bluuebunny/crossref_metadata_2025_split huggingface dataset:
uvCLAP is a fast and non-radioactive method to identify in vivo targets of RNA-binding proteins
Authors: Maticzka Daniel , Ilik Ibrahim Avsar , Aktas Tugce , Backofen Rolf , Akhtar Asifa 
Published: April 2018

AbstractRNA-binding proteins (RBPs) play important and essential roles in eukaryotic gene expression regulating splicing, localization, translation, and stability of mRNAs. We describe ultraviolet crosslinking and affinity purification (uvCLAP), an easy-to-use, robust, reproducible, and high-throughput method to determine in vivo targets of RBPs. uvCLAP is fast and does not rely on radioactive labeling of RNA. We investigate binding of 15 RBPs from fly, mouse, and human cells to test the method’s performance and applicability. Multiplexing of signal and control libraries enables straightforward comparison of samples. Experiments for most proteins achieve high enrichment of signal over background. A point mutation and a natural splice isoform that change the RBP subcellular localization dramatically alter target selection without changing the targeted RNA motif, showing that compartmentalization of RBPs can be used as an elegant means to generate RNA target specificity.
Quantum probe hyperpolarisation of molecular nuclear spins
Authors: Broadway David A. , Tetienne Jean-Philippe , Stacey Alastair , Wood James D. A. , Simpson David A. , Hall Liam T. , Hollenberg Lloyd C. L. 
Published: April 2018

AbstractHyperpolarisation of nuclear spins is important in overcoming sensitivity and resolution limitations of magnetic resonance imaging and nuclear magnetic resonance spectroscopy. Current hyperpolarisation techniques require high magnetic fields, low temperatures, or catalysts. Alternatively, the emergence of room temperature spin qubits has opened new pathways to achieve direct nuclear spin hyperpolarisation. Employing a microwave-free cross-relaxation induced polarisation protocol applied to a nitrogen vacancy qubit, we demonstrate quantum probe hyperpolarisation of external molecular nuclear spins to ~50% under ambient conditions, showing a single qubit increasing the polarisation of ~106 nuclear spins by six orders of magnitude over the thermal background. Results are verified against a detailed theoretical treatment, which also describes how the system can be scaled up to a universal quantum hyperpolarisation platform for macroscopic samples. Our results demonstrate the prospects for this approach to nuclear spin hyperpolarisation for molecular imaging and spectroscopy and its potential to extend beyond into other scientific areas.
Dynamical origins of heat capacity changes in enzyme-catalysed reactions
Authors: van der Kamp Marc W. , Prentice Erica J. , Kraakman Kirsty L. , Connolly Michael , Mulholland Adrian J. , Arcus Vickery L. 
Published: April 2018

AbstractHeat capacity changes are emerging as essential for explaining the temperature dependence of enzyme-catalysed reaction rates. This has important implications for enzyme kinetics, thermoadaptation and evolution, but the physical basis of these heat capacity changes is unknown. Here we show by a combination of experiment and simulation, for two quite distinct enzymes (dimeric ketosteroid isomerase and monomeric alpha-glucosidase), that the activation heat capacity change for the catalysed reaction can be predicted through atomistic molecular dynamics simulations. The simulations reveal subtle and surprising underlying dynamical changes: tightening of loops around the active site is observed, along with changes in energetic fluctuations across the whole enzyme including important contributions from oligomeric neighbours and domains distal to the active site. This has general implications for understanding enzyme catalysis and demonstrating a direct connection between functionally important microscopic dynamics and macroscopically measurable quantities.
Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating photoreceptor
Authors: Sato Keita , Yamashita Takahiro , Ohuchi Hideyo , Takeuchi Atsuko , Gotoh Hitoshi , Ono Katsuhiko , Mizuno Misao , Mizutani Yasuhisa , Tomonari Sayuri , Sakai Kazumi , Imamoto Yasushi , Wada Akimori , Shichida Yoshinori 
Published: April 2018

AbstractMost opsins are G protein-coupled receptors that utilize retinal both as a ligand and as a chromophore. Opsins’ main established mechanism is light-triggered activation through retinal 11-cis-to-all-trans photoisomerization. Here we report a vertebrate non-visual opsin that functions as a Gi-coupled retinal receptor that is deactivated by light and can thermally self-regenerate. This opsin, Opn5L1, binds exclusively to all-trans-retinal. More interestingly, the light-induced deactivation through retinal trans-to-cis isomerization is followed by formation of a covalent adduct between retinal and a nearby cysteine, which breaks the retinal-conjugated double bond system, probably at the C11 position, resulting in thermal re-isomerization to all-trans-retinal. Thus, Opn5L1 acts as a reverse photoreceptor. We conclude that, like vertebrate rhodopsin, Opn5L1 is a unidirectional optical switch optimized from an ancestral bidirectional optical switch, such as invertebrate rhodopsin, to increase the S/N ratio of the signal transduction, although the direction of optimization is opposite to that of vertebrate rhodopsin.
BEARscc determines robustness of single-cell clusters using simulated technical replicates
Authors: Severson D. T. , Owen R. P. , White M. J. , Lu X. , Schuster-Böckler B. 
Published: April 2018

AbstractSingle-cell messenger RNA sequencing (scRNA-seq) has emerged as a powerful tool to study cellular heterogeneity within complex tissues. Subpopulations of cells with common gene expression profiles can be identified by applying unsupervised clustering algorithms. However, technical variance is a major confounding factor in scRNA-seq, not least because it is not possible to replicate measurements on the same cell. Here, we present BEARscc, a tool that uses RNA spike-in controls to simulate experiment-specific technical replicates. BEARscc works with a wide range of existing clustering algorithms to assess the robustness of clusters to technical variation. We demonstrate that the tool improves the unsupervised classification of cells and facilitates the biological interpretation of single-cell RNA-seq experiments.
Designed heterogeneous palladium catalysts for reversible light-controlled bioorthogonal catalysis in living cells
Authors: Wang Faming , Zhang Yan , Du Zhi , Ren Jinsong , Qu Xiaogang 
Published: April 2018

AbstractAs a powerful tool for chemical biology, bioorthogonal chemistry broadens the ways to explore the mystery of life. In this field, transition metal catalysts (TMCs) have received much attention because TMCs can rapidly catalyze chemical transformations that cannot be accomplished by bio-enzymes. However, fine controlling chemical reactions in living systems like bio-enzymes is still a great challenge. Herein, we construct a versatile light-controlled bioorthogonal catalyst by modifying macroporous silica-Pd0 with supramolecular complex of azobenzene (Azo) and β-cyclodextrin (CD). Its catalytic activity can be regulated by light-induced structural changes, mimicking allosteric regulation mechanism of bio-enzymes. The light-gated heterogeneous TMCs are important for in situ controlling bioorthogonal reactions and have been successfully used to synthesize a fluorescent probe for cell imaging and mitochondria-specific targeting agent by Suzuki–Miyaura cross-coupling reaction. Endowing the bioorthogonal catalyst with new functions is highly valuable for realizing more complex researches in biochemistry.
The role of CSF1R-dependent macrophages in control of the intestinal stem-cell niche
Authors: Sehgal Anuj , Donaldson David S. , Pridans Clare , Sauter Kristin A. , Hume David A. , Mabbott Neil A. 
Published: April 2018

AbstractColony-stimulating factor 1 (CSF1) controls the growth and differentiation of macrophages.CSF1R signaling has been implicated in the maintenance of the intestinal stem cell niche and differentiation of Paneth cells, but evidence of expression of CSF1R within the crypt is equivocal. Here we show that CSF1R-dependent macrophages influence intestinal epithelial differentiation and homeostasis. In the intestinal lamina propria CSF1R mRNA expression is restricted to macrophages which are intimately associated with the crypt epithelium, and is undetectable in Paneth cells. Macrophage ablation following CSF1R blockade affects Paneth cell differentiation and leads to a reduction ofLgr5+intestinal stem cells. The disturbances to the crypt caused by macrophage depletion adversely affect the subsequent differentiation of intestinal epithelial cell lineages. Goblet cell density is enhanced, whereas the development of M cells in Peyer’s patches is impeded. We suggest that modification of the phenotype or abundance of macrophages in the gut wall alters the development of the intestinal epithelium and the ability to sample gut antigens.
Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation
Authors: Marteil Gaëlle , Guerrero Adan , Vieira André F. , de Almeida Bernardo P. , Machado Pedro , Mendonça Susana , Mesquita Marta , Villarreal Beth , Fonseca Irina , Francia Maria E. , Dores Katharina , Martins Nuno P. , Jana Swadhin C. , Tranfield Erin M. , Barbosa-Morais Nuno L. , Paredes Joana , Pellman David , Godinho Susana A. , Bettencourt-Dias Mónica 
Published: April 2018

AbstractCentrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs in cancer and was shown to trigger tumorigenesis in mice. However, the incidence, consequence and origins of this abnormality are poorly understood. Here, we screened the NCI-60 panel of human cancer cell lines to systematically analyse centriole number and structure. Our screen shows that centriole amplification is widespread in cancer cell lines and highly prevalent in aggressive breast carcinomas. Moreover, we identify another recurrent feature of cancer cells: centriole size deregulation. Further experiments demonstrate that severe centriole over-elongation can promote amplification through both centriole fragmentation and ectopic procentriole formation. Furthermore, we show that overly long centrioles form over-active centrosomes that nucleate more microtubules, a known cause of invasiveness, and perturb chromosome segregation. Our screen establishes centriole amplification and size deregulation as recurrent features of cancer cells and identifies novel causes and consequences of those abnormalities.
Compositional heterogeneity near the base of the mantle transition zone beneath Hawaii
Authors: Yu Chunquan , Day Elizabeth A. , de Hoop Maarten V. , Campillo Michel , Goes Saskia , Blythe Rachel A. , van der Hilst Robert D. 
Published: April 2018

AbstractGlobal seismic discontinuities near 410 and 660 km depth in Earth’s mantle are expressions of solid-state phase transitions. These transitions modulate thermal and material fluxes across the mantle and variations in their depth are often attributed to temperature anomalies. Here we use novel seismic array analysis of SS waves reflecting off the 410 and 660 below the Hawaiian hotspot. We find amplitude–distance trends in reflectivity that imply lateral variations in wavespeed and density contrasts across 660 for which thermodynamic modeling precludes a thermal origin. No such variations are found along the 410. The inferred 660 contrasts can be explained by mantle composition varying from average (pyrolitic) mantle beneath Hawaii to a mixture with more melt-depleted harzburgite southeast of the hotspot. Such compositional segregation was predicted, from petrological and numerical convection studies, to occur near hot deep mantle upwellings like the one often invoked to cause volcanic activity on Hawaii.
Beclin1 restricts RNA virus infection in plants through suppression and degradation of the viral polymerase
Authors: Li Fangfang , Zhang Changwei , Li Yinzi , Wu Guanwei , Hou Xilin , Zhou Xueping , Wang Aiming 
Published: April 2018

AbstractAutophagy emerges as an essential immunity defense against intracellular pathogens. Here we report that turnip mosaic virus (TuMV) infection activates autophagy in plants and that Beclin1 (ATG6), a core component of autophagy, inhibits virus replication. Beclin1 interacts with NIb, the RNA-dependent RNA polymerase (RdRp) of TuMV, via the highly conserved GDD motif and the interaction complex is targeted for autophagic degradation likely through the adaptor protein ATG8a. Beclin1-mediated NIb degradation is inhibited by autophagy inhibitors. Deficiency of Beclin1 or ATG8a enhances NIb accumulation and promotes viral infection and vice versa. These data suggest that Beclin1 may be a selective autophagy receptor. Overexpression of a Beclin1 truncation mutant that binds to NIb but lacks the ability to mediate NIb degradation also inhibits virus replication. The Beclin1–RdRp interaction further extends to several RNA viruses. Thus Beclin1 restricts viral infection through suppression and also likely autophagic degradation of the viral RdRp.
A vaccinia-based single vector construct multi-pathogen vaccine protects against both Zika and chikungunya viruses
Authors: Prow Natalie A. , Liu Liang , Nakayama Eri , Cooper Tamara H. , Yan Kexin , Eldi Preethi , Hazlewood Jessamine E. , Tang Bing , Le Thuy T. , Setoh Yin Xiang , Khromykh Alexander A , Hobson-Peters Jody , Diener Kerrilyn R. , Howley Paul M. , Hayball John D. , Suhrbier Andreas 
Published: April 2018

AbstractZika and chikungunya viruses have caused major epidemics and are transmitted by Aedes aegypti and/or Aedes albopictus mosquitoes. The “Sementis Copenhagen Vector” (SCV) system is a recently developed vaccinia-based, multiplication-defective, vaccine vector technology that allows manufacture in modified CHO cells. Herein we describe a single-vector construct SCV vaccine that encodes the structural polyprotein cassettes of both Zika and chikungunya viruses from different loci. A single vaccination of mice induces neutralizing antibodies to both viruses in wild-type and IFNAR−/− mice and protects against (i) chikungunya virus viremia and arthritis in wild-type mice, (ii) Zika virus viremia and fetal/placental infection in female IFNAR−/− mice, and (iii) Zika virus viremia and testes infection and pathology in male IFNAR−/− mice. To our knowledge this represents the first single-vector construct, multi-pathogen vaccine encoding large polyproteins, and offers both simplified manufacturing and formulation, and reduced “shot burden” for these often co-circulating arboviruses.
The RNA-binding protein ARPP21 controls dendritic branching by functionally opposing the miRNA it hosts
Authors: Rehfeld Frederick , Maticzka Daniel , Grosser Sabine , Knauff Pina , Eravci Murat , Vida Imre , Backofen Rolf , Wulczyn F. Gregory 
Published: April 2018

AbstractAbout half of mammalian miRNA genes lie within introns of protein-coding genes, yet little is known about functional interactions between miRNAs and their host genes. The intronic miRNA miR-128 regulates neuronal excitability and dendritic morphology of principal neurons during mouse cerebral cortex development. Its conserved host genes, R3hdm1 and Arpp21, are predicted RNA-binding proteins. Here we use iCLIP to characterize ARPP21 recognition of uridine-rich sequences with high specificity for 3′UTRs. ARPP21 antagonizes miR-128 activity by co-regulating a subset of miR-128 target mRNAs enriched for neurodevelopmental functions. Protein–protein interaction data and functional assays suggest that ARPP21 acts as a positive post-transcriptional regulator by interacting with the translation initiation complex eIF4F. This molecular antagonism is reflected in inverse activities during dendritogenesis: miR-128 overexpression or knockdown of ARPP21 reduces dendritic complexity; ectopic ARPP21 leads to an increase. Thus, we describe a unique example of convergent function by two products of a single gene.
Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms
Authors: Zhang Yan , Ulvmar Maria H. , Stanczuk Lukas , Martinez-Corral Ines , Frye Maike , Alitalo Kari , Mäkinen Taija 
Published: April 2018

AbstractIncomplete delivery to the target cells is an obstacle for successful gene therapy approaches. Here we show unexpected effects of incomplete targeting, by demonstrating how heterogeneous inhibition of a growth promoting signaling pathway promotes tissue hyperplasia. We studied the function of the lymphangiogenic VEGFR3 receptor during embryonic and post-natal development. Inducible genetic deletion of Vegfr3 in lymphatic endothelial cells (LECs) leads to selection of non-targeted VEGFR3+ cells at vessel tips, indicating an indispensable cell-autonomous function in migrating tip cells. Although Vegfr3 deletion results in lymphatic hypoplasia in mouse embryos, incomplete deletion during post-natal development instead causes excessive lymphangiogenesis. Analysis of mosaically targeted endothelium shows that VEGFR3− LECs non-cell-autonomously drive abnormal vessel anastomosis and hyperplasia by inducing proliferation of non-targeted VEGFR3+ LECs through cell-contact-dependent reduction of Notch signaling. Heterogeneity in VEGFR3 levels thus drives vessel hyperplasia, which has implications for the understanding of mechanisms of developmental and pathological tissue growth.
Increased formate overflow is a hallmark of oxidative cancer
Authors: Meiser Johannes , Schuster Anne , Pietzke Matthias , Vande Voorde Johan , Athineos Dimitris , Oizel Kristell , Burgos-Barragan Guillermo , Wit Niek , Dhayade Sandeep , Morton Jennifer P. , Dornier Emmanuel , Sumpton David , Mackay Gillian M. , Blyth Karen , Patel Ketan J. , Niclou Simone P. , Vazquez Alexei 
Published: April 2018

AbstractFormate overflow coupled to mitochondrial oxidative metabolism\ has been observed in cancer cell lines, but whether that takes place in the tumor microenvironment is not known. Here we report the observation of serine catabolism to formate in normal murine tissues, with a relative rate correlating with serine levels and the tissue oxidative state. Yet, serine catabolism to formate is increased in the transformed tissue of in vivo models of intestinal adenomas and mammary carcinomas. The increased serine catabolism to formate is associated with increased serum formate levels. Finally, we show that inhibition of formate production by genetic interference reduces cancer cell invasion and this phenotype can be rescued by exogenous formate. We conclude that increased formate overflow is a hallmark of oxidative cancers and that high formate levels promote invasion via a yet unknown mechanism.
Model evidence for a seasonal bias in Antarctic ice cores
Authors: Erb Michael P. , Jackson Charles S. , Broccoli Anthony J. , Lea David W. , Valdes Paul J. , Crucifix Michel , DiNezio Pedro N. 
Published: April 2018

AbstractMuch of the global annual mean temperature change over Quaternary glacial cycles can be attributed to slow ice sheet and greenhouse gas feedbacks, but analysis of the short-term response to orbital forcings has the potential to reveal key relationships in the climate system. In particular, obliquity and precession both produce highly seasonal temperature responses at high latitudes. Here, idealized single-forcing model experiments are used to quantify Earth’s response to obliquity, precession, CO2, and ice sheets, and a linear reconstruction methodology is used to compare these responses to long proxy records around the globe. This comparison reveals mismatches between the annual mean response to obliquity and precession in models versus the signals within Antarctic ice cores. Weighting the model-based reconstruction toward austral winter or spring reduces these discrepancies, providing evidence for a seasonal bias in ice cores.
Gender inequity in speaking opportunities at the American Geophysical Union Fall Meeting
Authors: Ford Heather L. , Brick Cameron , Blaufuss Karine , Dekens Petra S. 
Published: April 2018

AbstractImplicit and explicit biases impede the participation of women in science, technology, engineering, and mathematic (STEM) fields. Across career stages, attending conferences and presenting research are ways to spread scientific results, find job opportunities, and gain awards. Here, we present an analysis by gender of the American Geophysical Union Fall Meeting speaking opportunities from 2014 to 2016. We find that women were invited and assigned oral presentations less often than men. However, when we control for career stage, we see similar rates between women and men and women sometimes outperform men. At the same time, women elect for poster presentations more than men. Male primary conveners allocate invited abstracts and oral presentations to women less often and below the proportion of women authors. These results highlight the need to provide equal opportunity to women in speaking roles at scientific conferences as part of the overall effort to advance women in STEM.
Single-site catalyst promoters accelerate metal-catalyzed nitroarene hydrogenation
Authors: Wang Liang , Guan Erjia , Zhang Jian , Yang Junhao , Zhu Yihan , Han Yu , Yang Ming , Cen Cheng , Fu Gang , Gates Bruce C. , Xiao Feng-Shou 
Published: April 2018

AbstractAtomically dispersed supported metal catalysts are drawing wide attention because of the opportunities they offer for new catalytic properties combined with efficient use of the metals. We extend this class of materials to catalysts that incorporate atomically dispersed metal atoms as promoters. The catalysts are used for the challenging nitroarene hydrogenation and found to have both high activity and selectivity. The promoters are single-site Sn on TiO2 supports that incorporate metal nanoparticle catalysts. Represented as M/Sn-TiO2 (M = Au, Ru, Pt, Ni), these catalysts decidedly outperform the unpromoted supported metals, even for hydrogenation of nitroarenes substituted with various reducible groups. The high activity and selectivity of these catalysts result from the creation of oxygen vacancies on the TiO2 surface by single-site Sn, which leads to efficient, selective activation of the nitro group coupled with a reaction involving hydrogen atoms activated on metal nanoparticles.
ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration
Authors: Wang Jie , Zibetti Cristina , Shang Peng , Sripathi Srinivasa R. , Zhang Pingwu , Cano Marisol , Hoang Thanh , Xia Shuli , Ji Hongkai , Merbs Shannath L. , Zack Donald J. , Handa James T. , Sinha Debasish , Blackshaw Seth , Qian Jiang 
Published: April 2018

AbstractAge-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.