Humans establish public goods to provide for shared needs like safety or healthcare. Yet, public goods rely on cooperation which can break down because of free-riding incentives. Previous research... Show moreHumans establish public goods to provide for shared needs like safety or healthcare. Yet, public goods rely on cooperation which can break down because of free-riding incentives. Previous research extensively investigated how groups solve this free-rider problem but ignored another challenge to public goods provision. Namely, some individuals do not need public goods to solve the problems they share with others. We investigate how such self-reliance influences cooperation by confronting groups in a laboratory experiment with a safety problem that could be solved either cooperatively or individually. We show that self-reliance leads to a decline in cooperation. Moreover, asymmetries in self-reliance undermine social welfare and increase wealth inequality between group members. Less dependent group members often choose to solve the shared problem individually, while more dependent members frequently fail to solve the problem, leaving them increasingly poor. While self-reliance circumvents the free-rider problem, it complicates the governing of the commons. Show less
Ligand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, the accumulation and... Show moreLigand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, the accumulation and persistence of non-biodegradable micron-sized particles in liver and spleen precludes their clinical use and limits the translational potential of MPIO-based contrast agents. Here we show that ligand-targeted MPIO derived from multiple iron oxide nanoparticles may be coupled covalently through peptide linkers that are designed to be cleaved by intracellular macrophage proteases. The synthesized particles possess potential characteristics for targeted MRI contrast agents, including high relaxivity, unappreciable sedimentation, clearance from circulation and no overt toxicity. Importantly, we demonstrate that these particles are rapidly degraded both in vitro and in vivo, and that the targeted probes can be used for detection of inflammation in vivo using MRI. This approach provides a platform for molecular MRI contrast agents that is potentially more suitable for translation to humans. Show less
A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to... Show moreA hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function. Show less
Jobst, J.; Torren, A.J.H. van der; Krasovskii, E.E.; Balgley, J.; Dean, C.R.; Tromp, R.M.; Molen, S.J. van der 2016
High electron mobility is one of graphene’s key properties, exploited for applications and fundamental research alike. Highest mobility values are found in heterostructures of graphene and... Show moreHigh electron mobility is one of graphene’s key properties, exploited for applications and fundamental research alike. Highest mobility values are found in heterostructures of graphene and hexagonal boron nitride, which consequently are widely used. However, surprisingly little is known about the interaction between the electronic states of these layered systems. Rather pragmatically, it is assumed that these do not couple significantly. Here we study the unoccupied band structure of graphite, boron nitride and their heterostructures using angle-resolved reflected-electron spectroscopy. We demonstrate that graphene and boron nitride bands do not interact over a wide energy range, despite their very similar dispersions. The method we use can be generally applied to study interactions in van der Waals systems, that is, artificial stacks of layered materials. With this we can quantitatively understand the ‘chemistry of layers’ by which novel materials are created via electronic coupling between the layers they are composed of. Show less
Mattoni, G.; Zubko, P.; Maccherozzi, F.; Torren, A.J.H. van der; Boltje, D.B.; Hadjimichael, M.; ... ; Caviglia, A.D. 2016
RORγt is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases. We report the discovery of a novel allosteric binding site on the... Show moreRORγt is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases. We report the discovery of a novel allosteric binding site on the nuclear receptor RORγt. Co-crystallization of the ligand binding domain (LBD) of RORγt with a series of small-molecule antagonists demonstrates occupancy of a previously unreported allosteric binding pocket. Binding at this non-canonical site induces an unprecedented conformational reorientation of helix 12 in the RORγt LBD, which blocks cofactor binding. The functional consequence of this allosteric ligand-mediated conformation is inhibition of function as evidenced by both biochemical and cellular studies. RORγt function is thus antagonized in a manner molecularly distinct from that of previously described orthosteric RORγt ligands. This brings forward an approach to target RORγt for the treatment of Th17-mediated autoimmune diseases. The elucidation of an unprecedented modality of pharmacological antagonism establishes a mechanism for modulation of nuclear receptors. Show less
Jobst, J.; Kautz, J.; Geelen, D.; Tromp, R.M.; Molen, S.J. van der 2015
The properties of any material are fundamentally determined by its electronic band structure. Each band represents a series of allowed states inside a material, relating electron energy and... Show moreThe properties of any material are fundamentally determined by its electronic band structure. Each band represents a series of allowed states inside a material, relating electron energy and momentum. The occupied bands, that is, the filled electron states below the Fermi level, can be routinely measured. However, it is remarkably difficult to characterize the empty part of the band structure experimentally. Here, we present direct measurements of unoccupied bands of monolayer, bilayer and trilayer graphene. To obtain these, we introduce a technique based on low-energy electron microscopy. It relies on the dependence of the electron reflectivity on incidence angle and energy and has a spatial resolution ∼10 nm. The method can be easily applied to other nanomaterials such as van der Waals structures that are available in small crystals only. Show less
