Publications

Protein aggregation is involved in a variety of diseases, including neurodegenerative diseases and cancer. The cellular environment is crowded by a plethora of cosolutes comprising small molecules and biomacromolecules at high concentrations, which may influence the aggregation of proteins in vivo. To account for the effect of cosolutes on cancer-related protein aggregation, we studied their effect on the aggregation of the cancer-related L106R mutant of the Axin protein. Axin is a key player in the Wnt signaling pathway, and the L106R mutation in its RGS domain results in a native molten globule that tends to form native-like aggregates. This results in uncontrolled activation of the Wnt signaling pathway, leading to cancer. We monitored the aggregation process of Axin RGS L106R in vitro in the presence of a wide ensemble of cosolutes including polyols, amino acids, betaine and polyethylene glycol (PEG) crowders. Except myo-inositol, all polyols decreased RGS L106R aggregation, with carbohydrates exerting the strongest inhibition. Conversely, betaine and PEGs enhanced aggregation. These results are consistent with the reported effects of osmolytes and crowders on the stability of molten globular proteins and with both amorphous and amyloid aggregation mechanisms. We suggest a model of Axin L106R aggregation in vivo, whereby molecularly small osmolytes keep the protein as a free solublemolecule but the increased crowding of the bound state by macromolecules induces its aggregation at the nano-scale. To our knowledge, this is the first systematic study on the effect of osmolytes and crowders on a process of native-like aggregation involved in pathology, as it sheds light on the contribution of cosolutes to the onset of cancer as a protein misfolding disease, and on the relevance of aggregation in the molecular aetiology of cancer.

When Gérard Genette drew the distinction between “voice” and “focus” in narrative, he pointed to two kinds of deviation from the monitoring of narrative details based on focalization. One is “paralepsis,” that is, giving the reader more information than is available to the focal character; the other is “paralipsis” – giving the reader less information than the focal character possesses. This paper suggests that the content of paralipsis – what the focal character knows but the reader is not told – is often the intentions and concrete plans of the focal character. The paper discusses the ending of Charles Dickens’s A Tale of Two Cities (1959) as a paradigmatic case: the precise intentions of Sydney Carton are not disclosed to the reader; the second reading is therefore qualitatively different from the first reading; and the intentions of the author (the implied author or even the historical author) for this temporary gap invite interpretation and raise the issue of the reasons and the causes for this feature of the narrative as a communicative act.

Arrays of alternating metallic nanostructures present hybrid properties, which are useful for applications in photonics and catalysis. Block copolymer films provide versatile templates for fabricating periodic arrays of nanowires. Yet, creating arrays with alternating compositions or structures requires different modifications of domains of the same kind. By controlling the penetration depth of metal precursors into the film we were able to impregnate different layers of copolymer cylinders with different metals. Capitalizing on the hexagonal packing of the cylinders led to simultaneous formation of nanowires with alternating compositions and periodic arrangement on the substrate after plasma etching. Selective deposition of nanoparticles on the film enabled creating alternating bare and decorated nanowires, as well as trimetallic nanowire arrays.

Permissibility of electoral systems and in particular the conversion of a plethora of voices in the electorate to the legislature is broadly considered to depend on the number of seats per district (district magnitude) in a country. Yet the most prevalent electoral system in the democratic world, proportional representation with districts, is often characterized by an almost entirely overlooked variation: within the same country districts vary in their magnitude, sometimes by a factor of twenty. How does such variation affect permissibility of electoral systems? Drawing on a broad cross-section of democracies, we demonstrate that contrary to what the literature implicitly assumes, other things equal, a combination of large and small districts results in greater permissibility than a set of districts of similar magnitude. We find that where districts are of similar (different) magnitude the degree of permissibility is lower (higher) than that found by current literature.

Main observation and conclusion A green and efficient photolabile protecting group (PPG)-mediated glycosidation approach for the synthesis of 2-deoxy-glycosides is reported. By employing ortho-nitrobenzyl carbonate (oNBC) as PPG, N,N-dimethylformamide (DMF)-modulated SPhosAuNTf2-promoted glycosidation with per-oNBC-protected 2-deoxy-glycosyl ynenoates afforded the 2-deoxy-glycosides with moderate to excellent α-selectivities presumably depending on the reactivities of the acceptor alcohols. Based on the PPG-mediated glycosidation approach, oligosaccharides with three to six oNBC groups were effectively achieved. The multiple oNBC groups in the 2-deoxy-glycosides were completely cleaved by irradiation at 365 nm, resulting in the desired 2-deoxy-glycosides in an efficient manner without affecting the common alkyne, alkene and azide functional groups and the traditional protecting groups on the aglycones. This article is protected by copyright. All rights reserved.Main observation and conclusion A green and efficient photolabile protecting group (PPG)-mediated glycosidation approach for the synthesis of 2-deoxy-glycosides is reported. By employing ortho-nitrobenzyl carbonate (oNBC) as PPG, N,N-dimethylformamide (DMF)-modulated SPhosAuNTf2-promoted glycosidation with per-oNBC-protected 2-deoxy-glycosyl ynenoates afforded the 2-deoxy-glycosides with moderate to excellent α-selectivities presumably depending on the reactivities of the acceptor alcohols. Based on the PPG-mediated glycosidation approach, oligosaccharides with three to six oNBC groups were effectively achieved. The multiple oNBC groups in the 2-deoxy-glycosides were completely cleaved by irradiation at 365 nm, resulting in the desired 2-deoxy-glycosides in an efficient manner without affecting the common alkyne, alkene and azide functional groups and the traditional protecting groups on the aglycones. This article is protected by copyright. All rights reserved.

Political polarization on the digital sphere poses a real challenge to many democracies around the world. Although the issue has received some scholarly attention, there is a need to improve the conceptual precision in the increasingly blurry debate. The use of computational communication science approaches allows us to track political conversations in a fine-grained manner within their natural settings – the realm of interactive social media. The present study combines different algorithmic approaches to studying social media data in order to capture both the interactional structure and content of dynamic political talk online. We conducted an analysis of political polarization across social media platforms (analyzing Facebook, Twitter, and WhatsApp) over 16 months, with close to a quarter million online contributions regarding a political controversy in Israel. Our comprehensive measurement of interactive political talk enables us to address three key aspects of political polarization: (1) interactional polarization – homophilic versus heterophilic user interactions; (2) positional polarization – the positions expressed, and (3) affective polarization – the emotions and attitudes expressed. Our findings indicate that political polarization on social media cannot be conceptualized as a unified phenomenon, as there are significant cross-platform differences. While interactions on Twitter largely conform to established expectations (homophilic interaction patterns, aggravating positional polarization, pronounced inter-group hostility), on WhatsApp, de-polarization occurred over time. Surprisingly, Facebook was found to be the least homophilic platform in terms of interactions, positions, and emotions expressed. Our analysis points to key conceptual distinctions and raises important questions about the drivers and dynamics of political polarization online.

We hypothesize that polycations, such as nuclear histones, released by neutrophils COVID-19 aggravate COVID-19 by multiple mechanisms: (A) Neutralization of the electrostatic repulsion between the virus particles and the cell membrane, thereby enhancing receptor-mediated entry. (B) Binding to the virus particles, thereby inducing opsonin-mediated endocytosis. (C) Adding to the cytotoxicity, in conjunction with oxidants, cytokines and other pro-inflammatory substances secreted by cells of the innate immunity system. These effects may be alleviated by the administration of negatively charged polyanions such as heparins and heparinoids.

This study examines grocery price differentials across neighborhoods in a large metropolitan area (the city of Jerusalem, Israel). Important variation in access to affordable grocery shopping is documented using CPI data on prices and neighborhood-level credit card expenditure data. Residents of peripheral, nonaffluent neighborhoods are charged some of the highest prices in the city and yet display a low tendency to shop outside their neighborhood. In contrast, residents of affluent, centrally located neighborhoods often benefit from lower grocery prices charged in their own neighborhood while also displaying a high propensity to shop at the hard discount grocers located in the city’s commercial districts. The role of spatial frictions in shaping these patterns is studied within a structural model where households determine their shopping destination and retailers choose prices. The estimated model implies strong spatial segmentation in households’ demand.  Counterfactual analyses reveal that alleviating spatial frictions results in considerable benefits to the average resident of the peripheral neighborhoods. At the same time, it barely affects the equilibrium prices charged across the city, and so it does little to benefit  households with limited mobility.