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  • Communicating Biotech Advances: Fiction versus Reality
    Trends Biotechnol. (IF 11.126) Pub Date : 2017-11-22
    Aleksandra Małyska, Robert Bolla, Tomasz Twardowski

    Bioscience novels use selected technologies of genetic engineering and synthetic biology to create entertaining stories. These novels are usually based on scientific knowledge, but they may arouse public concerns about technology and drive public reluctance to accept innovative technologies. The scientific community must adopt more efficient communication and transparency.

    更新日期:2017-11-23
  • Using the glycan toolbox for pathogenic interventions and glycan immunotherapy
    Curr. Opin. Biotech. (IF 9.294) Pub Date : 2017-11-22
    RJ Eveline Li, Sandra J van Vliet, Y van Kooyk
    更新日期:2017-11-23
  • Engineering of biomolecules by bacteriophage directed evolution
    Curr. Opin. Biotech. (IF 9.294) Pub Date : 2017-11-22
    Andreas K Brödel, Mark Isalan, Alfonso Jaramillo
    更新日期:2017-11-23
  • To eat or not to eat — the metabolic flavor of ferroptosis
    Curr. Opin. Cell Biol. (IF 9.937) Pub Date : 2017-11-22
    Minghui Gao, Xuejun Jiang

    Ferroptosis is a newly defined iron-dependent, non-apoptotic mode of cell death with necrotic morphology. Distinctive from other death mechanisms, ferroptosis requires cellular iron and lipid peroxides, and is dictated by specific cellular metabolic processes. Importantly, ferroptosis has been implicated in a plethora of human diseases. This paper reviews the recent advances and outstanding questions of the field by focusing on the role of cellular metabolism in ferroptosis. The relevance of ferroptosis to disease and therapy is also discussed.

    更新日期:2017-11-23
  • Mitochondrial activity in the regulation of stem cell self-renewal and differentiation
    Curr. Opin. Cell Biol. (IF 9.937) Pub Date : 2017-11-22
    Mireille Khacho, Ruth S Slack

    Mitochondria are classically known as the essential energy producers in cells. As such, the activation of mitochondrial metabolism upon cellular differentiation was deemed a necessity to fuel the high metabolic needs of differentiated cells. However, recent studies have revealed a direct role for mitochondrial activity in the regulation of stem cell fate and differentiation. Several components of mitochondrial metabolism and respiration have now been shown to regulate different aspects of stem cell differentiation through signaling, transcriptional, proteomic and epigenetic modulations. In light of these findings mitochondrial metabolism is no longer considered a consequence of cellular differentiation, but rather a key regulatory mechanism of this process. This review will focus on recent progress that defines mitochondria as the epicenters for the regulation of stem cell fate decisions.

    更新日期:2017-11-23
  • Illuminating information transfer in signaling dynamics by optogenetics
    Curr. Opin. Cell Biol. (IF 9.937) Pub Date : 2017-11-22
    Akihiro Isomura, Ryoichiro Kageyama

    Cells receive diverse signaling cues from their environment that trigger cascades of biochemical reactions in a dynamic manner. Single-cell imaging technologies have revealed that not only molecular species but also dynamic patterns of signaling inputs determine the fates of signal-receiving cells; however it has been challenging to elucidate how such dynamic information is delivered and decoded in complex networks of inter-cellular and inter-molecular interactions. The recent development of optogenetic technology with photo-sensitive proteins has changed this situation; the combination of microscopy and optogenetics provides fruitful insights into the mechanism of dynamic information processing at the single-cell level. Here, we review recent efforts to visualize the flows of dynamic patterns in signaling pathways, which utilize methods integrating single-cell imaging and optogenetics.

    更新日期:2017-11-23
  • Methods for lineage tracing on the organism-wide level
    Curr. Opin. Cell Biol. (IF 9.937) Pub Date : 2017-11-22
    Bastiaan Spanjaard, Jan Philipp Junker

    Determining the lineage origin of cell types is a major goal in developmental biology. Furthermore, lineage tracing is a powerful approach for understanding the origin of developmental defects as well as the origin of diseases such as cancer. There is now a variety of complementary approaches for identifying lineage relationships, ranging from direct observation of cell divisions by light microscopy to genetic labeling of cells using inducible recombinases and fluorescent reporters. A recent development, and the main topic of this review article, is the use of high-throughput sequencing data for lineage analysis. This emerging approach holds the promise of increased multiplexing capacity, allowing lineage analysis of large cell numbers up to the organism-wide level combined with simultaneous transcription profiling by single cell RNA sequencing.

    更新日期:2017-11-23
  • Lineage divergence of activity-driven transcription and evolution of cognitive ability
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-11-23
    Giles E. Hardingham, Priit Pruunsild, Michael E. Greenberg, Hilmar Bading

    Lineage divergence of activity-driven transcription and evolution of cognitive ability Lineage divergence of activity-driven transcription and evolution of cognitive ability, Published online: 23 November 2017; doi:10.1038/nrn.2017.138 Activity-driven changes in gene transcription regulate synaptic development and function. Bading and colleagues describe recent evidence of lineage-specific changes in the gene regulatory regions that govern excitation–transcription coupling and consider how such changes may have contributed to the evolution of human cognitive abilities.

    更新日期:2017-11-23
  • Neuromodulation: On the alert
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-11-23
    Katherine Whalley

    Neuromodulation: On the alert Neuromodulation: On the alert, Published online: 23 November 2017; doi:10.1038/nrn.2017.148 A method that integrates whole-brain neural activity measurements with cellular-level molecular phenotyping is used to investigate the neuronal populations that modulate a global brain state.

    更新日期:2017-11-23
  • Lineage divergence of activity-driven transcription and evolution of cognitive ability
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-11-23
    Giles E. Hardingham, Priit Pruunsild, Michael E. Greenberg, Hilmar Bading

    Lineage divergence of activity-driven transcription and evolution of cognitive ability Lineage divergence of activity-driven transcription and evolution of cognitive ability, Published online: 23 November 2017; doi:10.1038/nrn.2017.138 Activity-driven changes in gene transcription regulate synaptic development and function. Bading and colleagues describe recent evidence of lineage-specific changes in the gene regulatory regions that govern excitation–transcription coupling and consider how such changes may have contributed to the evolution of human cognitive abilities.

    更新日期:2017-11-23
  • Neuromodulation: On the alert
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-11-23
    Katherine Whalley

    Neuromodulation: On the alert Neuromodulation: On the alert, Published online: 23 November 2017; doi:10.1038/nrn.2017.148 A method that integrates whole-brain neural activity measurements with cellular-level molecular phenotyping is used to investigate the neuronal populations that modulate a global brain state.

    更新日期:2017-11-23
  • Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury
    Brain (IF 10.292) Pub Date : 2017-11-23
    Sara De Simoni, Peter O Jenkins, Niall J Bourke, Jessica J Fleminger, Peter J Hellyer, Amy E Jolly, Maneesh C Patel, James H Cole, Robert Leech, David J Sharp

    Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients.

    更新日期:2017-11-23
  • Nucleophilic Water Capture or Proton Loss: Single Amino Acid Switch Converts δ-Cadinene Synthase into Germacradien-4-ol Synthase
    ChemBioChem (IF 2.847) Pub Date : 2017-11-23
    Marianna Loizzi, Veronica González, David J. Miller, Rudolf K. Allemann
    更新日期:2017-11-23
  • MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Venetia Pliatsika, Phillipe Loher, Rogan Magee, Aristeidis G. Telonis, Eric Londin, Megumi Shigematsu, Yohei Kirino, Isidore Rigoutsos

    MINTbase is a repository that comprises nuclear and mitochondrial tRNA-derived fragments (‘tRFs’) found in multiple human tissues. The original version of MINTbase comprised tRFs obtained from 768 transcriptomic datasets. We used our deterministic and exhaustive tRF mining pipeline to process all of The Cancer Genome Atlas datasets (TCGA). We identified 23 413 tRFs with abundance of ≥ 1.0 reads-per-million (RPM). To facilitate further studies of tRFs by the community, we just released version 2.0 of MINTbase that contains information about 26 531 distinct human tRFs from 11 719 human datasets as of October 2017. Key new elements include: the ability to filter tRFs on-the-fly by minimum abundance thresholding; the ability to filter tRFs by tissue keywords; easy access to information about a tRF’s maximum abundance and the datasets that contain it; the ability to generate relative abundance plots for tRFs across cancer types and convert them into embeddable figures; MODOMICS information about modifications of the parental tRNA, etc. Version 2.0 of MINTbase contains 15x more datasets and nearly 4x more distinct tRFs than the original version, yet continues to offer fast, interactive access to its contents. Version 2.0 is available freely at http://cm.jefferson.edu/MINTbase/.

    更新日期:2017-11-23
  • The Planteome database: an integrated resource for reference ontologies, plant genomics and phenomics
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Laurel Cooper, Austin Meier, Marie-Angélique Laporte, Justin L. Elser, Chris Mungall, Brandon T. Sinn, Dario Cavaliere, Seth Carbon, Nathan A. Dunn, Barry Smith, Botong Qu, Justin Preece, Eugene Zhang, Sinisa Todorovic, Georgios Gkoutos, John H. Doonan, Dennis W. Stevenson, Elizabeth Arnaud, Pankaj Jaiswal

    The Planteome project (http://www.planteome.org) provides a suite of reference and species-specific ontologies for plants and annotations to genes and phenotypes. Ontologies serve as common standards for semantic integration of a large and growing corpus of plant genomics, phenomics and genetics data. The reference ontologies include the Plant Ontology, Plant Trait Ontology and the Plant Experimental Conditions Ontology developed by the Planteome project, along with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and Attribute Ontology, and others. The project also provides access to species-specific Crop Ontologies developed by various plant breeding and research communities from around the world. We provide integrated data on plant traits, phenotypes, and gene function and expression from 95 plant taxa, annotated with reference ontology terms. The Planteome project is developing a plant gene annotation platform; Planteome Noctua, to facilitate community engagement. All the Planteome ontologies are publicly available and are maintained at the Planteome GitHub site (https://github.com/Planteome) for sharing, tracking revisions and new requests. The annotated data are freely accessible from the ontology browser (http://browser.planteome.org/amigo) and our data repository.

    更新日期:2017-11-23
  • Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Patricia Casino, Laura Miguel-Romero, Juanjo Huesa, Pablo García, Francisco García-del Portillo, Alberto Marina

    The RcsCDB phosphorelay system controls an extremely large regulon in Enterobacteriaceae that involves processes such as biofilm formation, flagella production, synthesis of extracellular capsules and cell division. Therefore, fine-tuning of this system is essential for virulence in pathogenic microorganisms of this group. The final master effector of the RcsCDB system is the response regulator (RR) RcsB, which activates or represses multiple genes by binding to different promoter regions. This regulatory activity of RcsB can be done alone or in combination with additional transcriptional factors in phosphorylated or dephosphorylated states. The capacity of RcsB to interact with multiple promoters and partners, either dephosphorylated or phosphorylated, suggests an extremely conformational dynamism for this RR. To shed light on the activation mechanism of RcsB and its implication on promoter recognition, we solved the crystal structure of full-length RcsB from Salmonella enterica serovar Typhimurium in the presence and absence of a phosphomimetic molecule BeF3−. These two novel structures have guided an extensive site-directed mutagenesis study at the structural and functional level that confirms RcsB conformational plasticity and dynamism. Our data allowed us to propose a β5-T switch mechanism where phosphorylation is coupled to alternative DNA binding ways and which highlights the conformational dynamism of RcsB to be so pleiotropic.

    更新日期:2017-11-23
  • Dynamic m6A modification regulates local translation of mRNA in axons
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Jun Yu, Mengxian Chen, Haijiao Huang, Junda Zhu, Huixue Song, Jian Zhu, Jaewon Park, Sheng-Jian Ji

    N6-methyladenosine (m6A) is a reversible modification in mRNA and has been shown to regulate processing, translation and decay of mRNA. However, the roles of m6A modification in neuronal development are still not known. Here, we found that the m6A eraser FTO is enriched in axons and can be locally translated. Axon-specific inhibition of FTO by rhein, or compartmentalized siRNA knockdown of Fto in axons led to increases of m6A levels. GAP-43 mRNA is modified by m6A and is a substrate of FTO in axons. Loss-of-function of this non-nuclear pool of FTO resulted in increased m6A modification and decreased local translation of axonal GAP-43 mRNA, which eventually repressed axon elongation. Mutation of a predicted m6A site in GAP-43 mRNA eliminated its m6A modification and exempted regulation of its local translation by axonal FTO. This work showed an example of dynamic internal m6A demethylation of non-nuclear localized mRNA by the demethylase FTO. Regulation of m6A modification of axonal mRNA by axonal FTO might be a general mechanism to control their local translation in neuronal development.

    更新日期:2017-11-23
  • Biochemical and structural characterization of a novel cooperative binding mode by Pit-1 with CATT repeats in the macrophage migration inhibitory factor promoter
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Sorabh Agarwal, Thomas Yoonsang Cho

    Overexpression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) is linked to a number of autoimmune diseases and cancer. MIF production has been correlated to the number of CATT repeats in a microsatellite region upstream of the MIF gene. We have characterized the interaction of pituitary-specific positive transcription factor 1 (Pit-1) with a portion of the MIF promoter region flanking a microsatellite polymorphism (−794 CATT5–8). Using fluorescence anisotropy, we quantified tight complex formation between Pit-1 and an oligonucleotide consisting of eight consecutive CATT repeats (8xCATT) with an apparent Kd of 35 nM. Using competition experiments we found a 23 base pair oligonucleotide with 4xCATT repeats to be the minimum DNA sequence necessary for high affinity interaction with Pit-1. The stoichiometry of the Pit-1 DNA interaction was determined to be 2:1 and binding is cooperative in nature. We subsequently structurally characterized the complex and discovered a completely novel binding mode for Pit-1 in contrast to previously described Pit-1 complex structures. The affinity of Pit-1 for the CATT target sequence was found to be highly dependent on cooperativity. This work lays the groundwork for understanding transcriptional regulation of MIF and pursuing Pit-1 as a therapeutic target to treat MIF-mediated inflammatory disorders.

    更新日期:2017-11-23
  • Inhibition of DNA replication by an anti-PCNA aptamer/PCNA complex
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Ewa Kowalska, Filip Bartnicki, Ryo Fujisawa, Piotr Bonarek, Paweł Hermanowicz, Toshiki Tsurimoto, Klaudia Muszyńska, Wojciech Strzalka

    Proliferating cell nuclear antigen (PCNA) is a multifunctional protein present in the nuclei of eukaryotic cells that plays an important role as a component of the DNA replication machinery, as well as DNA repair systems. PCNA was recently proposed as a potential non-oncogenic target for anti-cancer therapy. In this study, using the Systematic Evolution of Ligands by EXponential enrichment (SELEX) method, we developed a short DNA aptamer that binds human PCNA. In the presence of PCNA, the anti-PCNA aptamer inhibited the activity of human DNA polymerase δ and ϵ at nM concentrations. Moreover, PCNA protected the anti-PCNA aptamer against the exonucleolytic activity of these DNA polymerases. Investigation of the mechanism of anti-PCNA aptamer-dependent inhibition of DNA replication revealed that the aptamer did not block formation, but was a component of PCNA/DNA polymerase δ or ϵ complexes. Additionally, the anti-PCNA aptamer competed with the primer-template DNA for binding to the PCNA/DNA polymerase δ or ϵ complex. Based on the observations, a model of anti-PCNA aptamer/PCNA complex-dependent inhibition of DNA replication was proposed.

    更新日期:2017-11-23
  • DNA as UV light–harvesting antenna
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Ivan L. Volkov, Zakhar V. Reveguk, Pavel Yu. Serdobintsev, Ruslan R. Ramazanov, Alexei I. Kononov

    The ordered structure of UV chromophores in DNA resembles photosynthetic light-harvesting complexes in which quantum coherence effects play a major role in highly efficient directional energy transfer. The possible role of coherent excitons in energy transport in DNA remains debated. Meanwhile, energy transport properties are greatly important for understanding the mechanisms of photochemical reactions in cellular DNA and for DNA-based artificial nanostructures. Here, we studied energy transfer in DNA complexes formed with silver nanoclusters and with intercalating dye (acridine orange). Steady-state fluorescence measurements with two DNA templates (15-mer DNA duplex and calf thymus DNA) showed that excitation energy can be transferred to the clusters from 21 and 28 nucleobases, respectively. This differed from the DNA–acridine orange complex for which energy transfer took place from four neighboring bases only. Fluorescence up-conversion measurements showed that the energy transfer took place within 100 fs. The efficient energy transport in the Ag–DNA complexes suggests an excitonic mechanism for the transfer, such that the excitation is delocalized over at least four and seven stacked bases, respectively, in one strand of the duplexes stabilizing the clusters. This result demonstrates that the exciton delocalization length in some DNA structures may not be limited to just two bases.

    更新日期:2017-11-23
  • JUNB governs a feed-forward network of TGFβ signaling that aggravates breast cancer invasion
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Anders Sundqvist, Masato Morikawa, Jiang Ren, Eleftheria Vasilaki, Natsumi Kawasaki, Mai Kobayashi, Daizo Koinuma, Hiroyuki Aburatani, Kohei Miyazono, Carl-Henrik Heldin, Hans van Dam, Peter ten Dijke

    It is well established that transforming growth factor-β (TGFβ) switches its function from being a tumor suppressor to a tumor promoter during the course of tumorigenesis, which involves both cell-intrinsic and environment-mediated mechanisms. We are interested in breast cancer cells, in which SMAD mutations are rare and interactions between SMAD and other transcription factors define pro-oncogenic events. Here, we have performed chromatin immunoprecipitation (ChIP)-sequencing analyses which indicate that the genome-wide landscape of SMAD2/3 binding is altered after prolonged TGFβ stimulation. De novo motif analyses of the SMAD2/3 binding regions predict enrichment of binding motifs for activator protein (AP)1 in addition to SMAD motifs. TGFβ-induced expression of the AP1 component JUNB was required for expression of many late invasion-mediating genes, creating a feed-forward regulatory network. Moreover, we found that several components in the WNT pathway were enriched among the late TGFβ-target genes, including the invasion-inducing WNT7 proteins. Consistently, overexpression of WNT7A or WNT7B enhanced and potentiated TGFβ-induced breast cancer cell invasion, while inhibition of the WNT pathway reduced this process. Our study thereby helps to explain how accumulation of pro-oncogenic stimuli switches and stabilizes TGFβ-induced cellular phenotypes of epithelial cells.

    更新日期:2017-11-23
  • Permissive zones for the centromere-binding protein ParB on the Caulobacter crescentus chromosome
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    Ngat T. Tran, Clare E. Stevenson, Nicolle F. Som, Anyarat Thanapipatsiri, Adam S. B. Jalal, Tung B. K. Le

    Proper chromosome segregation is essential in all living organisms. In Caulobacter crescentus, the ParA–ParB–parS system is required for proper chromosome segregation and cell viability. The bacterial centromere-like parS DNA locus is the first to be segregated following chromosome replication. parS is bound by ParB protein, which in turn interacts with ParA to partition the ParB-parS nucleoprotein complex to each daughter cell. Here, we investigated the genome-wide distribution of ParB on the Caulobacter chromosome using a combination of in vivo chromatin immunoprecipitation (ChIP-seq) and in vitro DNA affinity purification with deep sequencing (IDAP-seq). We confirmed two previously identified parS sites and discovered at least three more sites that cluster ∼8 kb from the origin of replication. We showed that Caulobacter ParB nucleates at parS sites and associates non-specifically with ∼10 kb flanking DNA to form a high-order nucleoprotein complex on the left chromosomal arm. Lastly, using transposon mutagenesis coupled with deep sequencing (Tn-seq), we identified a ∼500 kb region surrounding the native parS cluster that is tolerable to the insertion of a second parS cluster without severely affecting cell viability. Our results demonstrate that the genomic distribution of parS sites is highly restricted and is crucial for chromosome segregation in Caulobacter.

    更新日期:2017-11-23
  • Robust detection of chromosomal interactions from small numbers of cells using low-input Capture-C
    Nucleic Acids Res. (IF 10.162) Pub Date : 2017-11-23
    A. Marieke Oudelaar, James O.J. Davies, Damien J. Downes, Douglas R. Higgs, Jim R. Hughes

    Chromosome conformation capture (3C) techniques are crucial to understanding tissue-specific regulation of gene expression, but current methods generally require large numbers of cells. This hampers the investigation of chromatin architecture in rare cell populations. We present a new low-input Capture-C approach that can generate high-quality 3C interaction profiles from 10 000–20 000 cells, depending on the resolution used for analysis. We also present a PCR-free, sequencing-free 3C technique based on NanoString technology called C-String. By comparing C-String and Capture-C interaction profiles we show that the latter are not skewed by PCR amplification. Furthermore, we demonstrate that chromatin interactions detected by Capture-C do not depend on the degree of cross-linking by performing experiments with varying formaldehyde concentrations.

    更新日期:2017-11-23
  • 更新日期:2017-11-23
  • Synthesis and in Vitro Evaluation of Monodisperse Amino-Functional Polyester Dendrimers with Rapid Degradability and Antibacterial Properties
    Biomacromolecules (IF 5.246) Pub Date : 2017-11-22
    Patrik Stenström, Erik Hjorth, Yuning Zhang, Oliver C. J. Andrén, Simon Guette-Marquet, Marianne Schultzberg, Michael Malkoch
    更新日期:2017-11-23
  • Evaluating in Vitro Culture Medium of Gut Microbiome with Orthogonal Experimental Design and a Metaproteomics Approach
    J. Proteome Res. (IF 4.268) Pub Date : 2017-11-22
    Leyuan Li, Xu Zhang, Zhibin Ning, Janice Mayne, Jasmine I. Moore, James Butcher, Cheng-Kang Chiang, David Mack, Alain Stintzi, Daniel Figeys
    更新日期:2017-11-23
  • 更新日期:2017-11-23
  • Comparative proteomic analysis of lysine acetylation in Trypanosomes
    J. Proteome Res. (IF 4.268) Pub Date : 2017-11-23
    Nilmar Silvio Moretti, Igor Cestari, Atashi Anupama, Ken Stuart, Sergio Schenkman

    Protein acetylation is a post-translational modification regulating diverse cellular processes. By using proteomic approaches we identified N-terminal and ε-lysine acetylated proteins in Trypanosoma cruzi and Trypanosoma brucei, which are protozoan parasites that cause significant human and animal diseases. We detected 288 lysine acetylation sites in 210 proteins of procyclic form, an insect stage of T. brucei, and 380 acetylation sites in 285 proteins in the form of the parasite that replicates in mammalian bloodstream. In T. cruzi insect proliferative form we found 389 ε-lysine-acetylated sites in 235 proteins. Notably, we found distinct acetylation profiles according to the developmental stage and species, with only 44 common proteins between T. brucei stages and 18 in common between the two species. While K-ac proteins from T. cruzi are enriched in enzymes involved in oxidation/reduction balance, required for the parasite survival in the host, in T. brucei, most K-ac proteins are enriched in metabolic processes, essential for its adaptation in its hosts. We also identified in both parasites a quite variable N-terminal acetylation sites. Our results suggest that protein acetylation is involved in differential regulation of multiple cellular processes in Trypanosomes, contributing to our understanding of the essential mechanisms for parasite infection and survival.

    更新日期:2017-11-23
  • Deoxycholate-Enhanced Shigella Virulence Is Regulated by a Rare π-Helix in the Type Three Secretion System Tip Protein IpaD
    Biochemistry (IF 2.938) Pub Date : 2017-11-22
    Abram R. Bernard, T. Carson Jessop, Prashant Kumar, Nicholas E. Dickenson
    更新日期:2017-11-23
  • Deconstructing Lipid Kinase Inhibitors by Chemical Proteomics
    Biochemistry (IF 2.938) Pub Date : 2017-11-22
    Rebecca L. McCloud, Caroline E. Franks, Sean T. Campbell, Benjamin W. Purow, Thurl E. Harris, Ku-Lung Hsu
    更新日期:2017-11-23
  • The mechanism of variability in transcription start site selection
    eLife (IF 7.725) Pub Date : 2017-11-23
    Libing Yu, Jared Winkelman, Chirangini Pukhrambam, Terence Strick, Bryce E Nickels, Richard H Ebright

    During transcription initiation, RNA polymerase (RNAP) binds to promoter DNA, unwinds promoter DNA to form an RNAP-promoter open complex (RPo) containing a single-stranded 'transcription bubble,' and selects a transcription start site (TSS). TSS selection occurs at different positions within the promoter region, depending on promoter sequence and initiating-substrate concentration. Variability in TSS selection has been proposed to involve DNA 'scrunching' and 'anti-scrunching,' the hallmarks of which are: (i) forward and reverse movement of the RNAP leading edge, but not trailing edge, relative to DNA, and (ii) expansion and contraction of the transcription bubble. Here, using in vitro and in vivo protein-DNA photocrosslinking and single-molecule nanomanipulation, we show bacterial TSS selection exhibits both hallmarks of scrunching and anti-scrunching, and we define energetics of scrunching and anti-scrunching. The results establish the mechanism of TSS selection by bacterial RNAP and suggest a general mechanism for TSS selection by bacterial, archaeal, and eukaryotic RNAP.

    更新日期:2017-11-23
  • Jak2-mediated phosphorylation of Atoh1 is critical for medulloblastoma growth
    eLife (IF 7.725) Pub Date : 2017-11-23
    Tiemo J Klisch, Anna Vainshtein, Akash J Patel, Huda Y Zoghbi

    Treatment for medulloblastoma, the most common malignant brain tumor in children, remains limited to surgical resection, radiation, and traditional chemotherapy; with long-term survival as low as 50-60% for Sonic Hedgehog (Shh)-type medulloblastoma. We have shown that the transcription factor Atonal homologue 1 (Atoh1) is required for Shh-type medulloblastoma development in mice. To determine whether reducing either Atoh1 levels or activity in the tumor after its development, we studied Atoh1 dosage and modifications in Shh-type medulloblastoma. Heterozygosity of Atoh1 reduced tumor occurrence and prolonged survival. We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human SHH-type medulloblastoma. Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1's transcriptional activity, and is independent of canonical Jak2 signaling. Importantly, inhibition of Jak2 impairs tyrosine 78 phosphorylation and tumor growth in vivo. Taken together, inhibiting Jak2-mediated tyrosine 78 phosphorylation could provide a viable therapy for medulloblastoma.

    更新日期:2017-11-23
  • The mechanism of variability in transcription start site selection
    eLife (IF 7.725) Pub Date : 2017-11-23
    Libing Yu, Jared Winkelman, Chirangini Pukhrambam, Terence Strick, Bryce E Nickels, Richard H Ebright

    During transcription initiation, RNA polymerase (RNAP) binds to promoter DNA, unwinds promoter DNA to form an RNAP-promoter open complex (RPo) containing a single-stranded 'transcription bubble,' and selects a transcription start site (TSS). TSS selection occurs at different positions within the promoter region, depending on promoter sequence and initiating-substrate concentration. Variability in TSS selection has been proposed to involve DNA 'scrunching' and 'anti-scrunching,' the hallmarks of which are: (i) forward and reverse movement of the RNAP leading edge, but not trailing edge, relative to DNA, and (ii) expansion and contraction of the transcription bubble. Here, using in vitro and in vivo protein-DNA photocrosslinking and single-molecule nanomanipulation, we show bacterial TSS selection exhibits both hallmarks of scrunching and anti-scrunching, and we define energetics of scrunching and anti-scrunching. The results establish the mechanism of TSS selection by bacterial RNAP and suggest a general mechanism for TSS selection by bacterial, archaeal, and eukaryotic RNAP.

    更新日期:2017-11-23
  • Jak2-mediated phosphorylation of Atoh1 is critical for medulloblastoma growth
    eLife (IF 7.725) Pub Date : 2017-11-23
    Tiemo J Klisch, Anna Vainshtein, Akash J Patel, Huda Y Zoghbi

    Treatment for medulloblastoma, the most common malignant brain tumor in children, remains limited to surgical resection, radiation, and traditional chemotherapy; with long-term survival as low as 50-60% for Sonic Hedgehog (Shh)-type medulloblastoma. We have shown that the transcription factor Atonal homologue 1 (Atoh1) is required for Shh-type medulloblastoma development in mice. To determine whether reducing either Atoh1 levels or activity in the tumor after its development, we studied Atoh1 dosage and modifications in Shh-type medulloblastoma. Heterozygosity of Atoh1 reduced tumor occurrence and prolonged survival. We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human SHH-type medulloblastoma. Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1's transcriptional activity, and is independent of canonical Jak2 signaling. Importantly, inhibition of Jak2 impairs tyrosine 78 phosphorylation and tumor growth in vivo. Taken together, inhibiting Jak2-mediated tyrosine 78 phosphorylation could provide a viable therapy for medulloblastoma.

    更新日期:2017-11-23
  • Hypothalamic-pituitary-testicular axis and testicular function are modulated after silver nanoparticles exposure
    Toxicol. Res. (IF 1.969) Pub Date : 2017-11-23
    Monica D Cavallin, Rebeca Wilk, Isabela Medeiros de Oliveira, Nathalia C S Cardoso, Najeh Maissar Khalil, Claudio Alvarenga de Oliveira, Marco Aurelio Romano, Renata Marino Romano

    Silver nanoparticles (AgNPs) are widely used in industrial and medical applications and humans may be exposed through different routes, increasing the risk of toxicity. We investigated the transcript expression of genes involved in the regulation of the hypothalamic-pituitary-testicular (HPT) axis and the parameters associated with sperm functionality after prepubertal exposure. AgNPs modulated the transcript expression of genes involved in the control of the HPT axis and spermatogenesis in the groups treated with lower doses, while the functional parameters related to sperm and puberty were affected in the groups administered higher doses. These results suggest that the HPT axis is disrupted by AgNPs during the prepubertal and pubertal periods, which are highly susceptible windows for the endocrine-disrupting chemical activity.

    更新日期:2017-11-23
  • IN VITRO EFFECTS OF ENDOSULFAN-BASED INSECTICIDES ON MAMMALIAN SPERM
    Toxicol. Res. (IF 1.969) Pub Date : 2017-11-23
    Melisa Celeste Sanchez, Cristian Alvarez Sedo, Gabriela Chaufan, Marina Romanato, Rodrigo Da Cuña, Fabiana Lo Nostro, Juan Carlos Calvo, Vanina Andrea Fontana

    Endosulfan is an organochloride insecticide extensively used in several countries to protect crops from pests. As several studies indicate that endosulfan can affect human and animal development, the aim of this study is to analyse if sperm parameters and the process of chromatin decondensation could be altered in mice sperm. Spermatozoa from cauda epididymis were obtained from mature male mice and incubated in the presence of two commercial formulations (CF) of endosulfan (Master® and Zebra Ciagro®) and the active ingredient (AI) alone. A significant decrease in percentage motility and viability of spermatozoa with respect to controls was found. In vitro decondensation was performed in the presence of glutathione and heparin. Spermatozoa incubated with AI, endosulfan Master® and endosulfan Zebra Ciagro® showed an increase in chromatin decondensation. In addition, TUNEL assay showed that DNA fragmentation was significantly higher when sperm were incubated with either one of the CF when compared to AI or controls. Ultrastructure analysis of sperm cells showed evident changes in the structure of the plasma and acrosome membranes of the sperm incubated with endosulfan AI or the CFs. These results suggest that endosulfan can affect sperm integrity and in vitro chromatin decondensation as well as DNA fragmentation.

    更新日期:2017-11-23
  • 更新日期:2017-11-23
  • High-Affinity Nucleic-Acid-Based Receptors for Steroids
    ACS Chem. Biol. (IF 4.995) Pub Date : 2017-11-22
    Kyung-Ae Yang, Hyosun Chun, Yameng Zhang, Stevan Pecic, Nako Nakatsuka, Anne M. Andrews, Tilla S. Worgall, Milan N. Stojanovic
    更新日期:2017-11-23
  • Diisonitrile Natural Product SF2768 Functions As a Chalkophore That Mediates Copper Acquisition in Streptomyces thioluteus
    ACS Chem. Biol. (IF 4.995) Pub Date : 2017-11-22
    Lijuan Wang, Mengyi Zhu, Qingbo Zhang, Xu Zhang, Panlei Yang, Zihui Liu, Yun Deng, Yiguang Zhu, Xueshi Huang, Li Han, Shengqing Li, Jing He
    更新日期:2017-11-23
  • Organoselenium compounds as mimics of selenoproteins and thiol modifier agents
    Metallomics (IF 3.975) Pub Date : 2017-11-23
    Nilda V. Barbosa, Cristina W. Nogueira, Pablo A. Nogara, Andreza F. de Bem, Michael Aschner, João B. T. Rocha
    更新日期:2017-11-23
  • Bioreactor model of neuromuscular junction with electrical stimulation for pharmacological potency testing
    Integr. Biol. (IF 3.252) Pub Date : 2017-11-14
    Surapon N. Charoensook, Damian J. Williams, Syandan Chakraborty, Kam W. Leong, Gordana Vunjak-Novakovic
    更新日期:2017-11-23
  • Probing impaired neurogenesis in human brain organoids exposed to alcohol
    Integr. Biol. (IF 3.252) Pub Date : 2017-11-09
    Yujuan Zhu, Li Wang, Fangchao Yin, Yue Yu, Yaqing Wang, Matthew J. Shepard, Zhengping Zhuang, Jianhua Qin
    更新日期:2017-11-23
  • Movers and Stayers: Novel Assemblages in Changing Environments
    Trends Ecol. Evol. (IF 15.268) Pub Date : 2017-11-21
    Richard J. Hobbs, Leonie E. Valentine, Rachel J. Standish, Stephen T. Jackson

    Increased attention to species movement in response to environmental change highlights the need to consider changes in species distributions and altered biological assemblages. Such changes are well known from paleoecological studies, but have accelerated with ongoing pervasive human influence. In addition to species that move, some species will stay put, leading to an array of novel interactions. Species show a variety of responses that can allow movement or persistence. Conservation and restoration actions have traditionally focused on maintaining or returning species in particular places, but increasingly also include interventions that facilitate movement. Approaches are required that incorporate the fluidity of biotic assemblages into the goals set and interventions deployed.

    更新日期:2017-11-22
  • Zebrafish Infection: From Pathogenesis to Cell Biology
    Trends Cell Biol. (IF 15.333) Pub Date : 2017-11-21
    Vincenzo Torraca, Serge Mostowy

    The study of host–pathogen interactions has illuminated fundamental research avenues in both infection and cell biology. Zebrafish (Danio rerio) larvae are genetically tractable, optically accessible, and present a fully functional innate immune system with macrophages and neutrophils that mimic their mammalian counterparts. A wide variety of pathogenic bacteria have been investigated using zebrafish models, providing unprecedented resolution of the cellular response to infection in vivo. In this review, we illustrate how zebrafish models have contributed to our understanding of cellular microbiology by providing an in vivo platform to study host–pathogen interactions from the single cell to whole animal level. We also highlight discoveries made from zebrafish infection that hold great promise for translation into novel therapies for humans.

    更新日期:2017-11-22
  • Microtubule-Organizing Centers: Towards a Minimal Parts List
    Trends Cell Biol. (IF 15.333) Pub Date : 2017-11-21
    Joel Paz, Jens Lüders

    Despite decades of molecular analysis of the centrosome, an important microtubule-organizing center (MTOC) of animal cells, the molecular basis of microtubule organization remains obscure. A major challenge is the sheer complexity of the interplay of the hundreds of proteins that constitute the centrosome. However, this complexity owes not only to the centrosome’s role as a MTOC but also to the requirements of its duplication cycle and to various other functions such as the formation of cilia, the integration of various signaling pathways, and the organization of actin filaments. Thus, rather than using the parts lists to reconstruct the centrosome, we propose to identify the subset of proteins minimally needed to assemble a MTOC and to study this process at non-centrosomal sites.

    更新日期:2017-11-22
  • 更新日期:2017-11-22
  • 更新日期:2017-11-22
  • Swell, or Not Too Swell: Cytokines Regulate Arterial Aneurysm Formation
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Peter Libby, Amélie Vrooman
    更新日期:2017-11-22
  • A Sweet Solution: Glycolysis-Dependent Treg Cell Migration
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Ronen Alon
    更新日期:2017-11-22
  • TGF-β Gives an Air of Exclusivity to Alveolar Macrophages
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Bart N. Lambrecht
    更新日期:2017-11-22
  • The Skinny: Pancreatic ILC2s Promote Insulin Secretion
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Kelly M. Cautivo, Ari B. Molofsky
    更新日期:2017-11-22
  • HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Elise Landais, Ben Murrell, Bryan Briney, Sasha Murrell, Kimmo Rantalainen, Zachary T. Berndsen, Alejandra Ramos, Lalinda Wickramasinghe, Melissa Laird Smith, Kemal Eren, Natalia de Val, Mengyu Wu, Audrey Cappelletti, Jeffrey Umotoy, Yolanda Lie, Terri Wrin, Paul Algate, Po-Ying Chan-Hui, Etienne Karita, Andrew B. Ward, Ian A. Wilson, Dennis R. Burton, Davey Smith, Sergei L. Kosakovsky Pond, Pascal Poignard
    更新日期:2017-11-22
  • Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Alberto Yáñez, Simon G. Coetzee, Andre Olsson, David E. Muench, Benjamin P. Berman, Dennis J. Hazelett, Nathan Salomonis, H. Leighton Grimes, Helen S. Goodridge
    更新日期:2017-11-22
  • Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Caren E. Petrie Aronin, Yun M. Zhao, Justine S. Yoon, Nicole Y. Morgan, Thorsten Prüstel, Ronald N. Germain, Martin Meier-Schellersheim
    更新日期:2017-11-22
  • Brain, Immunity, Gut: “BIG” Links between Pregnancy and Autism
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Myka L. Estes, A. Kimberley McAllister
    更新日期:2017-11-22
  • The TCR Takes Some Immune Responsibility
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Ashley A. Viehmann Milam, Paul M. Allen
    更新日期:2017-11-22
  • Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Madhav Kishore, Kenneth C.P. Cheung, Hongmei Fu, Fabrizia Bonacina, Guosu Wang, David Coe, Eleanor J. Ward, Alessandra Colamatteo, Maryam Jangani, Andrea Baragetti, Giuseppe Matarese, David M. Smith, Robert Haas, Claudio Mauro, David C. Wraith, Klaus Okkenhaug, Alberico L. Catapano, Veronica De Rosa, Giuseppe D. Norata, Federica M. Marelli-Berg
    更新日期:2017-11-22
  • Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Elise Dalmas, Frank M. Lehmann, Erez Dror, Stephan Wueest, Constanze Thienel, Marcela Borsigova, Marc Stawiski, Emmanuel Traunecker, Fabrizio C. Lucchini, Dianne H. Dapito, Sandra M. Kallert, Bruno Guigas, Francois Pattou, Julie Kerr-Conte, Pierre Maechler, Jean-Philippe Girard, Daniel Konrad, Christian Wolfrum, Marianne Böni-Schnetzler, Daniela Finke, Marc Y. Donath
    更新日期:2017-11-22
  • Glycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Raiees Andrabi, Ching-Yao Su, Chi-Hui Liang, Sachin S. Shivatare, Bryan Briney, James E. Voss, Salar Khan Nawazi, Chung-Yi Wu, Chi-Huey Wong, Dennis R. Burton

    (Immunity 47, 524–537; September 19, 2017)

    更新日期:2017-11-22
  • A CD103+ Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis
    Immunity (IF 22.845) Pub Date : 2017-11-21
    Xavier Clemente-Casares, Siyavash Hosseinzadeh, Iulia Barbu, Sarah A. Dick, Jillian A. Macklin, Yiming Wang, Abdul Momen, Crystal Kantores, Laura Aronoff, Maylis Farno, Tiffany M. Lucas, Joan Avery, Dorrin Zarrin-Khat, Heidi J. Elsaesser, Babak Razani, Kory J. Lavine, Mansoor Husain, David G. Brooks, Clinton S. Robbins, Myron Cybulsky, Slava Epelman
    更新日期:2017-11-22
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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