Current approaches for efficient C À H bond activation are usually mediated by heterogeneous [1] or homogeneous [2] catalysts. The basis is the employment of transition metals or organometallic centers, which is pivotal for the successful attack on the targeted C À H bonds. [3] However, we have reported that it is feasible to use carbon-based nanomaterials to activate short-chain alkanes in catalytic dehydrogenation reactions [4] although relatively high reaction temperatures are required. It is of particular interest to know whether it is possible to activate CÀH bonds to get high value-added products at a moderate reaction temperatures by using cheap metal-free catalysts. To this end, an elegant approach using metal-or boron-doped carbon nitrides as catalysts [5] has been developed for the selective oxidation of allylic and benzylic hydrocarbons in organic solvents with moderate conversion. Attempts to achieve higher activity also include the application of N-alkoxysulfonyloxaziridines for the activation of C(sp 3 ) À H bonds, [6] although a complicated catalytic system for efficient reaction circulation was required.Layered carbon, that is, highly exfoliated graphitic structures containing one or a few graphene layers, [7] has an unconventional electronic structure, [8] which was speculated to have a high chemical reactivity. [9] Indeed, researchers observed that layered carbon can catalyze hydrogenation, [10] ring-opening polymerization, [11] and CÀH oxidation reaction, [12] and that it could serve as a support for metal oxide catalysts. [13] Herein we describe nitrogen-doped graphene materials that can activate the benzylic C À H bond with exceptionally high activity. The nitrogen atoms introduced are preferentially bound at graphitic sites in the carbon framework. This induces high charge and spin density at the adjacent ortho carbon, which promotes the formation of reactive oxygen species and the materials display exceptional catalytic activity even at room temperature.Firstly, we examined the oxidation of ethylbenzene in aqueous phase with tert-butyl hydroperoxide (TBHP) as the oxidant and without using catalyst. However, no obvious activity was observed by GC after a reaction time of 24 h (Table 1, entry 1). Then we used a graphene sample prepared by the arc-discharge method (referred to as Arc-C) [14] as the catalyst for this reaction. Surprisingly, Arc-C activated ethylbenzene at 353 K to generate acetophenone in 20.7 % yield (Table 1, entry 2). As Arc-C had been prepared by a directcurrent arc-discharge method with a pure graphite rod as the electrode in an NH 3 /He atmosphere, besides trace nitrogen (0.7 %), no element other than carbon was detected by elemental analysis (EA) (oxygen cannot be detected by this method). The full X-ray photoelectron spectrum showed a C content of 97.9 % and low amounts of nitrogen and oxygen of 0.9 % and 1.1 %, respectively. This promising observation suggests that it is layered carbon material itself that catalyzed the oxyfunctionalization of the hydrocarbon. As Arc-C...

consensus-based disorder predictions, and for the first time comprehensively characterized intrinsic disorder at proteomic and protein levels from all significant perspectives, including abundance, cellular localization, functional roles, evolution, and impact on structural coverage. We show that intrinsic disorder is more abundant and has a unique profile in eukaryotes. We map disorder into archaea, bacterial and eukaryotic cells, and demonstrate that it is preferentially located in some cellular compartments. Functional analysis that considers over 1,200 annotations shows that certain functions are exclusively implemented by intrinsically disordered proteins and regions, and that some of them are specific to certain domains of life. We reveal that disordered regions are often targets for various post-translational modifications, but primarily in the eukaryotes and viruses. Using a phylogenetic tree for 14 eukaryotic and 112 bacterial species, we analyzed relations between disorder, sequence conservation and evolutionary speed. We provide a complete analysis that clearly shows that intrinsic disorder is exceptionally and uniquely abundant in each domain of life. Keywords Intrinsic disorder · Intrinsically disordered proteins · Intrinsically disordered regions · Cellular localization · Post-translational modifications · Evolutionary speed IntroductionIt is now recognized that in addition to globular, transmembrane and fibrillar proteins that are known to be characterized by unique three dimensional (3D)-structure, there is another tribe of proteins, which, being biologically functional, do not have unique 3D-structures in their native Abstract Recent years witnessed increased interest in intrinsically disordered proteins and regions. These proteins and regions are abundant and possess unique structural features and a broad functional repertoire that complements ordered proteins. However, modern studies on the abundance and functions of intrinsically disordered proteins and regions are relatively limited in size and scope of their analysis. To fill this gap, we performed a broad and detailed computational analysis of over 6 million proteins from 59 archaea, 471 bacterial, 110 eukaryotic and 325 viral proteomes. We used arguably more accurate Electronic supplementary material The online version of this article (doi:10.1007/s00018-014-1661-9) contains supplementary material, which is available to authorized users. 3states under the physiologic conditions in vitro and in vivo [1][2][3][4][5]. The members of this novel tribe are known as intrinsically disordered proteins (IDPs). Their structures are defined as highly dynamic ensembles of flexible conformations, where sampling of a large portion of a polypeptide's available conformational space is allowed. Although IDPs and intrinsically disordered regions (IDRs) in proteins are devoid of stable 3D-structures, they possess crucial biological functions and play multiple important roles in living organisms. In fact, the conformational plasticity associated with intrins...

Beta-amyloid deposition is a defining feature of Alzheimer’s disease (AD). How genetic risk factors, like APOE and TREM2 , intersect with cellular responses to beta-amyloid in human tissues is not fully understood. Using single-nucleus RNA sequencing of postmortem human brain with varied APOE and TREM2 genotypes and neuropathology, we identified distinct microglia subpopulations, including a subpopulation of CD163-positive amyloid-responsive microglia (ARM) that are depleted in cases with APOE and TREM2 risk variants. We validated our single-nucleus RNA sequencing findings in an expanded cohort of AD cases demonstrating that APOE and TREM2 risk variants are associated with a significant reduction in CD163-positive amyloid-responsive microglia. Our results showcase the diverse microglial response in AD and underscore how genetic risk factors influence cellular responses to underlying pathologies.