bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthy dietary indices and risk of depressive outcomes: a
systematic review and meta-analysis of observational studies
Authors: Lassale Camille , Batty G. David , Baghdadli Amaria , Jacka Felice , Sánchez-Villegas Almudena , Kivimäki Mika , Akbaraly Tasnime
Published: September 2018

With depression being the psychiatric disorder incurring the largest
societal costs in developed countries, there is a need to gather evidence on the
role of nutrition in depression, to help develop recommendations and guide future
psychiatric health care. The aim of this systematic review was to synthesize the
link between diet quality, measured using a range of predefined indices, and
depressive outcomes. Medline, Embase and PsychInfo were searched up to
31st May 2018 for studies that examined adherence to a
healthy diet in relation to depressive symptoms or clinical depression. Where
possible, estimates were pooled using random effect meta-analysis with
stratification by observational study design and dietary score. A total of 20
longitudinal and 21 cross-sectional studies were included. These studies utilized an
array of dietary measures, including: different measures of adherence to the
Mediterranean diet, the Healthy Eating Index (HEI) and Alternative HEI (AHEI), the
Dietary Approaches to Stop Hypertension, and the Dietary Inflammatory Index. The
most compelling evidence was found for the Mediterranean diet and incident
depression, with a combined relative risk estimate of highest vs. lowest adherence
category from four longitudinal studies of 0.67 (95% CI 0.55–0.82). A lower Dietary
Inflammatory Index was also associated with lower depression incidence in four
longitudinal studies (relative risk 0.76; 95% CI: 0.63–0.92). There were fewer
longitudinal studies using other indices, but they and cross-sectional evidence also
suggest an inverse association between healthy diet and depression (e.g., relative
risk 0.65; 95% CI 0.50–0.84 for HEI/AHEI). To conclude, adhering to a healthy diet,
in particular a traditional Mediterranean diet, or avoiding a pro-inflammatory diet
appears to confer some protection against depression in observational studies. This
provides a reasonable evidence base to assess the role of dietary interventions to
prevent depression. This systematic review was registered in the PROSPERO
International Prospective Register of Systematic Reviews under the number
CRD42017080579.
Increased inflammation and brain glutamate define a subtype of depression with decreased regional homogeneity, impaired network integrity, and anhedonia
Authors: Haroon Ebrahim , Chen Xiangchuan , Li Zhihao , Patel Thrusharth , Woolwine Bobbi J. , Hu Xiaoping P. , Felger Jennifer C. , Miller Andrew H.
Published: September 2018

Combined increases in peripheral inflammation and brain glutamate may identify a subtype of depression with distinct neuroimaging signatures. Two contrasting subgroups of depressed subjects—with and without combined elevations in plasma C-reactive protein (CRP) and basal ganglia glutamate (high and low CRP-Glu, respectively) were identified by hierarchical clustering using plasma CRP (indexing peripheral inflammation) and magnetic resonance spectroscopy (MRS)-based measurement of left basal ganglia glutamate. High CRP-Glu group status was associated with greater severity of anhedonia and cognitive and motor slowing. Local- and network-level measures of functional integrity were determined using brain oxygen level-dependent (BOLD)-oscillatory activity and graph theory. Greater decreases in concordance of oscillatory activity between neighboring voxels (Regional Homogeneity ‘ReHo’,p < 0.01) within the MRS volume-of-interest was associated with the High CRP-Glu subgroup. Using brain-wide, CRP-Glu ReHo contrast maps, a covariance network of 41 regions-of-interest (ROIs) with similar ReHo decreases was identified in the High CRP-Glu group and was located to brain structures previously implicated in depression. The 41-ROI network was further decomposed into four subnetworks. ReHo decreases within Subnetwork4—comprised of reward processing regions —was associated with anhedonia. Subnetwork4 ReHo also predicted decreased network integrity, which mediated the link between local ReHo and anhedonia in the Low but not High CRP-Glu group. These findings suggest that decreased ReHo and related disruptions in network integrity may reflect toxic effects of inflammation-induced increases in extrasynaptic glutamate signaling. Moreover, local BOLD oscillatory activity as reflected in ReHo might be a useful measure of target-engagement in the brain for treatment of inflammation-induced behaviors.
Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation
Authors: Luijk René , Wu Haoyu , Ward-Caviness Cavin K , Hannon Eilis , Carnero-Montoro Elena , Min Josine L. , Mandaviya Pooja , Müller-Nurasyid Martina , Mei Hailiang , van der Maarel Silvere M. ,   BIOS Consortium, Beekman Marian , der Breggen Ruud van , Deelen Joris , Lakenberg Nico , Moed Matthijs , Suchiman H. Eka D. , Arindrarto Wibowo , van’t Hof Peter , Jan Bonder Marc , Deelen Patrick , Tigchelaar Ettje F. , Zhernakova Alexandra , Zhernakova Dasha V. , van Dongen Jenny , Hottenga Jouke J. , Pool René , Isaacs Aaron , Hofman Bert A. , Jhamai Mila , van der Kallen Carla J. H. , Schalkwijk Casper G. , Stehouwer Coen D. A. , van den Berg Leonard H. , van Galen Michiel , Vermaat Martijn , van Rooij Jeroen , Uitterlinden André G. , Verbiest Michael , Verkerk Marijn , Kielbasa P. Szymon M. , Bot Jan , Nooren Irene , van Dijk Freerk , Swertz Morris A. , van Heemst Diana , Relton Caroline , Mill Jonathan , Waldenberger Melanie , Bell Jordana T. , Jansen Rick , Zhernakova Alexandra , Franke Lude , ‘t Hoen Peter A. C. , Boomsma Dorret I. , van Duijn Cornelia M. , van Greevenbroek Marleen M. J. , Veldink Jan H. , Wijmenga Cisca , van Meurs Joyce , Daxinger Lucia , Slagboom P. Eline , van Zwet Erik W. , Heijmans Bastiaan T.
Published: September 2018

X-chromosome inactivation (XCI), i.e., the inactivation of one of the female X chromosomes, restores equal expression of X-chromosomal genes between females and males. However, ~10% of genes show variable degrees of escape from XCI between females, although little is known about the causes of variable XCI. Using a discovery data-set of 1867 females and 1398 males and a replication sample of 3351 females, we show that genetic variation at three autosomal loci is associated with female-specific changes in X-chromosome methylation. Through cis-eQTL expression analysis, we map these loci to the genes SMCHD1/METTL4, TRIM6/HBG2, and ZSCAN9. Low-expression alleles of the loci are predominantly associated with mild hypomethylation of CpG islands near genes known to variably escape XCI, implicating the autosomal genes in variable XCI. Together, these results suggest a genetic basis for variable escape from XCI and highlight the potential of a population genomics approach to identify genes involved in XCI.
Implementation and benchmarking of a novel analytical framework to clinically evaluate tumor-specific fluorescent tracers
Authors: Koller Marjory , Qiu Si-Qi , Linssen Matthijs D. , Jansen Liesbeth , Kelder Wendy , de Vries Jakob , Kruithof Inge , Zhang Guo-Jun , Robinson Dominic J. , Nagengast Wouter B. , Jorritsma-Smit Annelies , van der Vegt Bert , van Dam Gooitzen M.
Published: September 2018

During the last decade, the emerging field of molecular fluorescence imaging has led to the development of tumor-specific fluorescent tracers and an increase in early-phase clinical trials without having consensus on a standard methodology for evaluating an optical tracer. By combining multiple complementary state-of-the-art clinical optical imaging techniques, we propose a novel analytical framework for the clinical translation and evaluation of tumor-targeted fluorescent tracers for molecular fluorescence imaging which can be used for a range of tumor types and with different optical tracers. Here we report the implementation of this analytical framework and demonstrate the tumor-specific targeting of escalating doses of the near-infrared fluorescent tracer bevacizumab-800CW on a macroscopic and microscopic level. We subsequently demonstrate an 88% increase in the intraoperative detection rate of tumor-involved margins in primary breast cancer patients, indicating the clinical feasibility and support of future studies to evaluate the definitive clinical impact of fluorescence-guided surgery.
Nonreciprocal responses from non-centrosymmetric quantum materials
Authors: Tokura Yoshinori , Nagaosa Naoto
Published: September 2018

Directional transport and propagation of quantum particle and current, such as electron, photon, spin, and phonon, are known to occur in the materials system with broken inversion symmetry, as exemplified by the diode in semiconductor p–n junction and the natural optical activity in chiral materials. Such a nonreciprocal response in the quantum materials of noncentrosymmetry occurs ubiquitously when the time-reversal symmetry is further broken by applying a magnetic field or with spontaneous magnetization, such as the magnetochiral effect and the nonreciprocal magnon transport or spin current in chiral magnets. In the nonlinear regime responding to the square of current and electric field, even a more variety of nonreciprocal phenomena can show up, including the photocurrent of topological origin and the unidirectional magnetoresistance in polar/chiral semiconductors. Microscopically, these nonreciprocal responses in the quantum materials are frequently encoded by the quantum Berry phase, the toroidal moment, and the magnetoelectric monopole, thus cultivating the fertile ground of the functional topological materials. Here, we review the basic mechanisms and emergent phenomena and functions of the nonreciprocal responses in the noncentrosymmetric quantum materials.
The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice
Authors: Kindt Alida , Liebisch Gerhard , Clavel Thomas , Haller Dirk , Hörmannsperger Gabriele , Yoon Hongsup , Kolmeder Daniela , Sigruener Alexander , Krautbauer Sabrina , Seeliger Claudine , Ganzha Alexandra , Schweizer Sabine , Morisset Rosalie , Strowig Till , Daniel Hannelore , Helm Dominic , Küster Bernhard , Krumsiek Jan , Ecker Josef
Published: September 2018

Interactions between the gut microbial ecosystem and host lipid homeostasis are highly relevant to host physiology and metabolic diseases. We present a comprehensive multi-omics view of the effect of intestinal microbial colonization on hepatic lipid metabolism, integrating transcriptomic, proteomic, phosphoproteomic, and lipidomic analyses of liver and plasma samples from germfree and specific pathogen-free mice. Microbes induce monounsaturated fatty acid generation by stearoyl-CoA desaturase 1 and polyunsaturated fatty acid elongation by fatty acid elongase 5, leading to significant alterations in glycerophospholipid acyl-chain profiles. A composite classification score calculated from the observed alterations in fatty acid profiles in germfree mice clearly differentiates antibiotic-treated mice from untreated controls with high sensitivity. Mechanistic investigations reveal that acetate originating from gut microbial degradation of dietary fiber serves as precursor for hepatic synthesis of C16 and C18 fatty acids and their related glycerophospholipid species that are also released into the circulation.
Extremely rare variants reveal patterns of germline mutation rate heterogeneity in humans
Authors: Carlson Jedidiah , Locke Adam E. , Flickinger Matthew , Zawistowski Matthew , Levy Shawn , Myers Richard M. , Boehnke Michael , Kang Hyun Min , Scott Laura J. , Li Jun Z. , Zöllner Sebastian ,   The BRIDGES Consortium, Absher Devin , Akil Huda , Breen Gerome , Burmeister Margit , Cohen-Woods Sarah , Iacono William G. , Knowles James A. , Legrand Lisa , Lu Qing , McGue Matthew , McInnis Melvin G. , Pato Carlos N. , Pato Michele T. , Rivera Margarita , Sobell Janet L. , Vincent John B. , Watson Stanley J.
Published: September 2018

A detailed understanding of the genome-wide variability of single-nucleotide germline mutation rates is essential to studying human genome evolution. Here, we use ~36 million singleton variants from 3560 whole-genome sequences to infer fine-scale patterns of mutation rate heterogeneity. Mutability is jointly affected by adjacent nucleotide context and diverse genomic features of the surrounding region, including histone modifications, replication timing, and recombination rate, sometimes suggesting specific mutagenic mechanisms. Remarkably, GC content, DNase hypersensitivity, CpG islands, and H3K36 trimethylation are associated with both increased and decreased mutation rates depending on nucleotide context. We validate these estimated effects in an independent dataset of ~46,000 de novo mutations, and confirm our estimates are more accurate than previously published results based on ancestrally older variants without considering genomic features. Our results thus provide the most refined portrait to date of the factors contributing to genome-wide variability of the human germline mutation rate.
Aerosol-induced intensification of cooling effect of clouds during Indian summer monsoon
Authors: Sarangi Chandan , Kanawade Vijay P. , Tripathi Sachchida N. , Thomas Abin , Ganguly Dilip
Published: September 2018

Measurements and models show that enhanced aerosol concentrations can modify macro- and micro-physical properties of clouds. Here, we examine the effect of aerosols on continental mesoscale convective cloud systems during the Indian summer monsoon and find that these aerosol–cloud interactions have a net cooling effect at the surface and the top-of-atmosphere. Long-term (2002–2016) satellite data provide evidence of aerosol-induced cloud invigoration effect (AIvE) during the Indian summer monsoon. The AIvE leads to enhanced formation of thicker stratiform anvil clouds at higher altitudes. These AIvE-induced stratiform anvil clouds are also relatively brighter because of the presence of smaller sized ice particles. As a result, AIvE-induced increase in shortwave cloud radiative forcing is much larger than longwave cloud radiative forcing leading to the intensified net cooling effect of clouds over the Indian summer monsoon region. Such aerosol-induced cooling could subsequently decrease the surface diurnal temperature range and have significant feedbacks on lower tropospheric turbulence in a warmer and polluted future scenario.
Genome-scale metabolic reconstructions of multiple Salmonella strains reveal serovar-specific metabolic traits
Authors: Seif Yara , Kavvas Erol , Lachance Jean-Christophe , Yurkovich James T. , Nuccio Sean-Paul , Fang Xin , Catoiu Edward , Raffatellu Manuela , Palsson Bernhard O. , Monk Jonathan M.
Published: September 2018

Salmonellastrains are traditionally classified into serovars based on their surface antigens. While increasing availability of whole-genome sequences has allowed for more detailed subtyping of strains, links between genotype, serovar, and host remain elusive. Here we reconstruct genome-scale metabolic models for 410Salmonellastrains spanning 64 serovars. Model-predicted growth capabilities in over 530 different environments demonstrate that: (1) theSalmonellaaccessory metabolic network includes alternative carbon metabolism, and cell wall biosynthesis; (2) metabolic capabilities correspond to each strain’s serovar and isolation host; (3) growth predictions agree with 83.1% of experimental outcomes for 12 strains (690 out of 858); (4) 27 strains are auxotrophic for at least one compound, includingl-tryptophan, niacin,l-histidine,l-cysteine, and p-aminobenzoate; and (5) the catabolic pathways that are important for fitness in the gastrointestinal environment are lost amongst extraintestinal serovars. Our results reveal growth differences that may reflect adaptation to particular colonization sites.
Microglial dopamine receptor elimination defines sex-specific nucleus accumbens development and social behavior in adolescent rats
Authors: Kopec Ashley M. , Smith Caroline J. , Ayre Nathan R. , Sweat Sean C. , Bilbo Staci D.
Published: September 2018

Adolescence is a developmental period in which the mesolimbic dopaminergic “reward” circuitry of the brain, including the nucleus accumbens (NAc), undergoes significant plasticity. Dopamine D1 receptors (D1rs) in the NAc are critical for social behavior, but how these receptors are regulated during adolescence is not well understood. In this report, we demonstrate that microglia and complement-mediated phagocytic activity shapes NAc development by eliminating D1rs in male, but not female rats, during adolescence. Moreover, immune-mediated elimination of D1rs is required for natural developmental changes in male social play behavior. These data demonstrate for the first time that microglia and complement-mediated immune signaling (i) participate in adolescent brain development in a sex-specific manner, and (ii) are causally implicated in developmental changes in behavior. These data have broad implications for understanding the adolescent critical period of development, the molecular mechanisms underlying social behavior, and sex differences in brain structure and function.
rec-YnH enables simultaneous many-by-many detection of direct protein–protein and protein–RNA interactions
Authors: Yang Jae-Seong , Garriga-Canut Mireia , Link Nele , Carolis Carlo , Broadbent Katrina , Beltran-Sastre Violeta , Serrano Luis , Maurer Sebastian P.
Published: September 2018

Knowing which proteins and RNAs directly interact is essential for understanding cellular mechanisms. Unfortunately, discovering such interactions is costly and often unreliable. To overcome these limitations, we developed rec-YnH, a new yeast two and three-hybrid-based screening pipeline capable of detecting interactions within protein libraries or between protein libraries and RNA fragment pools. rec-YnH combines batch cloning and transformation with intracellular homologous recombination to generate bait–prey fusion libraries. By developing interaction selection in liquid–gels and using an ORF sequence-based readout of interactions via next-generation sequencing, we eliminate laborious plating and barcoding steps required by existing methods. We use rec-Y2H to simultaneously map interactions of protein domains and reveal novel putative interactors of PAR proteins. We further employ rec-Y2H to predict the architecture of published coprecipitated complexes. Finally, we use rec-Y3H to map interactions between multiple RNA-binding proteins and RNAs—the first time interactions between protein and RNA pools are simultaneously detected.
A conserved glycine harboring disease-associated mutations permits NMDA receptor slow deactivation and high Ca2+ permeability
Authors: Amin Johansen B. , Leng Xiaoling , Gochman Aaron , Zhou Huan-Xiang , Wollmuth Lonnie P.
Published: September 2018

A variety of de novo and inherited missense mutations associated with neurological disorders are found in the NMDA receptor M4 transmembrane helices, which are peripheral to the pore domain in eukaryotic ionotropic glutamate receptors. Subsets of these mutations affect receptor gating with dramatic effects, including in one instance halting it, occurring at a conserved glycine near the extracellular end of M4. Functional experiments and molecular dynamic simulations of constructs with and without substitutions at this glycine indicate that it acts as a hinge, permitting the intracellular portion of the ion channel to laterally expand. This expansion stabilizes long-lived open states leading to slow deactivation and high Ca2+ permeability. Our studies provide a functional and structural framework for the effect of missense mutations on NMDARs at central synapses and highlight how the M4 segment may represent a pathway for intracellular modulation of NMDA receptor function.
Europe’s renewable energy directive poised to harm global forests
Authors: Searchinger Timothy D. , Beringer Tim , Holtsmark Bjart , Kammen Daniel M. , Lambin Eric F. , Lucht Wolfgang , Raven Peter , van Ypersele Jean-Pascal
Published: September 2018

This comment raises concerns regarding the way in which a new European directive, aimed at reaching higher renewable energy targets, treats wood harvested directly for bioenergy use as a carbon-free fuel. The result could consume quantities of wood equal to all Europe’s wood harvests, greatly increase carbon in the air for decades, and set a dangerous global example.
Proteomics reveals signal peptide features determining the client specificity in human TRAP-dependent ER protein import
Authors: Nguyen Duy , Stutz Regine , Schorr Stefan , Lang Sven , Pfeffer Stefan , Freeze Hudson H. , Förster Friedrich , Helms Volkhard , Dudek Johanna , Zimmermann Richard
Published: September 2018

In mammalian cells, one-third of all polypeptides are transported into or across the ER membrane via the Sec61 channel. While the Sec61 complex facilitates translocation of all polypeptides with amino-terminal signal peptides (SP) or transmembrane helices, the Sec61-auxiliary translocon-associated protein (TRAP) complex supports translocation of only a subset of precursors. To characterize determinants of TRAP substrate specificity, we here systematically identify TRAP-dependent precursors by analyzing cellular protein abundance changes upon TRAP depletion using quantitative label-free proteomics. The results are validated in independent experiments by western blotting, quantitative RT-PCR, and complementation analysis. The SPs of TRAP clients exhibit above-average glycine-plus-proline content and below-average hydrophobicity as distinguishing features. Thus, TRAP may act as SP receptor on the ER membrane’s cytosolic face, recognizing precursor polypeptides with SPs of high glycine-plus-proline content and/or low hydrophobicity, and triggering substrate-specific opening of the Sec61 channel through interactions with the ER-lumenal hinge of Sec61α.
Complex strain evolution of polar and magnetic order in multiferroic BiFeO3 thin films
Authors: Chen Zuhuang , Chen Zhanghui , Kuo Chang-Yang , Tang Yunlong , Dedon Liv R. , Li Qian , Zhang Lei , Klewe Christoph , Huang Yen-Lin , Prasad Bhagwati , Farhan Alan , Yang Mengmeng , Clarkson James D. , Das Sujit , Manipatruni Sasikanth , Tanaka A. , Shafer Padraic , Arenholz Elke , Scholl Andreas , Chu Ying-Hao , Qiu Z. Q. , Hu Zhiwei , Tjeng Liu-Hao , Ramesh Ramamoorthy , Wang Lin-Wang , Martin Lane W.
Published: September 2018

Electric-field control of magnetism requires deterministic control of the magnetic order and understanding of the magnetoelectric coupling in multiferroics like BiFeO3 and EuTiO3. Despite this critical need, there are few studies on the strain evolution of magnetic order in BiFeO3 films. Here, in (110)-oriented BiFeO3 films, we reveal that while the polarization structure remains relatively unaffected, strain can continuously tune the orientation of the antiferromagnetic-spin axis across a wide angular space, resulting in an unexpected deviation of the classical perpendicular relationship between the antiferromagnetic axis and the polarization. Calculations suggest that this evolution arises from a competition between the Dzyaloshinskii–Moriya interaction and single-ion anisotropy wherein the former dominates at small strains and the two are comparable at large strains. Finally, strong coupling between the BiFeO3 and the ferromagnet Co0.9Fe0.1 exists such that the magnetic anisotropy of the ferromagnet can be effectively controlled by engineering the orientation of the antiferromagnetic-spin axis.
Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5
Authors: Jenkins Meredith L. , Margaria Jean Piero , Stariha Jordan T. B. , Hoffmann Reece M. , McPhail Jacob A. , Hamelin David J. , Boulanger Martin J. , Hirsch Emilio , Burke John E.
Published: September 2018

The GTPase Rab11 plays key roles in receptor recycling, oogenesis, autophagosome formation, and ciliogenesis. However, investigating Rab11 regulation has been hindered by limited molecular detail describing activation by cognate guanine nucleotide exchange factors (GEFs). Here, we present the structure of Rab11 bound to the GEF SH3BP5, along with detailed characterization of Rab-GEF specificity. The structure of SH3BP5 shows a coiled-coil architecture that mediates exchange through a unique Rab-GEF interaction. Furthermore, it reveals a rearrangement of the switch I region of Rab11 compared with solved Rab-GEF structures, with a constrained conformation when bound to SH3BP5. Mutation of switch I provides insights into the molecular determinants that allow for Rab11 selectivity over evolutionarily similar Rab GTPases present on Rab11-positive organelles. Moreover, we show that GEF-deficient mutants of SH3BP5 show greatly decreased Rab11 activation in cellular assays of active Rab11. Overall, our results give molecular insight into Rab11 regulation, and how Rab-GEF specificity is achieved.
Modular DNA strand-displacement controllers for directing material expansion
Authors: Fern Joshua , Schulman Rebecca
Published: September 2018

Soft materials that swell or change shape in response to external stimuli show extensive promise in regenerative medicine, targeted therapeutics, and soft robotics. Generally, a stimulus for shape change must interact directly with the material, limiting the types of stimuli that may be used and necessitating high stimulus concentrations. Here, we show how DNA strand-displacement controllers within hydrogels can mediate size change by interpreting, amplifying, and integrating stimuli and releasing signals that direct the response. These controllers tune the time scale and degree of DNA-crosslinked hydrogel swelling and can actuate dramatic material size change in response to <100 nM of a specific biomolecular input. Controllers can also direct swelling in response to small molecules or perform logic. The integration of these stimuli-responsive materials with biomolecular circuits is a major step towards autonomous soft robotic systems in which sensing and actuation are implemented by biomolecular reaction networks.
New suspension-feeding radiodont suggests evolution of microplanktivory in Cambrian macronekton
Authors: Lerosey-Aubril Rudy , Pates Stephen
Published: September 2018

The rapid diversification of metazoans and their organisation in modern-style marine ecosystems during the Cambrian profoundly transformed the biosphere. What initially sparked this Cambrian explosion remains passionately debated, but the establishment of a coupling between pelagic and benthic realms, a key characteristic of modern-day oceans, might represent a primary ecological cause. By allowing the transfer of biomass and energy from the euphotic zone—the locus of primary production—to the sea floor, this biological pump would have boosted diversification within the emerging metazoan-dominated benthic communities. However, little is known about Cambrian pelagic organisms and their trophic interactions. Here we describe a filter-feeding Cambrian radiodont exhibiting morphological characters that likely enabled the capture of microplankton-sized particles, including large phytoplankton. This description of a large free-swimming suspension-feeder potentially engaged in primary consumption suggests a more direct involvement of nekton in the establishment of an oceanic pelagic-benthic coupling in the Cambrian.
Selective reduction and homologation of carbon monoxide by organometallic iron complexes
Authors: Sharpe Helen R. , Geer Ana M. , Taylor Laurence J. , Gridley Benjamin M. , Blundell Toby J. , Blake Alexander J. , Davies E. Stephen , Lewis William , McMaster Jonathan , Robinson David , Kays Deborah L.
Published: September 2018

Carbon monoxide is a key C1 feedstock for the industrial production of hydrocarbons, where it is used to make millions of tonnes of chemicals, fuels, and solvents per annum. Many transition metal complexes can coordinate CO, but the formation of new C−C bonds in well-defined compounds from the scission and subsequent coupling of two or more CO moieties at a transition metal centre remains a challenge. Herein, we report the use of low-coordinate iron(II) complexes for the selective scission and homologation of CO affording unusual squaraines and iron carboxylates at ambient temperature and pressure. A modification of the ligand framework allows for the isolation and structural characterisation of a proposed metallacyclic Fe(II) carbene intermediate. These results indicate that, with the appropriate choice of supporting ligands, it is possible to cleave and homologate carbon monoxide under mild conditions using an abundant and environmentally benign low-coordinate, first row transition metal.
Mapping a hidden terrane boundary in the mantle lithosphere with lamprophyres
Authors: Dijkstra Arjan H. , Hatch Callum
Published: September 2018

Lamprophyres represent hydrous alkaline mantle melts that are a unique source of information about the composition of continental lithosphere. Throughout southwest Britain, post-Variscan lamprophyres are (ultra)potassic with strong incompatible element enrichments. Here we show that they form two distinct groups in terms of their Sr and Nd isotopic compositions, occurring on either side of a postulated, hitherto unrecognized terrane boundary. Lamprophyres emplaced north of the boundary fall on the mantle array with εNd −1 to +1.6. Those south of the boundary are enriched in radiogenic Sr, have initial εNd values of −0.3 to −3.5, and are isotopically indistinguishable from similar-aged lamprophyres in Armorican massifs in Europe. We conclude that an Armorican terrane was juxtaposed against Avalonia well before the closure of the Variscan oceans and the formation of Pangea. The giant Cornubian Tin-Tungsten Ore Province and associated batholith can be accounted for by the fertility of Armorican lower crust and mantle lithosphere.
CD69 prevents PLZFhi innate precursors from prematurely exiting the thymus and aborting NKT2 cell differentiation
Authors: Kimura Motoko Y. , Igi Akemi , Hayashizaki Koji , Mita Yukiyoshi , Shinzawa Miho , Kadakia Tejas , Endo Yukihiro , Ogawa Satomi , Yagi Ryoji , Motohashi Shinichiro , Singer Alfred , Nakayama Toshinori
Published: September 2018

While CD69 may regulate thymocyte egress by inhibiting S1P1expression, CD69 expression is not thought to be required for normal thymocyte development. Here we show that CD69 is in fact specifically required for the differentiation of mature NKT2 cells, which do not themselves express CD69. Mechanistically, CD69 expression is required on CD24+PLZFhiinnate precursors for their retention in the thymus and completion of their differentiation into mature NKT2 cells. By contrast, CD69-deficient CD24+PLZFhiinnate precursors express S1P1and prematurely exit the thymus, while S1P1inhibitor treatment of CD69-deficient mice retains CD24+PLZFhiinnate precursors in the thymus and restores NKT2 cell differentiation. Thus, CD69 prevents S1P1expression on CD24+PLZFhiinnate precursor cells from aborting NKT2 differentiation in the thymus. This study reveals the importance of CD69 to prolong the thymic residency time of developing immature precursors for proper differentiation of a T cell subset.
Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of the anterior cingulate cortex
Authors: Zhou Haocheng , Zhang Qiaosheng , Martinez Erik , Dale Jahrane , Hu Sile , Zhang Eric , Liu Kevin , Huang Dong , Yang Guang , Chen Zhe , Wang Jing
Published: September 2018

Chronic pain is known to induce an amplified aversive reaction to peripheral nociceptive inputs. This enhanced affective response constitutes a key pathologic feature of chronic pain syndromes such as fibromyalgia. However, the neural mechanisms that underlie this important aspect of pain processing remain poorly understood, hindering the development of treatments. Here, we show that a single dose of ketamine can produce a persistent reduction in the aversive response to noxious stimuli in rodent chronic pain models, long after the termination of its anti-nociceptive effects. Furthermore, we demonstrated that this anti-aversive property is mediated by prolonged suppression of the hyperactivity of neurons in the anterior cingulate cortex (ACC), a brain region well known to regulate pain affect. Therefore, our results indicate that it is feasible to dissociate the affective from the sensory component of pain, and demonstrate the potential for low-dose ketamine to be an important therapy for chronic pain syndromes.
UPF1-like helicase grip on nucleic acids dictates processivity
Authors: Kanaan Joanne , Raj Saurabh , Decourty Laurence , Saveanu Cosmin , Croquette Vincent , Le Hir Hervé
Published: September 2018

Helicases are molecular engines which translocate along nucleic acids (NA) to unwind double-strands or remodel NA–protein complexes. While they have an essential role in genome structure and expression, the rules dictating their processivity remain elusive. Here, we developed single-molecule methods to investigate helicase binding lifetime on DNA. We found that UPF1, a highly processive helicase central to nonsense-mediated mRNA decay (NMD), tightly holds onto NA, allowing long lasting action. Conversely, the structurally similar IGHMBP2 helicase has a short residence time. UPF1 mutants with variable grip on DNA show that grip tightness dictates helicase residence time and processivity. In addition, we discovered via functional studies that a decrease in UPF1 grip impairs NMD efficiency in vivo. Finally, we propose a three-state model with bound, sliding and unbound molecular clips, that can accurately predict the modulation of helicase processivity.
Author Correction: Nanofabrication of Conductive Metallic Structures on Elastomeric Materials
Authors: Tan Edward K. W. , Rughoobur Girish , Rubio-Lara Juan , Tiwale Nikhil , Xiao Zhuocong , Davidson Colin A. B. , Lowe Christopher R. , Occhipinti Luigi G.
Published: September 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Predicting proteome dynamics using gene expression data
Authors: Kuchta Krzysztof , Towpik Joanna , Biernacka Anna , Kutner Jan , Kudlicki Andrzej , Ginalski Krzysztof , Rowicka Maga
Published: September 2018

While protein concentrations are physiologically most relevant, measuring them globally is challenging. mRNA levels are easier to measure genome-wide and hence are typically used to infer the corresponding protein abundances. The steady-state condition (assumption that protein levels remain constant) has typically been used to calculate protein concentrations, as it is mathematically convenient, even though it is often not satisfied. Here, we propose a method to estimate genome-wide protein abundances without this assumption. Instead, we assume that the system returns to its baseline at the end of the experiment, which is true for cyclic phenomena (e.g. cell cycle) and many time-course experiments. Our approach only requires availability of gene expression and protein half-life data. As proof-of-concept, we predicted proteome dynamics associated with the budding yeast cell cycle, the results are available for browsing online at http://dynprot.cent.uw.edu.pl/. The approach was validated experimentally by verifying that the predicted protein concentration changes were consistent with measurements for all proteins tested. Additionally, if proteomic data are available as well, we can also infer changes in protein half-lives in response to posttranslational regulation, as we did for Clb2, a post-translationally regulated protein. The predicted changes in Clb2 abundance are consistent with earlier observations.
Epidemiological tracing of Batrachochytrium salamandrivorans identifies widespread infection and associated mortalities in private amphibian collections
Authors: Fitzpatrick Liam D. , Pasmans Frank , Martel An , Cunningham Andrew A.
Published: September 2018

The amphibian chytrid fungus Batrachochytrium salamandrivorans (Bsal) infects newts and salamanders (urodele amphibians), in which it can cause fatal disease. This pathogen has caused dramatic fire salamander population declines in Belgium, the Netherlands and Germany since its discovery in 2010. Thought to be native to Asia, it has been hypothesised that Bsal was introduced to Europe with the importation of infected amphibians for the commercial pet trade. Following the discovery of Bsal in captive amphibians in the United Kingdom in 2015, we used contact-tracing to identify epidemiologically-linked private amphibian collections in Western Europe. Of 16 linked collections identified, animals were tested from 11 and urodeles tested positive for Bsal in seven, including the identification of the pathogen in Spain for the first time. Mortality of Bsal-positive individuals was observed in five collections. Our results indicate that Bsal is likely widespread within the private amphibian trade, at least in Europe. These findings are important for informing policy regarding Bsal control strategies.
Deep Brain Stimulation for Parkinson’s disease changes perception in the Rubber Hand Illusion
Authors: Ding Catherine , Palmer Colin J. , Hohwy Jakob , Youssef George J. , Paton Bryan , Tsuchiya Naotsugu , Stout Julie C. , Thyagarajan Dominic
Published: September 2018

Parkinson’s disease (PD) alters cortico-basal ganglia-thalamic circuitry and susceptibility to an illusion of bodily awareness, the Rubber Hand Illusion (RHI). Bodily awareness is thought to result from multisensory integration in a predominantly cortical network; the role of subcortical connections is unknown. We studied the effect of modulating cortico-subcortical circuitry on multisensory integration for bodily awareness in 24 PD patients treated with subthalamic nucleus (STN) deep brain stimulation (DBS), in comparison to 21 healthy volunteers, using the RHI experiment. Typically, synchronous visuo-tactile cues induce a false perception of touch on the rubber hand as if it were the subject’s hand, whereas asynchronous visuo-tactile cues do not. However, we found that in the asynchronous condition, patients in the off-stimulation state did not reject the RHI as strongly as healthy controls; patients’ rejection of the RHI strengthened when STN-DBS was switched on, although it remained weaker than that of controls. Patients in the off-stimulation state also misjudged the position of their hand, indicating it to be closer to the rubber hand than controls. However, STN-DBS did not affect proprioceptive judgements or subsequent arm movements altered by the perceptual effects of the illusion. Our findings support the idea that the STN and subcortical connections have a key role in multisensory integration for bodily awareness. Decision-making in multisensory bodily illusions is discussed.
Proline provides site-specific flexibility for in vivo collagen
Authors: Chow Wing Ying , Forman Chris J. , Bihan Dominique , Puszkarska Anna M. , Rajan Rakesh , Reid David G. , Slatter David A. , Colwell Lucy J. , Wales David J. , Farndale Richard W. , Duer Melinda J.
Published: September 2018

Fibrillar collagens have mechanical and biological roles, providing tissues with both tensile strength and cell binding sites which allow molecular interactions with cell-surface receptors such as integrins. A key question is: how do collagens allow tissue flexibility whilst maintaining well-defined ligand binding sites? Here we show that proline residues in collagen glycine-proline-hydroxyproline (Gly-Pro-Hyp) triplets provide local conformational flexibility, which in turn confers well-defined, low energy molecular compression-extension and bending, by employing two-dimensional 13C-13C correlation NMR spectroscopy on 13C-labelled intact ex vivo bone and in vitro osteoblast extracellular matrix. We also find that the positions of Gly-Pro-Hyp triplets are highly conserved between animal species, and are spatially clustered in the currently-accepted model of molecular ordering in collagen type I fibrils. We propose that the Gly-Pro-Hyp triplets in fibrillar collagens provide fibril “expansion joints” to maintain molecular ordering within the fibril, thereby preserving the structural integrity of ligand binding sites.
In vitro protein expression changes in RAW 264.7 cells and HUVECs treated with dialyzed coffee extract by immunoprecipitation high performance liquid chromatography
Authors: Yoon Cheol Soo , Kim Min Keun , Kim Yeon Sook , Lee Suk Keun
Published: September 2018

RAW 264.7 cells and HUVECs were compared to evaluate the effects of dialyzed coffee extract (DCE) and artificial coffee (AC). Immunoprecipitation high performance liquid chromatography (IP-HPLC) showed DCE-2.5- (equivalent to 2.5 cups of coffee a day) and DCE-5-induced protein expression that was beneficial to human health, i.e., they led to significant increases in proliferation-, immunity-, cellular protection-, antioxidant signaling-, and osteogenesis-related proteins but decreases in inflammation-, NFkB signaling-, cellular apoptosis-, and oncogenic signaling-related proteins in RAW 264.7 cells, and slight decreases in angiogenesis-related proteins in HUVECs. These protein expression changes were less frequently observed for DCE-10 treatment, while AC treatment induced very different changes in protein expression. We suggest that the favorable cellular effects of DCE were derived from minor coffee elements that were absent in AC, and that the reduced effects of DCE-10 compared with those of DCE-2.5 or DCE-5 might have been caused by greater adverse reactions to caffeine and chlorogenic acid in DCE-10 than DCE-2.5 or DCE-5. IP-HPLC results suggested that minor coffee elements in DCE might play beneficial roles in the global protein expression of proliferation-, immunity-, anti-inflammation-, cell protection-, antioxidant-, anti-apoptosis-, anti-oncogenesis-, and osteogenesis-related proteins in RAW 264.7 cells and enhance anti-angiogenic signaling in HUVECs.
A facile synthesis of Au-nanoparticles decorated PbI2 single crystalline nanosheets for optoelectronic device applications
Authors: Shkir Mohd. , Yahia I. S. , Ganesh V. , Bitla Y. , Ashraf I. M. , Kaushik Ajeet , AlFaify S.
Published: September 2018

This research communication presents a rapid and facile microwave-assisted synthesis of single crystalline nanosheets (SCNSs) of hexagonal lead iodide (PbI2) decorated with Au nanoparticles, a potential optoelectronics material. Homogeneous low dimensional AuNP decoration in PbI2 resulted in a new absorption band at ~604 nm and a shift in band gap from 3.23 to 3.00 eV. The significant enhancement of photoluminescent (PL) intensity observed in the AuNP-PbI2 SCNSs is attributed to the coupling of the localized surface plasmon resonanzce of AuNP leading to improved excitation and emission rates of PbI2-SCNSs in the region of the localized electromagnetic field. The Au-PbI2 SCNSs display a compelling increment in photoconductivity, and its fabricated photodetector showed a stable and switchable photo-response. Due to ease of synthesis and enhanced photoconductivity along with appealing PL features, Au-PbI2 SCNS has the potential to be used as a material of choice when fabricating an optoelectronic devices of high performance.
Evidence for the beneficial effect of perceptual grouping on visual working memory: an empirical study on illusory contour and a meta-analytic study
Authors: Li Jiaofeng , Qian Jiehui , Liang Fan
Published: September 2018

The capacity of visual working memory (VWM) is found to be extremely limited. Past research shows that VWM can be facilitated by Gestalt principles of grouping, however, it remains controversial whether factors like the type of Gestalt principles, the characteristics of stimuli and the nature of experimental design could affect the beneficial effect of grouping. In particular, studies have shown that perceptual grouping could improve memory performance for a feature that is relevant for grouping, but it is unclear whether the same improvement exists for a feature that is irrelevant for grouping. In this article, an empirical study and a meta-analytic study were conducted to investigate the effect of perceptual grouping on VWM. In the empirical study, we examined the grouping effect by employing a Kanizsa illusion in which memory items were grouped by illusory contour. We found that the memory performance was improved for the grouped items even though the tested feature was grouping irrelevant, and the improvement was not significantly different from the effect of grouping by physical connectedness or by solid occlusion. In the meta-analytic study, we systematically and quantitatively examined the effect of perceptual grouping on VWM by pulling the results from all eligible studies, and found that the beneficial grouping effect was robust but the magnitude of the effect can be affected by several moderators. Factors like the types of grouping methods, the duration and the layout of the memory display, and the characteristics of the tested feature moderated the grouping effect, whereas whether employing a cue or a verbal suppression task did not. Our study suggests that the underlying mechanism of the grouping benefit may be distinct with regard to grouping relevancy of the to-be-stored feature. The grouping effect on VWM may be independent of attention for a grouping relevant feature, but may rely on attentional prioritization for a grouping irrelevant feature.
Summertime Primary and Secondary Contributions to Southern Ocean Cloud Condensation Nuclei
Authors: Fossum Kirsten N. , Ovadnevaite Jurgita , Ceburnis Darius , Dall’Osto Manuel , Marullo Salvatore , Bellacicco Marco , Simó Rafel , Liu Dantong , Flynn Michael , Zuend Andreas , O’Dowd Colin
Published: September 2018

Atmospheric aerosols in clean remote oceanic regions contribute significantly to the global albedo through the formation of haze and cloud layers; however, the relative importance of ‘primary’ wind-produced sea-spray over secondary (gas-to-particle conversion) sulphate in forming marine clouds remains unclear. Here we report on marine aerosols (PM1) over the Southern Ocean around Antarctica, in terms of their physical, chemical, and cloud droplet activation properties. Two predominant pristine air masses and aerosol populations were encountered: modified continental Antarctic (cAA) comprising predominantly sulphate with minimal sea-salt contribution and maritime Polar (mP) comprising sulphate plus sea-salt. We estimate that in cAA air, 75% of the CCN are activated into cloud droplets while in mP air, 37% are activated into droplets, for corresponding peak supersaturation ranges of 0.37–0.45% and 0.19–0.31%, respectively. When realistic marine boundary layer cloud supersaturations are considered (e.g. ~0.2–0.3%), sea-salt CCN contributed 2–13% of the activated nuclei in the cAA air and 8–51% for the marine air for surface-level wind speed < 16 m s−1. At higher wind speeds, primary marine aerosol can even contribute up to 100% of the activated CCN, for corresponding peak supersaturations as high as 0.32%.