bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular sled is an eleven-amino acid vehicle facilitating biochemical interactions via sliding components along DNA
Authors: Mangel Walter F. , McGrath William J. , Xiong Kan , Graziano Vito , Blainey Paul C. 
Published: February 2016

AbstractRecently, we showed the adenovirus proteinase interacts productively with its protein substrates in vitro and in vivo in nascent virus particles via one-dimensional diffusion along the viral DNA. The mechanism by which this occurs has heretofore been unknown. We show sliding of these proteins along DNA occurs on a new vehicle in molecular biology, a ‘molecular sled’ named pVIc. This 11-amino acid viral peptide binds to DNA independent of sequence. pVIc slides on DNA, exhibiting the fastest one-dimensional diffusion constant, 26±1.8 × 106 (bp)2 s−1. pVIc is a ‘molecular sled,’ because it can slide heterologous cargos along DNA, for example, a streptavidin tetramer. Similar peptides, for example, from the C terminus of β-actin or NLSIII of the p53 protein, slide along DNA. Characteristics of the ‘molecular sled’ in its milieu (virion, nucleus) have implications for how proteins in the nucleus of cells interact and imply a new form of biochemistry, one-dimensional biochemistry.
Sequential domain assembly of ribosomal protein S3 drives 40S subunit maturation
Authors: Mitterer Valentin , Murat Guillaume , Réty Stéphane , Blaud Magali , Delbos Lila , Stanborough Tamsyn , Bergler Helmut , Leulliot Nicolas , Kressler Dieter , Pertschy Brigitte 
Published: February 2016

AbstractEukaryotic ribosomes assemble by association of ribosomal RNA with ribosomal proteins into nuclear precursor particles, which undergo a complex maturation pathway coordinated by non-ribosomal assembly factors. Here, we provide functional insights into how successive structural re-arrangements in ribosomal protein S3 promote maturation of the 40S ribosomal subunit. We show that S3 dimerizes and is imported into the nucleus with its N-domain in a rotated conformation and associated with the chaperone Yar1. Initial assembly of S3 with 40S precursors occurs via its C-domain, while the N-domain protrudes from the 40S surface. Yar1 is replaced by the assembly factor Ltv1, thereby fixing the S3 N-domain in the rotated orientation and preventing its 40S association. Finally, Ltv1 release, triggered by phosphorylation, and flipping of the S3 N-domain into its final position results in the stable integration of S3. Such a stepwise assembly may represent a new paradigm for the incorporation of ribosomal proteins.
Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis
Authors: Dubin Krista , Callahan Margaret K. , Ren Boyu , Khanin Raya , Viale Agnes , Ling Lilan , No Daniel , Gobourne Asia , Littmann Eric , Huttenhower Curtis , Pamer Eric G. , Wolchok Jedd D. 
Published: February 2016

AbstractThe composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota’s composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy.
GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person
Authors: Hu Youna , Shmygelska Alena , Tran David , Eriksson Nicholas , Tung Joyce Y. , Hinds David A. 
Published: February 2016

AbstractCircadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10−18; rs9479402 near VIP, P=3.9 × 10−11; rs55694368 near PER2, P=2.6 × 10−9; rs35833281 near HCRTR2, P=3.7 × 10−9; rs11545787 near RASD1, P=1.4 × 10−8; rs11121022 near PER3, P=2.0 × 10−8; rs9565309 near FBXL3, P=3.5 × 10−8. Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies.
Joint mouse–human phenome-wide association to test gene function and disease risk
Authors: Wang Xusheng , Pandey Ashutosh K. , Mulligan Megan K. , Williams Evan G. , Mozhui Khyobeni , Li Zhengsheng , Jovaisaite Virginija , Quarles L. Darryl , Xiao Zhousheng , Huang Jinsong , Capra John A. , Chen Zugen , Taylor William L. , Bastarache Lisa , Niu Xinnan , Pollard Katherine S. , Ciobanu Daniel C. , Reznik Alexander O. , Tishkov Artem V. , Zhulin Igor B. , Peng Junmin , Nelson Stanley F. , Denny Joshua C. , Auwerx Johan , Lu Lu , Williams Robert W. 
Published: February 2016

AbstractPhenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ∼5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ∼4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets—by far the largest coherent phenome for any experimental cohort (www.genenetwork.org). We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.
Ravens attribute visual access to unseen competitors
Authors: Bugnyar Thomas , Reber Stephan A. , Buckner Cameron 
Published: February 2016

AbstractRecent studies purported to demonstrate that chimpanzees, monkeys and corvids possess a basic Theory of Mind, the ability to attribute mental states like seeing to others. However, these studies remain controversial because they share a common confound: the conspecific’s line of gaze, which could serve as an associative cue. Here, we show that ravens Corvus corax take into account the visual access of others, even when they cannot see a conspecific. Specifically, we find that ravens guard their caches against discovery in response to the sounds of conspecifics when a peephole is open but not when it is closed. Our results suggest that ravens can generalize from their own perceptual experience to infer the possibility of being seen. These findings confirm and unite previous work, providing strong evidence that ravens are more than mere behaviour-readers.
Topological nodal-line fermions in spin-orbit metal PbTaSe2
Authors: Bian Guang , Chang Tay-Rong , Sankar Raman , Xu Su-Yang , Zheng Hao , Neupert Titus , Chiu Ching-Kai , Huang Shin-Ming , Chang Guoqing , Belopolski Ilya , Sanchez Daniel S. , Neupane Madhab , Alidoust Nasser , Liu Chang , Wang BaoKai , Lee Chi-Cheng , Jeng Horng-Tay , Zhang Chenglong , Yuan Zhujun , Jia Shuang , Bansil Arun , Chou Fangcheng , Lin Hsin , Hasan M. Zahid 
Published: February 2016

AbstractTopological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.
Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum
Authors: Lu Ake T. , Hannon Eilis , Levine Morgan E. , Hao Ke , Crimmins Eileen M. , Lunnon Katie , Kozlenkov Alexey , Mill Jonathan , Dracheva Stella , Horvath Steve 
Published: February 2016

AbstractDNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the ‘epigenetic clock’. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 × 10−8) SNPs in two loci: 2p22.1 (inside gene DHX57) and 16p13.3 near gene MLST8 (a subunit of mTOR complex 1 and 2). We find that the SNP in 16p13.3 has a cis-acting effect on the expression levels of MLST8 (P=6.9 × 10−18) in most brain regions. In cerebellar samples, the SNP in 2p22.1 has a cis-effect on DHX57 (P=4.4 × 10−5). Gene sets found by our GWAS analysis of cerebellar age acceleration exhibit significant overlap with those of Alzheimer’s disease (P=4.4 × 10−15), age-related macular degeneration (P=6.4 × 10−6), and Parkinson’s disease (P=2.6 × 10−4). Overall, our results demonstrate the utility of a new paradigm for understanding aging and age-related diseases: it will be fruitful to use epigenetic tissue age as endophenotype in GWAS.
Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation
Authors: Zhou Linjiao , Holt Matthew T. , Ohashi Nami , Zhao Aishan , Müller Manuel M. , Wang Boyuan , Muir Tom W. 
Published: February 2016

AbstractUbiquitylation of histone H2B at lysine 120 (H2B-Ub), a post-translational modification first discovered in 1980, plays a critical role in diverse nuclear processes including the regulation of transcription and DNA damage repair. Herein, we use a suite of protein chemistry methods to explore how H2B-Ub stimulates hDot1L-mediated methylation of histone H3 on lysine 79 (H3K79me). By using semisynthetic ‘designer’ chromatin containing H2B-Ub bearing a site-specifically installed photocrosslinker, here we report an interaction between a functional hotspot on ubiquitin and the N-terminus of histone H2A. Our biochemical studies indicate that this interaction is required for stimulation of hDot1L activity and leads to a repositioning of hDot1L on the nucleosomal surface, which likely places the active site of the enzyme proximal to H3K79. Collectively, our data converge on a possible mechanism for hDot1L stimulation in which H2B-Ub physically ‘corrals’ the enzyme into a productive binding orientation.
Exceptional damage-tolerance of a medium-entropy alloy CrCoNi at cryogenic temperatures
Authors: Gludovatz Bernd , Hohenwarter Anton , Thurston Keli V. S. , Bei Hongbin , Wu Zhenggang , George Easo P. , Ritchie Robert O. 
Published: February 2016

AbstractHigh-entropy alloys are an intriguing new class of metallic materials that derive their properties from being multi-element systems that can crystallize as a single phase, despite containing high concentrations of five or more elements with different crystal structures. Here we examine an equiatomic medium-entropy alloy containing only three elements, CrCoNi, as a single-phase face-centred cubic solid solution, which displays strength-toughness properties that exceed those of all high-entropy alloys and most multi-phase alloys. At room temperature, the alloy shows tensile strengths of almost 1 GPa, failure strains of ∼70% and KJIc fracture-toughness values above 200 MPa m1/2; at cryogenic temperatures strength, ductility and toughness of the CrCoNi alloy improve to strength levels above 1.3 GPa, failure strains up to 90% and KJIc values of 275 MPa m1/2. Such properties appear to result from continuous steady strain hardening, which acts to suppress plastic instability, resulting from pronounced dislocation activity and deformation-induced nano-twinning.
DNA methylation profiling of primary neuroblastoma tumors using methyl-CpG-binding domain sequencing
Authors: Decock Anneleen , Ongenaert Maté , Van Criekinge Wim , Speleman Frank , Vandesompele Jo 
Published: February 2016

AbstractComprehensive genome-wide DNA methylation studies in neuroblastoma (NB), a childhood tumor that originates from precursor cells of the sympathetic nervous system, are scarce. Recently, we profiled the DNA methylome of 102 well-annotated primary NB tumors by methyl-CpG-binding domain (MBD) sequencing, in order to identify prognostic biomarker candidates. In this data descriptor, we give details on how this data set was generated and which bioinformatics analyses were applied during data processing. Through a series of technical validations, we illustrate that the data are of high quality and that the sequenced fragments represent methylated genomic regions. Furthermore, genes previously described to be methylated in NB are confirmed. As such, these MBD sequencing data are a valuable resource to further study the association of NB risk factors with the NB methylome, and offer the opportunity to integrate methylome data with other -omic data sets on the same tumor samples such as gene copy number and gene expression, also publically available.
Krypton oxides under pressure
Authors: Zaleski-Ejgierd Patryk , Lata Pawel M. 
Published: February 2016

AbstractUnder high pressure, krypton, one of the most inert elements is predicted to become sufficiently reactive to form a new class of krypton compounds; krypton oxides. Using modern ab-initio evolutionary algorithms in combination with Density Functional Theory, we predict the existence of several thermodynamically stable Kr/O species at elevated pressures. In particular, our calculations indicate that at approx. 300 GPa the monoxide, KrO, should form spontaneously and remain thermo- and dynamically stable with respect to constituent elements and higher oxides. The monoxide is predicted to form non-molecular crystals with short Kr-O contacts, typical for genuine chemical bonds.
Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential
Authors: Xu Tengfei , Fan Zheng , Li Wenxin , Dietel Barbara , Wu Yingliang , Beckmann Matthias W. , Wrosch Jana K. , Buchfelder Michael , Eyupoglu Ilker Y. , Cao Zhijian , Savaskan Nicolai E. 
Published: February 2016

AbstractBrain tumors are fast proliferating and destructive within the brain microenvironment. Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. The glioma-specific chloride ion channel represents a specific target for therapy. Chlorotoxin (CTX), a peptide derived from scorpion venom, has been shown to be specific and efficacious in blocking glioma Cl− channel activity. Here, we report on two new derivatives (termed CA4 and CTX-23) designed and generated on the basis of the peptide sequence alignments of CTX and BmKCT. The novel peptides CA4 and CTX-23 are both effective in reducing glioma cell proliferation. In addition, CTX, CA4 and CTX-23 impact on cell migration and spheroid migration. These effects are accompanied by diminished cell extensions and increased nuclear sizes. Furthermore, we found that CA4 and CTX-23 are selective with low toxicity against primary neurons and astrocytes. In the ex vivo VOGiM, which maintain the entire brain tumor microenvironment, both CTX and CA4 display anti-tumor activity and reduce tumor volume. Hence, CTX and CA4 reveal anti-angiogenic properties with endothelial and angiogenic hotspots disrupting activities. These data report on the identification of two novel CTX derivatives with multiple anti-glioma properties including anti-angiogenesis.
Deciphering the Receptor Repertoire Encoding Specific Odorants by Time-Lapse Single-Cell Array Cytometry
Authors: Suzuki Masato , Yoshimoto Nobuo , Shimono Ken , Kuroda Shun’ichi 
Published: February 2016

AbstractMammals can recognize a vast number of odorants by using olfactory receptors (ORs) known as G protein-coupled receptors. The OR gene family is one of the most diverse gene families in mammalian genomes. Because of the vast combinations of ORs and odorants, few ORs have thus far been linked to specific odorants. Here, we established a functional screening method for OR genes by using a microchamber array containing >5,400 single olfactory epithelium-derived cells from mice applied to time-lapse single-cell array cytometry. This method facilitated the prompt isolation of single olfactory sensory neurons (OSNs) responding to the odorant of interest. Subsequent single-cell RT-PCR allowed us to isolate the genes encoding respective ORs. By using volatile molecules recognized as biomarkers for lung cancers, this method could deorphanize ORs and thereby reconstitute the OR-mediated signaling cascade in HEK293T cells. Thus, our system could be applied to identify any receptor by using specific ligands in the fields of physiopathology and pharmacology.
Gene expression and proteomic analysis of shoot apical meristem transition from dormancy to activation in Cunninghamia lanceolata (Lamb.) Hook
Authors: Xu Huimin , Cao Dechang , Chen Yanmei , Wei Dongmei , Wang Yanwei , Stevenson Rebecca Ann , Zhu Yingfang , Lin Jinxing 
Published: February 2016

AbstractIn contrast to annual plants, in perennial plants, the shoot apical meristem (SAM) can undergo seasonal transitions between dormancy and activity; understanding this transition is crucial for understanding growth in perennial plants. However, little is known about the molecular mechanisms of SAM development in trees. Here, light and transmission electron microscopy revealed that evident changes in starch granules, lipid bodies and cell walls thickness of the SAM in C. lanceolata during the transition from dormancy to activation. HPLC-ESI-MS/MS analysis showed that levels of indole-3-acetic acid (IAA) increased and levels of abscisic acid (ABA) decreased from dormant to active stage. Examination of 20 genes and 132 differentially expressed proteins revealed that the expression of genes and proteins potentially involved in cell division and expansion significantly increased in the active stage, whereas those related to the abscisic acid insensitive 3(ABI3), the cytoskeleton and energy metabolism decreased in the dormant stage. These findings provide new insights into the complex mechanism of gene and protein expression and their relation to cytological and physiological changes of SAM in this coniferous species.
Dielectric singularity in hyperbolic metamaterials: the inversion point of coexisting anisotropies
Authors: Caligiuri V. , Dhama R. , Sreekanth K. V. , Strangi G. , De Luca A. 
Published: February 2016

AbstractHyperbolic Metamaterials are artificially engineered materials whose optical properties can be specifically tailored to manifest an extremely high level of anisotropy. Due to this remarkable anisotropy they represent a unique opportunity to realize effective bulk meta-structure with extraordinary optical properties in the visible range. A simultaneous dielectric singularity in the in plane permittivity, with respect to the propagation direction, has to lead to a complete sign inversion of the same permittivity for that specific visible frequency. Such a drastic phase change has been theoretically highlighted in the past as the major challenge to be overcome in order to unlock many remarkable optical properties not present artificial optical systems. In this paper we experimentally demonstrate the realization of a metal-dielectric multilayer structure showing an inversion point of coexisting anisotropies at a specified wavelength in the visible range, rising from the particular design and fabrication process. Theoretical models and numerical simulations are in very good agreement with experimental data. Ellipsometrical experiments and optical modeling demonstrate the drastic type I/type II transition. Supercollimation effect has been achieved at the inversion point of the coexisting extreme anisotropies, whereas at the epsilon near zero and pole frequency the perfect lens behavior has been observed.
Whole genome sequencing revealed host adaptation-focused genomic plasticity of pathogenic Leptospira
Authors: Xu Yinghua , Zhu Yongzhang , Wang Yuezhu , Chang Yung-Fu , Zhang Ying , Jiang Xiugao , Zhuang Xuran , Zhu Yongqiang , Zhang Jinlong , Zeng Lingbing , Yang Minjun , Li Shijun , Wang Shengyue , Ye Qiang , Xin Xiaofang , Zhao Guoping , Zheng Huajun , Guo Xiaokui , Wang Junzhi 
Published: February 2016

AbstractLeptospirosis, caused by pathogenic Leptospira spp., has recently been recognized as an emerging infectious disease worldwide. Despite its severity and global importance, knowledge about the molecular pathogenesis and virulence evolution of Leptospira spp. remains limited. Here we sequenced and analyzed 102 isolates representing global sources. A high genomic variability were observed among different Leptospira species, which was attributed to massive gene gain and loss events allowing for adaptation to specific niche conditions and changing host environments. Horizontal gene transfer and gene duplication allowed the stepwise acquisition of virulence factors in pathogenic Leptospira evolved from a recent common ancestor. More importantly, the abundant expansion of specific virulence-related protein families, such as metalloproteases-associated paralogs, were exclusively identified in pathogenic species, reflecting the importance of these protein families in the pathogenesis of leptospirosis. Our observations also indicated that positive selection played a crucial role on this bacteria adaptation to hosts. These novel findings may lead to greater understanding of the global diversity and virulence evolution of Leptospira spp.