Integrated Calendar

Precise protein folding by the endoplasmic reticulum (ER) supports homeostasis, while cumulative protein misfolding causes ER stress and promotes disease. The kinases PERK and IRE1 help orchestrate the unfolded protein response (UPR) to alleviate ER stress; however, if stress persists, the UPR activates apoptosis to eliminate the damaged cell. We have previously shown that PERK drives cell death via transcriptional up-regulation of the pro-apoptotic death receptor DR5; we further showed that IRE1—which harbors both kinase and RNase modules—blocks apoptosis through regulated IRE1-dependent mRNA decay (RIDD) of DR5 (Lu et al, Science 2014). Recently, we turned to investigate the paradoxical observation that under irresolvable ER stress PERK activity persists, while IRE1 function attenuates. We discovered that PERK governs the attenuation of IRE1, through a phosphatase called RNA polymerase II-associated protein 2 (RPAP2). RPAP2 reverses IRE1 phosphorylation, inhibiting IRE1 RNase activation. This disrupts IRE1-dependent generation of the cytoprotective transcription factor XBP1s and dampens ER-associated degradation of misfolded proteins. Furthermore, it inhibits RIDD, thereby licensing DR5-mediated caspase activation and apoptotic cell death. Thus, under excessive ER stress, PERK attenuates IRE1 via RPAP2 to abort failed adaptation and trigger an apoptotic cell fate.

Joseph Süss Oppenheimer—"Jew Süss"—is one of the most iconic figures in the history of an-ti-Semitism. Originally from Heidelberg, in 1733 Oppenheimer became the "court Jew" of the duke of the small German state of Württemberg. When the duke died unexpectedly a few years later, the Württemberg authorities arrested Oppenheimer, put him on trial, and con-demned him to death for unspecified "misdeeds." On February 4, 1738, Oppenheimer was hanged in front of a large crowd just outside Stuttgart. It was one of the most sensational exe-cutions of the entire eighteenth century.

This lecture by Prof. Yair Mintzker (Princeton University) is based on his new book, “The Many Deaths of Jew Süss: The Notorious Trial and Execution of an Eighteen Century Court Jew” (Princeton UP, 2017). It will concentrate on the tension between the historical figure of “Jew Süss” as reflected in eighteenth-century sources on the one hand, and, on the other hand, the widespread and often cynical use of this figure in later works of fiction, chief among them the vicious Nazi propaganda movie "Jew Süss,” which was made in 1940 at the behest of Joseph Goebbels.

The atmospheric circulation determines the structure of Earth’s climate. Changes in the circulation, such as meridional shifts in the circulation patterns can lead to dramatic changes in the local climate. Increased greenhouse gas emission is expected to change the vertical and meridional temperature profile and affect the atmospheric circulation. Climate models predict that greenhouse gas-induced climate change would cause a warming of the troposphere and cooling of the stratosphere, as well as a poleward and upward shift of the midlatitude jet stream and storm tracks - the major components of the extratropical circulation. The response of the atmospheric circulation to climate change is difficult to explain, due to nonlinear dynamical feedbacks within the system. Previous studies have attempted to explain the poleward shift of the jet stream in response to climate change based on different dynamical mechanisms. Here we propose an alternative approach of connecting the energy and momentum flux in order to explain the jet shift based on energy balance considerations.

Cell-free circulating DNA (cfDNA), released from dying cells, is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. We developed a method of detecting tissue-specific cell death in humans, based on tissue-specific methylation patterns of DNA circulating in plasma. We interrogated tissue-specific methylome datasets to identify cell type-specific DNA methylation signatures, and established a method to detect these in mixed DNA samples and in cfDNA isolated from plasma. Using this new type of biomarker it is possible to detect the presence of cfDNA fragments derived from multiple tissues in healthy individuals and in pathologies including cancer, myocardial infarction, sepsis, neurodegeneration and more. In the long run we envision this approach opening a minimally-invasive window for monitoring and diagnosis of a broad spectrum of human pathologies, as well as better understanding of normal tissue dynamics.

Understanding how social influence shapes biological processes is a central challenge in contemporary science, essential for achieving progress in a variety of fields ranging from the organization and evolution of coordinated collective action among cells, or animals, to the dynamics of information exchange in human societies. Using an integrated experimental and theoretical approach I will address how, and why, animals exhibit highly-coordinated collective behavior. I will demonstrate new imaging and virtual reality (VR) technology that allows us to reconstruct (automatically) the dynamic, time-varying sensory networks by which social influence propagates in groups. This allows us to identify, for any instant in time, the most socially-influential individuals, to reveal the (counterintuitive) relationship between network structure and social contagion, and to predict the magnitude of complex behavioural cascades within groups before they actually occur. By investigating the coupling between spatial and information dynamics in groups we also demonstrate that emergent problem solving is the predominant mechanism by which mobile groups sense, and respond to complex environmental gradients. Finally I will reveal the critical role uninformed, or unbiased, individuals play in effecting fast, democratic consensus decision-making in collectives, and will test these predictions with experiments involving schooling fish and wild baboons, as well as suggest how such results may relate to decision-making in neural systems.