Dimensional crossover in a layered ferromagnet detected by spin correlation driven distortions

Magneto-elastic distortions are commonly detected across magnetic long-range ordering (LRO) transitions. In principle, they are also induced by the magnetic short-range ordering (SRO) that precedes a LRO transition, which contains information about short-range correlations and energetics that are essential for understanding how LRO is established. However these distortions are difficult to resolve because the associated atomic displacements are exceedingly small and do not break symmetry. Here we demonstrate high-multipole nonlinear optical polarimetry as a sensitive and mode selective probe of SRO induced distortions using CrSiTe$_3$ as a testbed. This compound is composed of weakly bonded sheets of nearly isotropic ferromagnetically interacting spins that, in the Heisenberg limit, would individually be impeded from LRO by the Mermin-Wagner theorem. Our results show that CrSiTe$_3$ evades this law via a two-step crossover from two- to three-dimensional magnetic SRO, manifested through two successive and previously undetected totally symmetric distortions above its Curie temperature.Comment: 17 pages main text, 4 figures, 12 pages supplementary informatio

Impulse: building a smarter memory controller

Journal ArticleImpulse is a new memory system architecture that adds two important features to a traditional memory controller. First, Impulse supports application-specific optimizations through configurable physical address remapping. By remapping physical addresses, applications control how their data is accessed and cached, improving their cache and bus utilization. Second, Impulse supports prefetching at the memory controller, which can hide much of the latency of DRAM accesses. In this paper we describe the design of the Impulse architecture, and show how an Impulse memory system can be used to improve the performance of memory-bound programs. For the NAS conjugate gradient benchmark, Impulse improves performance by 67%. Because it requires no modification to processor, cache, or bus designs, Impulse can be adopted in conventional systems. In addition to scientific applications, we expect that Impulse will benefit regularly strided, memory-bound applications of commercial importance, such as database and multimedia programs

Phosphorylation of Spinophilin Modulates Its Interaction with Actin Filaments

Spinophilin is a protein phosphatase 1 (PP1)- and actin-binding protein that modulates excitatory synaptic transmission and dendritic spine morphology. We report that spinophilin is phosphorylated in vitro by protein kinase A (PKA). Phosphorylation of spinophilin was stimulated by treatment of neostriatal neurons with a dopamine D1 receptor agonist or with forskolin, consistent with spinophilin being a substrate for PKA in intact cells. Using tryptic phosphopeptide mapping, site-directed mutagenesis, and microsequencing analysis, we identified two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin. Phosphorylation of spinophilin by PKA modulated the association between spinophilin and the actin cytoskeleton. Following subcellular fractionation, unphosphorylated spinophilin was enriched in the postsynaptic density, whereas a pool of phosphorylated spinophilin was found in the cytosol. F-actin co-sedimentation and overlay analysis revealed that phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction. In contrast, the ability of spinophilin to bind to PP1 remained unchanged. Taken together, our studies suggest that phosphorylation of spinophilin by PKA modulates the anchoring of the spinophilin-PP1 complex within dendritic spines, thereby likely contributing to the efficacy and plasticity of synaptic transmission

A charge density wave-like instability in a doped spin-orbit assisted weak Mott insulator

Layered perovskite iridates realize a rare class of Mott insulators that are predicted to be strongly spin–orbit coupled analogues of the parent state of cuprate high-temperature superconductors. Recent discoveries of pseudogap, magnetic multipolar ordered6 and possible d-wave superconducting phases in doped Sr_2IrO_4 have reinforced this analogy among the single layer variants. However, unlike the bilayer cuprates, no electronic instabilities have been reported in the doped bilayer iridate Sr_3Ir_2O_7. Here we show that Sr_3Ir_2O_7 realizes a weak Mott state with no cuprate analogue by using ultrafast time-resolved optical reflectivity to uncover an intimate connection between its insulating gap and antiferromagnetism. However, we detect a subtle charge density wave-like Fermi surface instability in metallic electron doped Sr_3Ir_2O_7 at temperatures (T_(DW)) close to 200 K via the coherent oscillations of its collective modes, which is reminiscent of that observed in cuprates. The absence of any signatures of a new spatial periodicity below T_(DW) from diffraction, scanning tunnelling and photoemission based probes suggests an unconventional and possibly short-ranged nature of this density wave order

A sulfated carbohydrate epitope inhibits axon regeneration after injury

Chondroitin sulfate proteoglycans (CSPGs) represent a major barrier to regenerating axons in the central nervous system (CNS), but the structural diversity of their polysaccharides has hampered efforts to dissect the structure-activity relationships underlying their physiological activity. By taking advantage of our ability to chemically synthesize specific oligosaccharides, we demonstrate that a sugar epitope on CSPGs, chondroitin sulfate-E (CS-E), potently inhibits axon growth. Removal of the CS-E motif significantly attenuates the inhibitory activity of CSPGs on axon growth. Furthermore, CS-E functions as a protein recognition element to engage receptors including the transmembrane protein tyrosine phosphatase PTPσ, thereby triggering downstream pathways that inhibit axon growth. Finally, masking the CS-E motif using a CS-E-specific antibody reversed the inhibitory activity of CSPGs and stimulated axon regeneration in vivo. These results demonstrate that a specific sugar epitope within chondroitin sulfate polysaccharides can direct important physiological processes and provide new therapeutic strategies to regenerate axons after CNS injury

Comprehensive mapping of O-GlcNAc modification sites using a chemically cleavable tag

The post-translational modification of serine or threonine residues of proteins with a single N-acetylglucosamine monosaccharide (O-GlcNAcylation) is essential for cell survival and function. However, relatively few O-GlcNAc modification sites have been mapped due to the difficulty of enriching and detecting O-GlcNAcylated peptides from complex samples. Here we describe an improved approach to quantitatively label and enrich O-GlcNAcylated proteins for site identification. Chemoenzymatic labelling followed by copper(I)-catalysed azide–alkyne cycloaddition (CuAAC) installs a new mass spectrometry (MS)-compatible linker designed for facile purification of O-GlcNAcylated proteins from cell lysates. The linker also allows subsequent quantitative release of O-GlcNAcylated proteins for downstream MS analysis. We validate the approach by unambiguously identifying several established O-GlcNAc sites on the proteins α-crystallin and O-GlcNAc transferase (OGT), as well as discovering new, previously unreported sites on OGT. Notably, these novel sites on OGT lie in key functional domains of the protein, underscoring how this site identification method may reveal important biological insights into protein activity and regulation

Galaxy clusters at high redshift and evolution of brightest cluster galaxies

Identification of high redshift clusters is important for studies of cosmology and cluster evolution. Using photometric redshifts of galaxies, we identify 631 clusters from the Canada-France-Hawaii Telescope (CFHT) Wide field, 202 clusters from the CHFT Deep field, 187 clusters from the Cosmic Evolution Survey (COSMOS) and 737 clusters from the Spitzer Wide-area InfraRed Extragalactic survey (SWIRE) field. The redshifts of these clusters are in the range of 0.1<z<1.6. Merging these cluster samples gives 1644 clusters in the four survey fields, of which 1088 are newly identified and more than half are from the large SWIRE field. Among 228 clusters of z>1, 191 clusters are newly identified, and most of them from the SWIRE field. With this large sample of high redshift clusters, we study the color evolution of the brightest cluster galaxies (BCGs). The colors r'-z' and r^+-m_{3.6\mu m} of the BCGs are consistent with a stellar population synthesis model in which the BCGs are formed at redshift z_f>2 and evolved passively. The colors g'-z' and B-m_{3.6\mu m} of the BCGs at redshifts z>0.8 are systematically bluer than the passive evolution model for galaxy formed at z_f~2, indicating star formation in high redshift BCGs.Comment: 10 pages, 14 figures, 2 tables; added reference, corrected typos; Table 2 is available at http://zmtt.bao.ac.cn/wzl/CV_wen.ht

Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus α-synuclein and β-amyloid aggregates

Transcellular propagation of protein aggregate “seeds” has been proposed to mediate the progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We previously reported that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface, promoting cellular uptake and intracellular seeding. However, the specificity and binding mode of these protein aggregates to HSPGs remain unknown. Here, we measured direct interaction with modified heparins to determine the size and sulfation requirements for tau, α-synuclein, and β-amyloid (Aβ) aggregate binding to glycosaminoglycans (GAGs). Varying the GAG length and sulfation patterns, we next conducted competition studies with heparin derivatives in cell-based assays. Tau aggregates required a precise GAG architecture with defined sulfate moieties in the N- and 6-O-positions, whereas the binding of α-synuclein and Aβ aggregates was less stringent. To determine the genes required for aggregate uptake, we used CRISPR/Cas9 to individually knock out the major genes of the HSPG synthesis pathway in HEK293T cells. Knockouts of the extension enzymes exostosin 1 (EXT1), exostosin 2 (EXT2), and exostosin-like 3 (EXTL3), as well as N-sulfotransferase (NDST1) or 6-O-sulfotransferase (HS6ST2) significantly reduced tau uptake, consistent with our biochemical findings, and knockouts of EXT1, EXT2, EXTL3, or NDST1, but not HS6ST2 reduced α-synuclein uptake. In summary, tau aggregates display specific interactions with HSPGs that depend on GAG length and sulfate moiety position, whereas α-synuclein and Aβ aggregates exhibit more flexible interactions with HSPGs. These principles may inform the development of mechanism-based therapies to block transcellular propagation of amyloid protein–based pathologies