The nuclear export protein XPO1 is overexpressed in cancer, leading to the cytoplasmic mislocalization of multiple tumor suppressor proteins. Existing XPO1-targeting agents lack selectivity and have been associated with significant toxicity. Small molecule selective inhibitors of nuclear export (SINEs) were designed that specifically inhibit XPO1. Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine residue in the cargo-binding groove of

SUMMARY Tetraspanins are commonly believed to act only as “molecular facilitators”, with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B-cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions, one lies in the N-terminal domain of CD37 in a predicted “ITIM-like” motif and mediates SHP1-dependent death whereas the second lies in a predicted “ITAM motif” in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.

This N = 173,426 social science dataset was collected through the collaborative COVIDiSTRESS Global Survey – an open science effort to improve understanding of the human experiences of the 2020 COVID-19 pandemic between 30th March and 30th May, 2020. The dataset allows a cross-cultural study of psychological and behavioural responses to the Coronavirus pandemic and associated government measures like cancellation of public functions and stay at home orders implemented in many countries. The dataset contains demographic background variables as well as measures of Asian Disease Problem, perceived stress (PSS-10), availability of social provisions (SPS-10), trust in various authorities, trust in governmental measures to contain the virus (OECD trust), personality traits (BFF-15), information behaviours, agreement with the level of government intervention, and compliance with preventive measures, along with a rich pool of exploratory variables and written experiences. A global consortium from 39 countries and regions worked together to build and translate a survey with variables of shared interests, and recruited participants in 47 languages and dialects. Raw plus cleaned data and dynamic visualizations are available.

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The present study reports a contrasting interaction behaviour of a biologically important dye, acridine orange (AOH), with a highly water soluble anionic host, based on a β-cyclodextrin (βCD) scaffold, i.e. sulfobutylether-β-cyclodextrin (SBEβCD), in comparison to native βCD. AOH shows striking modulation in its photophysical properties, representing sequential changes in the modes of interaction with increasing SBEβCD concentration. At lower SBEβCD concentrations, AOH preferentially binds in dimeric forms at the negatively charged SBEβCD portals, leading to strong fluorescence quenching. At higher SBEβCD concentrations, the dimeric dyes convert to monomeric forms and subsequently undergo both inclusion and exo complex formation with 1 : 1 stoichiometry, resulting in a large fluorescence enhancement. The intriguing observation of sequential fluorescence switch off and switch on for an AOH-SBEβCD system is clearly facilitated by the presence of butylether chains with SO end groups at the portals of SBEβCD, providing an additional ion-ion interaction and much enhanced hydrophobic interaction for cationic AOH compared to the native βCD host. To the best of our knowledge, such fluorescence off/on switching through multistep host-guest binding has not been reported so far in the literature. The present study not only provides a detailed insight into the unique binding interactions of AOH with the SBEβCD host, but the findings of this study are also expected to be useful in designing supramolecular based drug formulations, drug delivery systems, sensors, and so on.