The random key graph is a random graph naturally associated with the random key predistribution scheme introduced by Eschenauer and Gligor in the context of wireless sensor networks (WSNs). For this ...class of random graphs, we establish a new version of a conjectured zero-one law for graph connectivity as the number of nodes becomes unboundedly large. The results reported here complement and strengthen recent work on this conjecture by Blackburn and Gerke. In particular, the results are given under conditions which are more realistic for applications to WSNs.
Although the core subunits of Polycomb group (PcG) complexes are well characterized, little is known about the dynamics of these protein complexes during cellular differentiation. We used ...quantitative interaction proteomics and genome-wide profiling to study PcG proteins in mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). We found that the stoichiometry and genome-wide binding of PRC1 and PRC2 were highly dynamic during neural differentiation. Intriguingly, we observed a downregulation and loss of PRC2 from chromatin marked with trimethylated histone H3 K27 (H3K27me3) during differentiation, whereas PRC1 was retained at these sites. Additionally, we found PRC1 at enhancer and promoter regions independently of PRC2 binding and H3K27me3. Finally, overexpression of NPC-specific PRC1 interactors in ESCs led to increased Ring1b binding to, and decreased expression of, NPC-enriched Ring1b-target genes. In summary, our integrative analyses uncovered dynamic PcG subcomplexes and their widespread colocalization with active chromatin marks during differentiation.
Abstract
Despite recent significant progress in real-time, large-area computer-generated holography, its memory requirements and computational loads will be hard to tackle for several decades to come ...with the current paradigm based on a priori calculations and bit-plane writing to a spatial light modulator. Here we experimentally demonstrate a holistic approach to serial computation and repeatable writing of computer-generated dynamic holograms without Fourier transform, using minimal amounts of computer memory. We use the ultrafast opto-magnetic recording of holographic patterns in a ferrimagnetic film with femtosecond laser pulses, driven by the on-the-fly hardware computation of a single holographic point. The intensity-threshold nature of the magnetic medium allows sub-diffraction-limited, point-by-point toggling of arbitrarily localized magnetic spots on the sample, according to the proposed circular detour-phase encoding, providing complex modulation and symmetrical suppression of upper diffractive orders and conjugated terms in holographically reconstructed 3-D images.
Intracellular signaling via the covalent attachment of different ubiquitin linkages to protein substrates is fundamental to many cellular processes. Although linkage-selective ubiquitin interactors ...have been studied on a case-by-case basis, proteome-wide analyses have not been conducted yet. Here, we present ubiquitin interactor affinity enrichment-mass spectrometry (UbIA-MS), a quantitative interaction proteomics method that makes use of chemically synthesized diubiquitin to enrich and identify ubiquitin linkage interactors from crude cell lysates. UbIA-MS reveals linkage-selective diubiquitin interactions in multiple cell types. For example, we identify TAB2 and TAB3 as novel K6 diubiquitin interactors and characterize UCHL3 as a K27-linkage selective interactor that regulates K27 polyubiquitin chain formation in cells. Additionally, we show a class of monoubiquitin and K6 diubiquitin interactors whose binding is induced by DNA damage. We expect that our proteome-wide diubiquitin interaction landscape and established workflows will have broad applications in the ongoing efforts to decipher the complex language of ubiquitin signaling.
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•UbIA-MS enables proteome-wide profiling of ubiquitin signaling interactors•Resource of ubiquitin linkage-selective interactors in multiple cell types•The inter-UIM region determines selective binding to K48 and K63 ubiquitin linkages•Deubiquitinase UCHL3 selectively binds to and regulates K27 ubiquitin linkages
Zhang et al. report UbIA-MS, a mass-spectrometry-based proteomics workflow to comprehensively study interactions between proteins and ubiquitin linkages, based on in vitro pull-downs with chemically synthesized diubiquitins. Their work reports a rich resource of linkage-selective as well as general ubiquitin interactors in different cell types and upon cellular perturbation.
Interaction proteomics studies have provided fundamental insights into multimeric biomolecular assemblies and cell-scale molecular networks. Significant recent developments in mass spectrometry-based ...interaction proteomics have been fueled by rapid advances in label-free, isotopic, and isobaric quantitation workflows. Here, we report a quantitative protein-DNA and protein-nucleosome binding assay that uses affinity purifications from nuclear extracts coupled with isobaric chemical labeling and mass spectrometry to quantify apparent binding affinities proteome-wide. We use this assay with a variety of DNA and nucleosome baits to quantify apparent binding affinities of monomeric and multimeric transcription factors and chromatin remodeling complexes.
As a measure of the brain's temporal fine-tuning capacity, temporal resolution power (TRP) explained repeatedly a substantial amount of variance in psychometric intelligence. Recently, spatial ...suppression, referred to as the increasing difficulty in quickly perceiving motion direction as the size of the moving stimulus increases, has attracted particular attention, when it was found to be positively related to psychometric intelligence. Due to the conceptual similarities of TRP and spatial suppression, the present study investigated their mutual interplay in the relation to psychometric intelligence in 273 young adults to better understand the reasons for these relationships. As in previous studies, psychometric intelligence was positively related to a latent variable representing TRP but, in contrast to previous reports, negatively to latent and manifest measures of spatial suppression. In a combined structural equation model, TRP still explained a substantial amount of variance in psychometric intelligence while the negative relation between spatial suppression and intelligence was completely explained by TRP. Thus, our findings confirmed TRP to be a robust predictor of psychometric intelligence but challenged the assumption of spatial suppression as a representation of general information processing efficiency as reflected in psychometric intelligence. Possible reasons for the contradictory findings on the relation between spatial suppression and psychometric intelligence are discussed.
Genome-wide association studies (GWAS) have identified ~20 melanoma susceptibility loci, most of which are not functionally characterized. Here we report an approach integrating massively-parallel ...reporter assays (MPRA) with cell-type-specific epigenome and expression quantitative trait loci (eQTL) to identify susceptibility genes/variants from multiple GWAS loci. From 832 high-LD variants, we identify 39 candidate functional variants from 14 loci displaying allelic transcriptional activity, a subset of which corroborates four colocalizing melanocyte cis-eQTL genes. Among these, we further characterize the locus encompassing the HIV-1 restriction gene, MX2 (Chr21q22.3), and validate a functional intronic variant, rs398206. rs398206 mediates the binding of the transcription factor, YY1, to increase MX2 levels, consistent with the cis-eQTL of MX2 in primary human melanocytes. Melanocyte-specific expression of human MX2 in a zebrafish model demonstrates accelerated melanoma formation in a BRAF
background. Our integrative approach streamlines GWAS follow-up studies and highlights a pleiotropic function of MX2 in melanoma susceptibility.
We investigate the secure connectivity of wireless sensor networks under the random pairwise key predistribution scheme of Chan, Perrig, and Song. Unlike recent work carried out under the assumption ...of full visibility, here we assume a (simplified) communication model where unreliable wireless links are represented as independent on/off channels. We present conditions on how to scale the model parameters so that the network 1) has no secure node that is isolated and 2) is securely connected, both with high probability, when the number of sensor nodes becomes large. The results are given in the form of zero-one laws, and exhibit significant differences with corresponding results in the full-visibility case. Through simulations, these zero-one laws are shown to also hold under a more realistic communication model, namely the disk model.
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