Mixed-Valence Lanthanide-Activated Phosphors: Invariance of the Intervalence Charge Transfer (IVCT) Absorption Onset across the Series

This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry C, © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/10.1021/acs.jpcc.9b11084Recently, direct evidence was given for the existence of intervalence charge transfer (IVCT) states of Eu2+/Eu3+ pairs in Eu-doped fluorite hosts and their signature in absorption spectra was characterized [ J. Phys. Chem. Lett. 2019, 10, 1851]. Here we show, by means of multiconfigurational ab initio calculations, that the IVCT absorptions of all 2+/3+ mixed valence lanthanides doped in CaF2 start basically at the same energy. This is rationalized with a simplified model of IVCT absorptions. Emissions above that energy are expected to be partly or totally quenched when 2+/3+ pairs are formed. On the basis of this finding and existing calculations, we report expected IVCT absorptions of mixed valence lanthanides doped in several fluoride, oxide, and sulfide hostsThis work was partially supported by Ministerio de Economía y Competitividad, Spain (Dirección General de Investigación y Gestión del Plan Nacional de I+D+i, MAT2017-83553-P

Mechanisms of lysosomal positioning and movement

Chemical Immunolog

Moving and positioning the endolysosomal system

Chemical Immunolog

Maintaining soluble protein homeostasis between nuclear and cytoplasmic compartments across mitosis

The nuclear envelope (NE) is central to the architecture of eukaryotic cells, both as a physical barrier separating the nucleus from the cytoplasm and as gate-keeper of selective transport between them. However, in open mitosis, the NE fragments to allow for spindle formation and segregation of chromosomes, resulting in intermixing of nuclear and cytoplasmic soluble fractions. Recent studies have shed new light on the mechanisms driving reinstatement of soluble proteome homeostasis following NE reformation in daughter cells. Here, we pro-vide an overview of how mitotic cells confront this challenge to ensure continuity of basic cellular functions across generations and elaborate on the implications for the proteasome - a macromolecular machine that functions in both cytoplas-mic and nuclear compartments.Chemical Immunolog

Playing hide and seek: tumor cells in control of MHC class I antigen presentation

MHC class I (MHC-I) molecules present a blueprint of the intracellular proteome to T cells allowing them to control infection or malignant transformation. As a response, pathogens and tumor cells often downmodulate MHC-I mediated antigen presentation to escape from immune surveillance. Although the fundamental rules of antigen presentation are known in detail, the players in this system are not saturated and new modules of regulation have recently been uncovered. Here, we update the understanding of antigen presentation by MHC-I molecules and how this can be exploited by tumors to prevent exposure of the intracellular proteome. This knowledge can provide new ways to improve immune responses against tumors and pathogens.Chemical Immunolog

Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses

Human immunodeficiency virus (HIV-1 or simply HIV) induces a persistent infection, which in the absence of treatment leads to AIDS and death in almost all infected individuals. HIV infection elicits a vigorous immune response starting about 2-3 weeks post infection that can lower the amount of virus in the body, but which cannot eradicate the virus. How HIV establishes a chronic infection in the face of a strong immune response remains poorly understood. It has been shown that HIV is able to rapidly change its proteins via mutation to evade recognition by virus-specific cytotoxic T lymphocytes (CTLs). Typically, an HIV-infected patient will generate 4-12 CTL responses specific for parts of viral proteins called epitopes. Such CTL responses lead to strong selective pressure to change the viral sequences encoding these epitopes so as to avoid CTL recognition. Here we review experimental data on HIV evolution in response to CTL pressure, mathematical models developed to explain this evolution, and highlight problems associated with the data and previous modeling efforts. We show that estimates of the strength of the epitope-specific CTL response depend on the method used to fit models to experimental data and on the assumptions made regarding how mutants are generated during infection. We illustrate that allowing CTL responses to decay over time may improve the fit to experimental data and provides higher estimates of the killing efficacy of HIV-specific CTLs. We also propose a novel method for simultaneously estimating the killing efficacy of multiple CTL populations specific for different epitopes of HIV using stochastic simulations. Lastly, we show that current estimates of the efficacy at which HIV-specific CTLs clear virus-infected cells can be improved by more frequent sampling of viral sequences and by combining data on sequence evolution with experimentally measured CTL dynamics