פרסומים

Protein aggregation correlates with many human diseases. Protein aggregates differ in structure and shape. Strategies to develop effective aggregation inhibitors that reach the clinic failed so far. Here, we developed a family of peptides targeting early aggregation stages for both amorphous and fibrillar aggregates of proteins unrelated in sequence and structure. They act on dynamic precursors before mechanistic differentiation takes place. Using peptide arrays, we first identified peptides inhibiting the amorphous aggregation of a molten globular, aggregation-prone mutant of the Axin tumor suppressor. Optimization revealed that the peptides activity did not depend on their sequences but rather on their molecular determinants: a composition of 20–30 % flexible, 30–40 % aliphatic and 20–30 % aromatic residues, a hydrophobicity/hydrophilicity ratio close to 1, and an even distribution of residues of different nature throughout the sequence. The peptides also suppressed fibrillation of Tau, a disordered protein that forms amyloids in Alzheimer's disease, and slowed down that of Huntingtin Exon1, an amyloidogenic protein in Huntington's disease, both entirely unrelated to Axin. Our compounds thus target early stages of different aggregation mechanisms, inhibiting both amorphous and amyloid aggregation. Such cross-mechanistic, multi-targeting aggregation inhibitors may be lead compounds for developing drug candidates against various protein aggregation diseases.

Do negative economic shocks heighten public opposition to immigration, and through what mechanisms? Extant research suggests that economic circumstances and levels of labour market competition have little bearing on citizens' immigration attitudes. Yet personal economic shocks have the potential to trigger the threatened, anti-immigration responses – possibly through channels other than labour market competition – that prior cross-sectional research has been unable to detect. To examine these propositions, we used a unique panel study which tracked a large, population-based sample of Americans between 2007 and 2020. We found that adverse economic shocks, especially job losses, spurred opposition to unauthorized immigration. However, such effects are not concentrated among those most likely to face labour market competition from unauthorized immigrants. Instead, they are concentrated among white male Americans. This evidence suggests that the respondents' anti-immigration turn does not stem from economic concerns alone. Instead, personal experiences with the economy are refracted through salient socio-political lenses.

Phytoplankton are a major source of primary productivity. Their photosynthetic fluorescence are unique measures of their type, physiological state, and response to environmental conditions. Changes in phytoplankton photophysiology are commonly monitored by bulk fluorescence spectroscopy, where gradual changes are reported in response to different perturbations, such as light intensity changes. What is the meaning of such trends in bulk parameters if their values report ensemble averages of multiple unsynchronized cells? To answer this, we developed an experimental scheme that enables tracking fluorescence intensities, brightnesses, and their ratios, as well as mean photon nanotimes equivalent to mean fluorescence lifetimes, one cell at a time. We monitored three different phytoplankton species during diurnal cycles and in response to an abrupt increase in light intensity. Our results show that we can define specific subpopulations of cells by their fluorescence parameters for each of the phytoplankton species, and in response to varying light conditions. Importantly, we identify the cells undergo well-defined transitions between these subpopulations. The approach shown in this work will be useful in the exact characterization of phytoplankton cell states and parameter signatures in response to different changes these cells experience in marine environments, which will be applicable for monitoring marine-related environmental effects.

Sensitive spectroscopic analyses of molecular systems are being revolutionized utilizing the broad, equidistant spectra of frequency combs. Recently, photonically integrated frequency combs have emerged through low-power continuous laser pumping of microring resonators, resulting in stable, low-power, and compact frequency combs. Additional important photonic building blocks are plasmonic resonators, which allow exceptional sensitivity to their environment, forming the backbone of many spectroscopic biosensing experiments. However, coupling microcombs with plasmonic systems remains unexplored. Here, we demonstrate the integration of a photonic-circuit-based frequency comb with a water-cladded prism-based plasmonic resonator, enabling compact, broadband direct microcomb plasmonic spectroscopy. Our plasmonic-microcomb cavity-enhanced platform demonstrates high sensitivity and multidimensionality, opening avenues for a range of coherent, broadband, linear, and nonlinear chemical and biosensing applications.

Between early summer 1540 and the new year of 1541, Alexander Nowell composed the only surviving Latin letter from England to Sir Thomas Wyatt. On behalf of the Dean and Chapter of Norwich Cathedral, he asks Wyatt, Sir Francis Bryan, and Henry Howard, Earl of Surrey, to help the new foundation resist the expropriation of its properties. The letter fills in several biographical lacunae for this prominent trio of courtiers.  It provides primary evidence of Wyatt’s membership and sponsorship of English humanist networks.  It offers the first sure evidence of Wyatt’s contact with Surrey, corroborating the evidence of Surrey’s poetry.  It reveals the association of Wyatt, Surrey, and Bryan with evangelical figures: Nowell, later Dean of St Paul’s, was already a central figure in Oxford reform.  And it presents an intricate example of the chains of patronage that reached, in the wake of the dissolution, across the universities, the new fleet of cathedral foundations, and the heights of the Henrician court.

We analyze whether—and, if so, how—Americans reacted to the escalation of the trade war between the United States and China in June 2018. To address this issue, we leverage surveys conducted in the United States during this phase of the economic clash. We find a significant reduction in support for Donald Trump and his trade policy immediately following the announcement of retaliatory tariffs by the Chinese government. Moreover, respondents’ economic concerns about the trade war were primarily sociotropic and only weakly related to personal pocketbook considerations or local exposure to Chinese retaliatory tariffs. We also find that the trade war’s intensification was politically consequential, decreasing support for Republican candidates in the 2018 midterm elections. Our findings indicate that trade wars can be politically costly for incumbent politicians, even among voters who are not directly affected by retaliatory tariffs.

Understanding extreme precipitation events (EPEs) and their underlying dynamical processes and moisture transport patterns is essential to mitigating EPE-related risks. In this study, we investigate the dynamics of 82 EPEs (≥100mmd-1) over the territory of Ukraine in the recent decades (1979-2019), of which the majority occurred in summer. The EPEs are identified based on precipitation observations from 215 meteorological stations and posts in Ukraine. The atmospheric variables for the case study analysis of selected EPEs and for climatological composites and trajectory calculations were taken from ERA5 reanalyses. Moisture sources contributing to the EPEs in Ukraine are identified with kinematic backward trajectories and the subsequent application of a moisture source identification scheme based on the humidity mass budget along these trajectories. The large-scale atmospheric circulation associated with EPEs was studied for a selection of representative EPEs in all seasons and with the aid of composites of all events per season. Results show that EPEs in summer occur all across Ukraine, but in other seasons EPE hotspots are mainly in the Carpathians and along the Black Sea and Sea of Azov. All EPEs were associated with a surface cyclone, with most having an upper-level trough, except for the winter events that occurred in situations with very strong westerly jets. Isentropic potential vorticity anomalies associated with EPEs in Ukraine show clear dipole structures in all seasons, however, interestingly with a different orientation of these anomaly dipoles between seasons. The analysis of moisture sources revealed a very strong case-to-case variability and often a combination of local and remote sources. Oceanic sources dominate in winter, but land evapotranspiration accounts for 60%-80% of the moisture that rains out in EPEs in the other seasons. Taken together, these findings provide a novel insight into large-scale characteristics of EPEs in Ukraine, a region with a unique geographical setting and with moisture sources as diverse as Newfoundland, the Azores, the Caspian Sea, and the Arctic Ocean.