Un-done: The historiographical dialogue between past and present

Art critic for The Nation and professor of at Columbia, Arthur C. Danto led the charge with his essay “The End of Art” in 1984 to declare the end of art. Thirty-eight years later, the awareness of colonial problematics in the elite institutionalism of art history today warrants a reanalysis of art historical ontologies of progress (and their ties to colonialism), which have seemingly disbanded in the discipline’s current rhetoric. Because Danto’s historical framework to end art focuses on progress through artistic means, does it fall short or even negate itself by missing the deconstruction of colonial afterlives still present in art institutionalism? Moreover, does Danto’s end to art ultimately reiterate colonial and imperial dictations over time, and thus undercut a historical futurity for “non-Western” “artists”? In comparing Danto’s theoretical discipline with the work of Titus Kapar, Yuki Kihara, and Jason Garcia (Okuu Pin), I present a hypothetical dialogue between the art historical constructs of time and the present investment in decolonizing art with a critique through appropriation. Kaphar’s work underlines how representation can challenge the game of identity performance for the benefit of institutions, Kihara challenges the pervasive ignorance towards stereotyping Pacific Islanders by resisting and confusing the West-East binary boundaries, while Garcia challenges the hero complex historical figures still have in popular culture even if they are academically deconstructed. Ultimately, they perform a legitimacy to an end of Western hegemony that Danto alludes to

Reconstruction of destruction – in vitro reconstitution methods in autophagy research

International audienceAutophagy is one of the most elaborative membrane remodeling systems in eukaryotic cells. Its major function is to recycle cytoplasmic material by delivering it to lysosomes for degradation. To achieve this, a membrane cisterna is formed that gradually captures cargo such as organelles or protein aggregates. The diversity of cargo requires autophagy to be highly versatile to adapt the shape of the phagophore to its substrate. Upon closure of the phagophore, a double-membrane-surrounded autophagosome is formed that eventually fuses with lysosomes. In response to environmental cues such as cytotoxicity or starvation, bulk cytoplasm can be captured and delivered to lysosomes. Autophagy thus supports cellular survival under adverse conditions. During the past decades, groundbreaking genetic and cell biological studies have identified the core machinery involved in the process. In this Review, we are focusing on in vitro reconstitution approaches to decipher the details and spatiotemporal control of autophagy, and how such studies contributed to our current understanding of the pathways in yeast and mammals. We highlight studies that revealed the function of the autophagy machinery at a molecular level with respect to its capacity to remodel membranes

Potential novel pharmacological therapies for myocardial remodelling

Left ventricular (LV) remodelling remains an important treatment target in patients after myocardial infarction (MI) and chronic heart failure (CHF). Accumulating evidence has supported the concept that beneficial effects of current pharmacological treatment strategies to improve the prognosis in these patients, such as angiotensin-converting enzyme (ACE) inhibition, angiotensin type 1 receptor blocker therapy, and beta-blocker therapy, are related, at least in part, to their effects on LV remodelling and dysfunction. However, despite modern reperfusion therapy after MI and optimized treatment of patients with CHF, LV remodelling is observed in a substantial proportion of patients and is associated with an adverse clinical outcome. These observations call for novel therapeutic strategies to prevent or even reverse cardiac remodelling. Recent insights from experimental studies have provided new targets for interventions to prevent or reverse LV remodelling, i.e. reduced endothelial nitric oxide (NO) synthase-derived NO availability, activation of cardiac and leukocyte-dependent oxidant stress pathways, inflammatory pathway activation, matrix-metalloproteinase activation, or stem cell transfer and delivery of novel paracrine factors. An important challenge in translating these observations from preclinical studies into clinical treatment strategies relates to the fact that clinical studies are designed on top of established pharmacological therapy, whereas most experimental studies have tested novel interventions without concomitant drug regimens such as ACE inhibitors or beta-blockers. Therefore, animal studies may overestimate the effect of potential novel treatment strategies on LV remodelling and dysfunction, since established pharmacological therapies may act, in part, via identical or similar signalling pathways. Nevertheless, preclinical studies provide essential information for identifying potential novel targets, and their potential drawbacks, and are required for developing novel clinical treatment strategies to prevent or reverse LV remodelling and dysfunctio

Extending the host range of Listeria monocytogenes by rational protein design

SummaryIn causing disease, pathogens outmaneuver host defenses through a dedicated arsenal of virulence determinants that specifically bind or modify individual host molecules. This dedication limits the intruder to a defined range of hosts. Newly emerging diseases mostly involve existing pathogens whose arsenal has been altered to allow them to infect previously inaccessible hosts. We have emulated this chance occurrence by extending the host range accessible to the human pathogen Listeria monocytogenes by the intestinal route to include the mouse. Analyzing the recognition complex of the listerial invasion protein InlA and its human receptor E-cadherin, we postulated and verified amino acid substitutions in InlA to increase its affinity for E-cadherin. Two single substitutions increase binding affinity by four orders of magnitude and extend binding specificity to include formerly incompatible murine E-cadherin. By rationally adapting a single protein, we thus create a versatile murine model of human listeriosis

The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy

Autophagosomes are double-membrane vesicles that sequester cytoplasmic material for lysosomal degradation. Their biogenesis is initiated by recruitment of Atg9-vesicles to the phagophore assembly site. This process depends on the regulated activation of the Atg1-kinase complex. However, the underlying molecular mechanism remains unclear. Here we reconstitute this early step in autophagy from purified components in vitro. We find that on assembly from its cytoplasmic subcomplexes, the Atg1-kinase complex becomes activated, enabling it to recruit and tether Atg9-vesicles. The scaffolding protein Atg17 targets the Atg1-kinase complex to autophagic membranes by specifically recognizing the membrane protein Atg9. This interaction is inhibited by the two regulatory subunits Atg31 and Atg29. Engagement of the Atg1-Atg13 subcomplex restores the Atg9-binding and membrane-tethering activity of Atg17. Our data help to unravel the mechanism that controls Atg17-mediated tethering of Atg9-vesicles, providing the molecular basis to understand initiation of autophagosome-biogenesis

TECPR1 promotes aggrephagy by direct recruitment of LC3C autophagosomes to lysosomes

The accumulation of protein aggregates is involved in the onset of many neurodegenerative diseases. Aggrephagy is a selective type of autophagy that counteracts neurodegeneration by degrading such aggregates. In this study, we found that LC3C cooperates with lysosomal TECPR1 to promote the degradation of disease-related protein aggregates in neural stem cells. The N-terminal WD-repeat domain of TECPR1 selectively binds LC3C which decorates matured autophagosomes. The interaction of LC3C and TECPR1 promotes the recruitment of autophagosomes to lysosomes for degradation. Augmented expression of TECPR1 in neural stem cells reduces the number of protein aggregates by promoting their autophagic clearance, whereas knockdown of LC3C inhibits aggrephagy. The PH domain of TECPR1 selectively interacts with PtdIns(4)P to target TECPR1 to PtdIns(4)P containing lysosomes. Exchanging the PH against a tandem-FYVE domain targets TECPR1 ectopically to endosomes. This leads to an accumulation of LC3C autophagosomes at endosomes and prevents their delivery to lysosomes. Many neurodegenerative disorders are characterised by the accumulation of protein aggregates in neurons. Here, the authors show that the lysosomal protein TECPR1 selectively recruits mature autophagosomes via an interaction with LC3C to break down protein aggregates in neural stem cells

An Assessment of the “Sweating Sickness” Affecting England During the Tudor Dynasty

While historiography and interest in Tudor England at both the popular and specialist levels presents few signs of diminishing, there may nonetheless exist a sense that we have little left to learn about this period and its culture. A notable gap in our knowledge, however, remains regarding the mysterious disease known only as “sweating sickness” or sudor anglicus. This dissertation addresses and evaluates this disease from the perspective of the history of science, and in doing so, it makes three key arguments. First, this project examines how the early modern science and medicine known and practiced by Tudor subjects influenced their perceptions of this new disease, leaving them in a mostly helpless position from which to combat it and indeed often wondering if the unknown illness might represent a divine judgment, especially in the form of questioning a dubious claim to monarchy made by the first Tudor ruler, Henry VII. Second, the dissertation offers a detailed and layered thesis concluding that the disease was ultimately caused by an earlier version of the louping-ill virus, or LIV, a virus and accompanying illness which continued to affect parts of Western Europe, with its own unique strain still extant within Britain. The third argument will return to the opening statement of this abstract, and reveal how this more thorough and unique treatment of Tudor historiography does much to further our understanding of the Tudors and their citizens, all the more relevant since the “Sweat” even now is typically either mentioned in passing, or not at all, but those who write about this period of history