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| Open AccessThe IncP-1 plasmid backbone adapts to different host bacterial species and evolves through homologous recombination
Plasmids are present in many bacteria and are often transferred between different species causing horizontal gene transfer. By comparing the sequences of 25 plasmid DNA backbones, the authors show that homologous recombination is prevalent in plasmids and that the plasmids have adapted to persist in different host bacteria.
- Peter Norberg
- , Maria Bergström
- & Malte Hermansson
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The acetylation of tau inhibits its function and promotes pathological tau aggregation
Phosphorylation of the microtubule-associated protein tau is associated with disease, but other post-translational modifications of tau are not well studied. Here, Cohenet al. study the acetylation of tau and suggest that this form of the protein may be associated with tauopathies.
- Todd J. Cohen
- , Jing L. Guo
- & Virginia M. Y. Lee
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Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25
Sox9 is an important transcription factor in the formation of cartilage chondrogenesis that occurs during skeletal development. Nakamuraet al.show that Sox9 interacts with Wwp2 and Med25 to form a complex and that loss of either protein in zebrafish results in altered palate chondrogenesis.
- Yukio Nakamura
- , Koji Yamamoto
- & Haruhiko Akiyama
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5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming
Pronucleus DNA becomes demethylated during zygotic development. Here, the authors demonstrate that the reduction in 5-methylcytosine levels is accompanied by an increase in the presence of 5-hydroxymethylcytosine, and suggest that this has a role in developmental reprogramming.
- Mark Wossidlo
- , Toshinobu Nakamura
- & Jörn Walter
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Larger mitochondrial DNA than Y-chromosome differences between matrilocal and patrilocal groups from Sumatra
Matrilocal and patrilocal populations are predicted to have greater genetic diversity in mitochondrial DNA and the Y-chromosome, respectively. Here, no difference in the diversity of the Y-chromosome was found in two such groups, suggesting that local diversity was caused by male gene flow in expanding populations.
- Ellen Dröfn Gunnarsdóttir
- , Madhusudan R. Nandineni
- & Mark Stoneking
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Article
| Open AccessThe structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain
CXXC domain proteins bind to CpG DNA sequences and influence chromatin modification. Xuet al.report crystal structures of the CXXC protein CFP1, a component of the SETD1 histone H3K4 methyl transferase complex, and study the molecular mechanisms of DNA-binding specificity.
- Chao Xu
- , Chuanbing Bian
- & Jinrong Min
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Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17
Activation of the receptor tyrosine kinases FGFR2 and VEGFR2 results in ERK1/2 phosphorylation and cell migration. Here, the authors demonstrate that shedding of HB-EGF—a substrate of the metalloproteinase ADAM17—and activation of EGFR is required for FGFR2 and VEGFR2 mediated cell migration.
- Thorsten Maretzky
- , Astrid Evers
- & Carl P. Blobel
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Article
| Open AccessHistone acetylation controls the inactive X chromosome replication dynamics
How one copy of the X chromosome is silenced in replicating female somatic cells is poorly understood. Here, the authors demonstrate that the inactive X chromosome is replicated before constitutive heterochromatin and that histone hypoacetylation has a role in controlling replication of the inactive X chromosome.
- Corella S. Casas-Delucchi
- , Alessandro Brero
- & M. Cristina Cardoso
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Article
| Open AccessCSN-mediated deneddylation differentially modulates Ci155 proteolysis to promote Hedgehog signalling responses
Hedgehog signalling gradients are required for proper wing formation inDrosophila, and Hedgehog is known to regulate the cubitus interruptus transcription factor. Here, the authors show that the COP9 signalosome has a critical role in translating a Hedgehog gradient into a cubitus interruptus gradient.
- June-Tai Wu
- , Wei-Hsiang Lin
- & Cheng-Ting Chien
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| Open AccessChromatin remodelling complex dosage modulates transcription factor function in heart development
Inherited congenital heart defects are prevalent in the human population, but the molecular mechanisms are poorly understood. In this article, deficiency in the chromatin remodelling factor, Brg1, is shown to alter cardiac development in both mouse and zebrafish laboratory models.
- Jun K. Takeuchi
- , Xin Lou
- & Benoit G. Bruneau
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Article
| Open AccessThe Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice
Post-translational modifications are important in regulating protein function and turnover, and Ufm1 is part of a recently identified protein modification system. In this study, the authors show that Uba5, a component of the Ufm1 system, is important for regulating haematopoiesis and the differentiation of erythroid cells.
- Kanako Tatsumi
- , Harumi Yamamoto-Mukai
- & Masaaki Komatsu
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Rad23 escapes degradation because it lacks a proteasome initiation region
Rad23 accompanies ubiquitinated substrates to the proteasome for destruction but manages to avoid degradation. In this study, Fishbainet al.show that Rad23 escapes because it lacks an effective initiation region; therefore, the proteasome is unable to engage the protein and unfold it.
- Susan Fishbain
- , Sumit Prakash
- & Andreas Matouschek
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ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA
Uridines at the wobble position of transfer RNA anticodons are usually modified to allow efficient decoding of messenger RNA codons. In this study, ALKBH8 is shown to be a bifunctional transfer RNA modification enzyme required for the formation of a novel diastereomeric pair of modified wobble uridines.
- Erwin van den Born
- , Cathrine B. Vågbø
- & Pål Ø. Falnes
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| Open AccessSynthetic human cell fate regulation by protein-driven RNA switches
The control of cell fate and apoptosis is a continuing challenge in synthetic biology. In this study, systems are developed in which an intracellularly expressed genome-encoded protein simultaneously achieves up- and downregulation of two distinct apoptosis pathways.
- Hirohide Saito
- , Yoshihiko Fujita
- & Tan Inoue
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Article
| Open AccessHerpesviruses carrying a Brainbow cassette reveal replication and expression of limited numbers of incoming genomes
The replication of viral genomes in infected cells is required for successful infection. In this study, using Cre-conditional expression of multiple coloured fluorophores, the authors demonstrate that the number of viral genomes expressed and replicated in a cell is surprisingly limited.
- Oren Kobiler
- , Yaron Lipman
- & Lynn W. Enquist
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A role for TREX components in the release of spliced mRNA from nuclear speckle domains
The pre-mRNA splicing and TREX mRNA export machineries are found in nuclear speckle domains. Diaset al. microinject CMV-DNA constructs into cells and find that transcripts containing functional splice sites accumulate in nuclear speckles and that the TREX complex is required to release the mRNA once processed.
- Anusha P. Dias
- , Kobina Dufu
- & Robin Reed
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Article
| Open AccessFolding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone
Toll-like receptors are involved in pathogen recognition by the innate immune system and rely on the molecular chaperone, gp96, for correct folding. In this article, the chaperone activity of gp96 is shown to be dependent on an additional endoplasmic reticulum protein, CNPY3, for some Toll-like receptors.
- Bei Liu
- , Yi Yang
- & Zihai Li
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Ice as a protocellular medium for RNA replication
A crucial transition in the origin of life was the emergence of self-replicating RNA and its compartmentalization within protocellular structures. Here it is shown that the physicochemical properties of ice, a simple medium widespread on a temperate early earth, could have mediated this transition.
- James Attwater
- , Aniela Wochner
- & Philipp Holliger
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Article
| Open AccessRapid calcium-dependent activation of Aurora-A kinase
Aurora-A kinase localizes to centrosomes, is involved in the progression through mitosis and is overexpressed in certain cancers. Here, calcium is shown to induce Aurora-A auto-phosphorylation in a calmodulin-dependent manner, suggesting a novel role for Aurora-A in non-mitotic cells.
- Olga V. Plotnikova
- , Elena N. Pugacheva
- & Erica A. Golemis
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| Open AccessIdentification of Thymosin β4 as an effector of Hand1-mediated vascular development
The Hand1 transcription factor plays a central role in cardiovascular development. Here the authors demonstrate that Hand1 regulates thymosin β4 and that the delivery of synthetic thymosin β4 can rescue some of the vascular defects in Hand1 null mouse embryos.
- Nicola Smart
- , Karina N. Dubé
- & Paul R. Riley
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Pseudogene-mediated posttranscriptional silencing of HMGA1 can result in insulin resistance and type 2 diabetes
Pseudogenes are prevalent in the human genome; however, their biological function is relatively unknown. In this study, the high mobility group A1 (HMGA1) pseudogene is shown to destabilizeHMGA1 mRNA. These findings have implications for diabetes, as two patients are reported to express high levels of the HMGA1pseudogene.
- Eusebio Chiefari
- , Stefania Iiritano
- & Antonio Brunetti
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PI(3,5)P2 controls membrane trafficking by direct activation of mucolipin Ca2+ release channels in the endolysosome
Phosphoinositides activate intracellular ion channels to release Ca2+ from membrane-bound stores. This study demonstrates that Ca2+-permeable mucolipin TRP channels, TRPMLs, are activated by the phospholipid PI(3,5)P2in murine endolysosomes and yeast vacuoles.
- Xian-ping Dong
- , Dongbiao Shen
- & Haoxing Xu
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TERRA transcripts are bound by a complex array of RNA-binding proteins
Recent work has revealed that the TTAGGG DNA repeats of telomeres are transcribed to form 'TERRA'. In this study, a set of RNA-binding proteins are shown to bind TERRA transcripts, altering the location of these transcripts at telomeres and regulating telomere abundance and length.
- Isabel López de Silanes
- , Martina Stagno d'Alcontres
- & Maria A Blasco
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Article
| Open AccessImaging the nanoscale organization of peptidoglycan in living Lactococcus lactis cells
Peptidoglycans provide bacterial cell walls with mechanical strength. The spatial organization of peptidoglycan has previously been difficult to study. Here, atomic force microscopy, together with cells carrying mutations in cell-wall polysaccharides, has allowed an in-depth study of these molecules.
- Guillaume Andre
- , Saulius Kulakauskas
- & Yves F. Dufrêne
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USE1 is a bispecific conjugating enzyme for ubiquitin and FAT10, which FAT10ylates itself in cis
The ubiquitin-like modifier FAT10 targets proteins for proteolytic degradation. Here the ubiquitin-conjugating enzyme USE1 is identified as a component of the FAT10 conjugation cascade.
- Annette Aichem
- , Christiane Pelzer
- & Marcus Groettrup
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Article
| Open AccessOrganogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors
During development Sox transcription factors play important roles in the determination of cell fate. In this study Bhattaram and colleagues show that Sox4, Sox11 and Sox12 act redundantly in mouse development and are important for the maintenance of neural and mesenchymal progenitor cells.
- Pallavi Bhattaram
- , Alfredo Penzo-Méndez
- & Véronique Lefebvre
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Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
Ageing associated diseases are the subject of intense study. In this article Serrano and colleagues demonstrate that Sirt1 over-expression in mice prevents both ageing associated diseases and liver cancer.
- Daniel Herranz
- , Maribel Muñoz-Martin
- & Manuel Serrano
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Mitochondrial respiration protects against oxygen-associated DNA damage
Oxygen is necessary for mitochondrial respiration; however it can also result in the formation of toxic reactive species that can cause DNA damage. Using cells defective in respiration these authors demonstrate that mitochondria protect a cell from these harmful effects of oxygen.
- Ho Joong Sung
- , Wenzhe Ma
- & Paul M. Hwang
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