Ubiquitous formation of bulk Dirac cones and topological surface states from a single orbital manifold in transition-metal dichalcogenides

Bahramy, M.&nbsp,S.,Clark, O.&nbsp,J.,Yang, B.-J.,Feng, J.,Bawden, L.,Riley, J.&nbsp,M.,Marković,, I.,Mazzola, F.,Sunko, V.,Biswas, D.,Cooil, S.&nbsp,P.,Jorge, M.,Wells, J.&nbsp,W.,Leandersson, M Nature Publishing Group, a division of Macmillan P 2018 NATURE MATERIALS Vol.17 No.1

Transition-metal dichalcogenides (TMDs) are renowned for their rich and varied bulk properties, while their single-layer variants have become one of the most prominent examples of two-dimensional materials beyond graphene. Their disparate ground states largely depend on transition metal d-electron-derived electronic states, on which the vast majority of attention has been concentrated to date. Here, we focus on the chalcogen-derived states. From density-functional theory calculations together with spin- and angle-resolved photoemission, we find that these generically host a co-existence of type-I and type-II three-dimensional bulk Dirac fermions as well as ladders of topological surface states and surface resonances. We demonstrate how these naturally arise within a single p-orbital manifold as a general consequence of a trigonal crystal field, and as such can be expected across a large number of compounds. Already, we demonstrate their existence in six separate TMDs, opening routes to tune, and ultimately exploit, their topological physics.

Crystal structure of xenotropic murine leukaemia virus-related virus (XMRV) ribonuclease H

Kim, Ju&nbsp,Hee,Kang, Sunghyun,Jung, Suk-Kyeong,Yu, Keum&nbsp,Ran,Chung, Sang&nbsp,J.,Chung, Bong&nbsp,Hyun,Erikson, Raymond&nbsp,L.,Kim, Bo&nbsp,Yeon,Kim, Seung&nbsp,Jun Portland Press Ltd. 2012 Bioscience reports Vol.32 No.5

<P>RNase H (retroviral ribonuclease H) cleaves the phosphate backbone of the RNA template within an RNA/DNA hybrid to complete the synthesis of double-stranded viral DNA. In the present study we have determined the complete structure of the RNase H domain from XMRV (xenotropic murine leukaemia virus-related virus) RT (reverse transcriptase). The basic protrusion motif of the XMRV RNase H domain is folded as a short helix and an adjacent highly bent loop. Structural superposition and subsequent mutagenesis experiments suggest that the basic protrusion motif plays a role in direct binding to the major groove in RNA/DNA hybrid, as well as in establishing the co-ordination among modules in RT necessary for proper function.</P>

Chronic Virus Infection Enforces Demethylation of the Locus that Encodes PD-1 in Antigen-Specific CD8⁺ T Cells

Youngblood, Ben,Oestreich, Kenneth&nbsp,J.,Ha, Sang-Jun,Duraiswamy, Jaikumar,Akondy, Rama&nbsp,S.,West, Erin&nbsp,E.,Wei, Zhengyu,Lu, Peiyuan,Austin, James&nbsp,W.,Riley, James&nbsp,L.,Boss, Jeremy&nb Elsevier 2011 Immunity Vol.35 No.3

<P><B>Summary</B></P><P>Functionally exhausted T cells have high expression of the PD-1 inhibitory receptor, and therapies that block PD-1 signaling show promise for resolving chronic viral infections and cancer. By using human and murine systems of acute and chronic viral infections, we analyzed epigenetic regulation of PD-1 expression during CD8<SUP>+</SUP> T cell differentiation. During acute infection, naive to effector CD8<SUP>+</SUP> T cell differentiation was accompanied by a transient loss of DNA methylation of the <I>Pdcd1</I> locus that was directly coupled to the duration and strength of T cell receptor signaling. Further differentiation into functional memory cells coincided with <I>Pdcd1</I> remethylation, providing an adapted program for regulation of PD-1 expression. In contrast, the <I>Pdcd1</I> regulatory region was completely demethylated in exhausted CD8<SUP>+</SUP> T cells and remained unmethylated even when virus titers decreased. This lack of DNA remethylation leaves the <I>Pdcd1</I> locus poised for rapid expression, potentially providing a signal for premature termination of antiviral functions.</P> <P><B>Highlights</B></P><P>► <I>Pdcd1</I> locus demethylation is coupled to naive to effector CD8<SUP>+</SUP> T cell differentiation ► After <I>Pdcd1</I> remethylation, select CpGs remain unmethylated in memory CD8<SUP>+</SUP> T cells ► Exhausted virus-specific CD8<SUP>+</SUP> T cells retain an unmethylated <I>Pdcd1</I> regulatory region ► Human CD8<SUP>+</SUP> T cells specific to chronic viruses retain an unmethylated <I>PDCD1</I> locus</P>

Variable Lymphocyte Receptor Recognition of the Immunodominant Glycoprotein of <i>Bacillus anthracis</i> Spores

Kirchdoerfer, Robert&nbsp,N.,Herrin, Brantley&nbsp,R.,Han, Byung&nbsp,Woo,Turnbough Jr., Charles&nbsp,L.,Cooper Jr., Max&nbsp,D.,Wilson Jr., Ian&nbsp,A. Elsevier 2012 Structure Vol.20 No.3

<P><B>Summary</B></P><P>Variable lymphocyte receptors (VLRs) are the adaptive immune receptors of jawless fish, which evolved adaptive immunity independent of other vertebrates. In lieu of the immunoglobulin fold-based T and B cell receptors, lymphocyte-like cells of jawless fish express VLRs (VLRA, VLRB, or VLRC) composed of leucine-rich repeats and are similar to toll-like receptors (TLRs) in structure, but antibodies (VLRB) and T cell receptors (VLRA and VLRC) in function. Here, we present the structural and biochemical characterization of VLR4, a VLRB, in complex with BclA, the immunodominant glycoprotein of <I>Bacillus anthracis</I> spores. Using a combination of crystallography, mutagenesis, and binding studies, we delineate the mode of antigen recognition and binding between VLR4 and BclA, examine commonalities in VLRB recognition of antigens, and demonstrate the potential of VLR4 as a diagnostic tool for the identification of <I>B</I>. <I>anthracis</I> spores.</P> <P><B>Graphical Abstract</B></P><P><ce:figure id='dfig1'></ce:figure></P><P><B>Highlights</B></P><P>► VLRBs use their C-terminal LRRs and the LRRCT-loop to interact with antigen ► Sequence-related VLRBs exhibit differential recognition of their BclA epitopes ► VLR4 binds a conserved protein epitope, yet is specific for <I>B</I>. <I>anthracis</I> spores</P>

Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

Schunter, Celia,Welch, Megan&nbsp,J.,Ryu, Taewoo,Zhang, Huoming,Berumen, Michael&nbsp,L.,Nilsson, Gö,ran&nbsp,E.,Munday, Philip&nbsp,L.,Ravasi, Timothy Nature Publishing Group, a division of Macmillan P 2016 Nature climate change Vol.6 No.11

<P>The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt(1,2). Recent studies show that the behaviour of reef fishes is impaired at projected CO2 levels(3,4); however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO2 in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO2-tolerant and CO2-sensitive parents were reared at near-future CO2 (754 mu atm) or present-day control levels (414 mu atm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO2 and the expression of parental tolerance to high CO2 in the offspring molecular phenotype. Exposure to high CO2 resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO2 conditions. This transgenerational molecular signature suggests that individual variation in CO2 sensitivity could facilitate adaptation of fish populations to ocean acidification.</P>

Granulin Is a Soluble Cofactor for Toll-like Receptor 9 Signaling

Park, Boyoun,Buti, Ludovico,Lee, Sungwook,Matsuwaki, Takashi,Spooner, Eric,Brinkmann, Melanie&nbsp,M.,Nishihara, Masugi,Ploegh, Hidde&nbsp,L. Elsevier 2011 Immunity Vol.34 No.4

<P><B>Summary</B></P><P>Toll-like receptor (TLR) signaling plays a critical role in innate and adaptive immune responses and must be tightly controlled. TLR4 uses LPS binding protein, MD-2, and CD14 as accessories to respond to LPS. We therefore investigated the presence of an analagous soluble cofactor that might assist in the recruitment of CpG oligonucleotides (CpG-ODNs) to TLR9. We report the identification of granulin as an essential secreted cofactor that potentiates TLR9-driven responses to CpG-ODNs. Granulin, an unusual cysteine-rich protein, bound to CpG-ODNs and interacted with TLR9. Macrophages from granulin-deficient mice showed not only impaired delivery of CpG-ODNs to endolysosomal compartments, but also decreased interaction of TLR9 with CpG-ODNs. As a consequence, granulin-deficient macrophages showed reduced responses to stimulation with CpG-ODNs, a trait corrected by provision of exogenous granulin. Thus, we propose that granulin contributes to innate immunity as a critical soluble cofactor for TLR9 signaling.</P> <P><B>Highlights</B></P><P>► Granulin binds TLR9 and CpG oligonucleotides ► Granulin is sufficient for intracellular localization of CpG-ODNs ► Granulin is a critical cofactor in enabling TLR9 signal transduction</P>

antiSMASH 4.0—improvements in chemistry prediction and gene cluster boundary identification

Blin, Kai,Wolf, Thomas,Chevrette, Marc G.,Lu, Xiaowen,Schwalen, Christopher J.,Kautsar, Satria A.,Suarez&nbsp,Duran, Hernando G.,de&nbsp,los&nbsp,Santos, Emmanuel&nbsp,L. ,C.,Kim, Hyun Uk,Nave, Ma Oxford University Press 2017 Nucleic acids research Vol.45 No.w1

<P><B>Abstract</B></P><P>Many antibiotics, chemotherapeutics, crop protection agents and food preservatives originate from molecules produced by bacteria, fungi or plants. In recent years, genome mining methodologies have been widely adopted to identify and characterize the biosynthetic gene clusters encoding the production of such compounds. Since 2011, the ‘antibiotics and secondary metabolite analysis shell—antiSMASH’ has assisted researchers in efficiently performing this, both as a web server and a standalone tool. Here, we present the thoroughly updated antiSMASH version 4, which adds several novel features, including prediction of gene cluster boundaries using the ClusterFinder method or the newly integrated CASSIS algorithm, improved substrate specificity prediction for non-ribosomal peptide synthetase adenylation domains based on the new SANDPUMA algorithm, improved predictions for terpene and ribosomally synthesized and post-translationally modified peptides cluster products, reporting of sequence similarity to proteins encoded in experimentally characterized gene clusters on a per-protein basis and a domain-level alignment tool for comparative analysis of <I>trans</I>-AT polyketide synthase assembly line architectures. Additionally, several usability features have been updated and improved. Together, these improvements make antiSMASH up-to-date with the latest developments in natural product research and will further facilitate computational genome mining for the discovery of novel bioactive molecules.</P>

Innervation Patterns of Autonomic Axons in the Human Endocrine Pancreas

Rodriguez-Diaz, Rayner,Abdulreda, Midhat&nbsp,H.,Formoso, Alexander&nbsp,L.,Gans, Itai,Ricordi, Camillo,Berggren, Per-Olof,Caicedo, Alejandro Elsevier 2011 Cell metabolism Vol.14 No.1

<P><B>Summary</B></P><P>The autonomic nervous system regulates hormone secretion from the endocrine pancreas, the islets of Langerhans, thus impacting glucose metabolism. The parasympathetic and sympathetic nerves innervate the pancreatic islet, but the precise innervation patterns are unknown, particularly in human. Here we demonstrate that the innervation of human islets is different from that of mouse islets and does not conform to existing models of autonomic control of islet function. By visualizing axons in three dimensions and quantifying axonal densities and contacts within pancreatic islets, we found that, unlike mouse endocrine cells, human endocrine cells are sparsely contacted by autonomic axons. Few parasympathetic cholinergic axons penetrate the human islet, and the invading sympathetic fibers preferentially innervate smooth muscle cells of blood vessels located within the islet. Thus, rather than modulating endocrine cell function directly, sympathetic nerves may regulate hormone secretion in human islets by controlling local blood flow or by acting on islet regions located downstream.</P> <P><B>Highlights</B></P><P>► Detailed quantitative analysis of the innervation of mouse and human islets ► Human endocrine cells are sparsely innervated ► Sympathetic axons innervate vascular smooth muscle cells deep inside human islets ► Autonomic control of human islets may use unique mechanisms</P>

Tunable room-temperature magnetic skyrmions in Ir/Fe/Co/Pt multilayers

Soumyanarayanan, Anjan,Raju, M.,Gonzalez Oyarce, A. L.,Tan, Anthony K. C.,Im, Mi-Young,Petrović,, A.&nbsp,P.,Ho, Pin,Khoo, K. H.,Tran, M.,Gan, C. K.,Ernult, F.,Panagopoulos, C. Nature Publishing Group 2017 Nature Materials Vol.16 No.9

Magnetic skyrmions are nanoscale topological spin structures offering great promise for next-generation information storage technologies. The recent discovery of sub-100-nm room-temperature (RT) skyrmions in several multilayer films has triggered vigorous efforts to modulate their physical properties for their use in devices. Here we present a tunable RT skyrmion platform based on multilayer stacks of Ir/Fe/Co/Pt, which we study using X-ray microscopy, magnetic force microscopy and Hall transport techniques. By varying the ferromagnetic layer composition, we can tailor the magnetic interactions governing skyrmion properties, thereby tuning their thermodynamic stability parameter by an order of magnitude. The skyrmions exhibit a smooth crossover between isolated (metastable) and disordered lattice configurations across samples, while their size and density can be tuned by factors of two and ten, respectively. We thus establish a platform for investigating functional sub-50-nm RT skyrmions, pointing towards the development of skyrmion-based memory devices.