocytes via differentiating into longer-lived dysfunctional macrophages. This mechanism may facilitate KSHV to escape from host immune surveillance and to support a lifelong infection.
Journal Article
The Flash
\"When Wally West, the adolescent nephew of the Flash's fiancee accidentally gained powers of superspeed, he became the Scarlet Speedster's sidekick. Growing up as his hero's protege, Kid Flash had a childhood of amazing action and adventure. But on the day that The Flash died, Wally's carefree adolescence abruptly ended and his life as an adult began. THE FLASH BY MARK WAID BOOK ONE looks back at Wally's earliest days as the Kid Flash and explores the gamut of his emotions and experiences from his first day as a child hero to his succession of Barry Allen as the new Flash. A journey full of humor and drama, this story shows just how much Wally West loves being the fastest man alive\"-- Provided by publisher.
Book
Evidence for a semisolid phase state of aerosols and droplets relevant to the airborne and surface survival of pathogens
The phase state of respiratory aerosols and droplets has been linked to the humidity-dependent survival of pathogens such as SARS-CoV-2. To inform strategies to mitigate the spread of infectious disease, it is thus necessary to understand the humidity-dependent phase changes associated with the particles in which pathogens are suspended. Here, we study phase changes of levitated aerosols and droplets composed of model respiratory compounds (salt and protein) and growth media (organic–inorganic mixtures commonly used in studies of pathogen survival) with decreasing relative humidity (RH). Efflorescence was suppressed in many particle compositions and thus unlikely to fully account for the humidity-dependent survival of viruses. Rather, we identify organic-based, semisolid phase states that form under equilibrium conditions at intermediate RH (45 to 80%). A higher-protein content causes particles to exist in a semisolid state under a wider range of RH conditions. Diffusion and, thus, disinfection kinetics are expected to be inhibited in these semisolid states. These observations suggest that organic-based, semisolid states are an important consideration to account for the recovery of virus viability at low RH observed in previous studies. We propose a mechanism in which the semisolid phase shields pathogens from inactivation by hindering the diffusion of solutes. This suggests that the exogenous lifetime of pathogens will depend, in part, on the organic composition of the carrier respiratory particle and thus its origin in the respiratory tract. Furthermore, this work highlights the importance of accounting for spatial heterogeneities and time-dependent changes in the properties of aerosols and droplets undergoing evaporation in studies of pathogen viability.
Journal Article