Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.Impaired protein stability or trafficking underlies diverse ion channelopathies and represents an unexploited unifying principle for developing common treatments for otherwise dissimilar diseases. Ubiquitination limits ion channel surface density, but targeting this pathway for the purposes of basic study or therapy is challenging because of its prevalent role in proteostasis. We developed engineered deubiquitinases (enDUBs) that enable selective ubiquitin chain removal from target proteins to rescue the functional expression of disparate mutant ion channels that underlie long QT syndrome (LQT) and cystic fibrosis (CF). In an LQT type 1 (LQT1) cardiomyocyte model, enDUB treatment restored delayed rectifier potassium currents and normalized action potential duration. CF-targeted enDUBs synergistically rescued common (ΔF508) and pharmacotherapy-resistant (N1303K) CF mutations when combined with the US Food and Drug Administation (FDA)-approved drugs Orkambi (lumacaftor/ivacaftor) and Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor). Altogether, targeted deubiquitination via enDUBs provides a powerful protein stabilization method that not only corrects diverse diseases caused by impaired ion channel trafficking, but also introduces a new tool for deconstructing the ubiquitin code in situ.Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.CRELD1 is a pivotal factor for heart development, the function of which is unknown in adult life. We here provide evidence that CRELD1 is an important gatekeeper of immune system homeostasis. Exploiting expression variance in large human cohorts contrasting individuals with the lowest and highest CRELD1 expression levels revealed strong phenotypic, functional and transcriptional differences, including reduced CD4+ T cell numbers. These findings were validated in T cell-specific Creld1-deficient mice. Loss of Creld1 was associated with simultaneous overactivation and increased apoptosis, resulting in a net loss of T cells with age. Creld1 was transcriptionally and functionally linked to Wnt signaling. Sunitinib solubility dmso Collectively, gene expression variance in large human cohorts combined with murine genetic models, transcriptomics and functional testing defines CRELD1 as an important modulator of immune homeostasis.Light-matter interactions that induce charge and energy transfer across interfaces form the foundation for photocatalysis1,2, energy harvesting3 and photodetection4, among other technologies. One of the most common mechanisms associated with these processes relies on carrier injection. However, the exact role of the energy transport associated with this hot-electron injection remains unclear. Plasmon-assisted photocatalytic efficiencies can improve when intermediate insulation layers are used to inhibit the charge transfer5,6 or when off-resonance excitations are employed7, which suggests that additional energy transport and thermal effects could play an explicit role even if the charge transfer is inhibited8. This provides an additional interfacial mechanism for the catalytic and plasmonic enhancement at interfaces that moves beyond the traditionally assumed physical charge injection9-12. In this work, we report on a series of ultrafast plasmonic measurements that provide a direct measure of electronic distributions, both spatially and temporally, after the optical excitation of a metal/semiconductor heterostructure. We explicitly demonstrate that in cases of strong non-equilibrium, a novel energy transduction mechanism arises at the metal/semiconductor interface. We find that hot electrons in the metal contact transfer their energy to pre-existing free electrons in the semiconductor, without an equivalent spatiotemporal transfer of charge. Further, we demonstrate that this ballistic thermal injection mechanism can be utilized as a unique means to modulate plasmonic interactions. These experimental results are well-supported by both rigorous multilayer optical modelling and first-principle ab initio calculations.Membranes are ubiquitous in nature with primary functions that include adaptive filtering and selective transport of chemical/molecular species. Being critical to cellular functions, they are also fundamental in many areas of science and technology. Of particular importance are the adaptive and programmable membranes that can change their permeability or selectivity depending on the environment. Here, we explore implementation of such biological functions in artificial membranes and demonstrate two-dimensional self-assembled heterostructures of graphene oxide and polyamine macromolecules, forming a network of ionic channels that exhibit regulated permeability of water and monovalent ions. This permeability can be tuned by a change of pH or the presence of certain ions. Unlike traditional membranes, the regulation mechanism reported here relies on specific interactions between the membranes’ internal components and ions. This allows fabrication of membranes with programmable, predetermined permeability and selectivity, governed by the choice of components, their conformation and their charging state.