April 2014

Cover articles

Highlights controls:

Research articles

    1. Neuroscience

    Monosynaptic premotor circuit tracing reveals neural substrates for oro-motor coordination

    Edward Stanek IV, Steven Cheng ... Fan Wang
    Retrograde tracing of the neural circuits that control movement of the jaw and tongue reveals how shared premotor neurons help to ensure coordinated muscle activity.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation

    Marta Carroni, Eva Kummer ... Helen R Saibil
    Overcoming image-processing problems in the analysis of the ClpB chaperone provides a new structural model and regulatory mechanism, based on clear density for the coiled-coil domain and supported by various biochemical data.
    1. Chromosomes and Gene Expression

    MicroRNAs down-regulate homologous recombination in the G1 phase of cycling cells to maintain genomic stability

    Young Eun Choi, Yunfeng Pan ... Dipanjan Chowdhury
    MicroRNAs tightly control the cellular level of homologous recombination (HR) factors in the G1 phase, and failure of this control system results in an ectopic increase in HR proteins in G1 cells leading to impaired DNA repair.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Cell-cycle dependent phosphorylation of yeast pericentrin regulates γ-TuSC-mediated microtubule nucleation

    Tien-chen Lin, Annett Neuner ... Elmar Schiebel
    Phosphorylation of Spc110 N-terminal domain encompassing conserved motifs and its interaction with conserved GCP3 N-terminal domain regulate the oligomerization of gamma-tubulin small complexes (γ-TuSCs).
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Transcription inhibition by the depsipeptide antibiotic salinamide A

    David Degen, Yu Feng ... Richard H Ebright
    Salinamide A exerts antibacterial activity by binding to the bridge-helix cap of bacterial RNA polymerase and allosterically inhibiting nucleotide addition
    1. Chromosomes and Gene Expression

    Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

    Daan Noordermeer, Marion Leleu ... Denis Duboule
    Hox genes are activated sequentially and, at the same time, undergo a transition from an inactive to an active chromatin compartment, most likely to prevent posterior genes being activated too early.
    1. Plant Biology

    Combining growth-promoting genes leads to positive epistasis in Arabidopsis thaliana

    Hannes Vanhaeren, Nathalie Gonzalez ... Dirk Inzé
    Pairwise combinations of growth-promoting genes regulating distinct cellular mechanisms lead to synergistic effects on leaf growth, and hence greatly increased leaf size.
    1. Biochemistry and Chemical Biology

    Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation

    Andrei S Avanesov, Siming Ma ... Vadim N Gladyshev
    Aging is a process characterized by gradual metabolome remodeling, deceleration of the remodeling in late life and under conditions that extend lifespan, and a mortality-associated pattern of cumulative damage.
    1. Structural Biology and Molecular Biophysics

    Periodic DNA patrolling underlies diverse functions of Pif1 on R-loops and G-rich DNA

    Ruobo Zhou, Jichuan Zhang ... Taekjip Ha
    Analyzing single molecules reveals that Pif1 family helicases periodically patrol DNA, which may explain this enzyme's ability to suppress genome instability at G-quadruplex motifs and transcriptional RNA-DNA hybrids (R-loops).
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Symmetry breaking in reconstituted actin cortices

    Enas Abu Shah, Kinneret Keren
    A reconstituted system has been developed that self-organizes into dynamic actin cortices capable of spontaneous polarization, similar to the initial cortical polarization observed in cells during embryogenesis and development.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Repair of naturally occurring mismatches can induce mutations in flanking DNA

    Jia Chen, Brendan F Miller, Anthony V Furano
    The repair of spontaneous DNA damage can introduce mutators that lead to further genetic changes, which could underlie evolutionary change, disease and aging.
    1. Cell Biology
    2. Ecology

    Systems analysis of the CO2 concentrating mechanism in cyanobacteria

    Niall M Mangan, Michael P Brenner
    Systems level modeling of cyanobacterial mechanism for concentrating carbon dioxide shows optimal organization and enzymatic activity for enhanced carbon fixation.
    1. Chromosomes and Gene Expression

    p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-κB complexes

    Michal Krawczyk, Beverly M Emerson
    A long non-coding RNA removes the transcriptional repressor p50 to regulate recruitment of co-activator p300 and RNA Polymerase II complexes to activate the COX-2 gene in human mammary epithelial cells and macrophages.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons

    Iris Jonkers, Hojoong Kwak, John T Lis
    The elongation rate of RNA Polymerase II varies greatly between and along genes, as this enzyme accelerates from stable pausing to rapid elongation within genes, and is influenced by CG-content, exons and chromatin.
    1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease

    Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1

    Xiaofei Jia, Erin Weber ... Yong Xiong
    HIV-1 viral protein u (Vpu) can stimulate novel versions of canonical interactions with the clathrin adaptor AP1 to counteract the host antiviral protein BST2.
    1. Structural Biology and Molecular Biophysics
    2. Chromosomes and Gene Expression

    Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network

    Jerome C Nwachukwu, Sathish Srinivasan ... Kendall W Nettles
    Anti-inflammatory effects of resveratrol are mediated by the estrogen receptor to coordinate a complex array of transcriptional coregulators, suggesting that estrogenic effects must be considered in the complex polypharmacology of resveratrol.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

    Ivana Petrovska, Elisabeth Nüske ... Simon Alberti
    A starvation-induced drop in cytosolic pH promotes assembly of budding yeast glutamine synthetase into enzymatically inactive filaments that function as enzyme storage depots.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Genetic interactions affecting human gene expression identified by variance association mapping

    Andrew Anand Brown, Alfonso Buil ... Richard Durbin
    Multiple replicated examples of epistasis affecting gene expression in humans are identified, some explaining a substantial proportion of the variation in expression.
    1. Plant Biology

    Brassinosteroids control root epidermal cell fate via direct regulation of a MYB-bHLH-WD40 complex by GSK3-like kinases

    Yinwei Cheng, Wenjiao Zhu ... Xuelu Wang
    Brassinosteroids signal through a pathway involving GSK3-like kinases and the WER-GL3/EGL3-TTG1 transcription factor complex to determine the fate of cells in the root epidermis.
    1. Developmental Biology

    Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors

    Lincoln T Shenje, Peter Andersen ... Chulan Kwon
    Cardiac progenitors remain undifferentiated and expansive in the second pharyngeal arch that serves as a microenvironment, and Numb and Numblike are required for their renewal.
    1. Chromosomes and Gene Expression

    Targeted genome editing by lentiviral protein transduction of zinc-finger and TAL-effector nucleases

    Yujia Cai, Rasmus O Bak, Jacob Giehm Mikkelsen
    Lentiviral protein transduction offers a new approach for administration of custom-designed nucleases, leading to high-efficacy targeted gene editing and reduced off-target activity after virus-directed delivery of programmable nuclease proteins.
    1. Structural Biology and Molecular Biophysics
    2. Chromosomes and Gene Expression

    AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter

    Ursula Schulze-Gahmen, Huasong Lu ... Tom Alber
    AFF4 increases the combined selectivity of HIV Tat and TAR for super elongation complexes 330-fold over P-TEFb alone.
    1. Genetics and Genomics

    APOBEC3A deaminates transiently exposed single-strand DNA during LINE-1 retrotransposition

    Sandra R Richardson, Iñigo Narvaiza ... John V Moran
    Combining in vitro and in vivo assays demonstrates that the cytidine deaminase APOBEC3A can inhibit LINE-1 retrotransposition by deaminating transiently exposed single-strand DNA that arises during the process of LINE-1 integration.
    1. Genetics and Genomics
    2. Plant Biology

    A gene horizontally transferred from bacteria protects arthropods from host plant cyanide poisoning

    Nicky Wybouw, Wannes Dermauw ... Thomas Van Leeuwen
    The enzyme that allows some mites and insects to detoxify the hydrogen cyanide produced by plants has been identified.
    1. Neuroscience

    Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis

    Nicolas X Tritsch, Won-Jong Oh ... Bernardo L Sabatini
    The molecular mechanisms by which midbrain dopamine neurons acquire the inhibitory neurotransmitter GABA for synaptic release are revealed.
    1. Cell Biology

    The GTPase IFT27 is involved in both anterograde and retrograde intraflagellar transport

    Diego Huet, Thierry Blisnick ... Philippe Bastin
    A small GTPase within the flagellum can participate in the control of transport from the base to the tip of the flagellum, and back again.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots

    Philip Bejon, Thomas N Williams ... Steffen Borrmann
    Malaria 'hotspots' can be identified that range in size from a few homesteads to a village, and it will be necessary to eliminate hotspots at varying scales as we progress towards eliminating malaria.
    1. Biochemistry and Chemical Biology

    DNA polymerase V activity is autoregulated by a novel intrinsic DNA-dependent ATPase

    Aysen L Erdem, Malgorzata Jaszczur ... Myron F Goodman
    DNA synthesis by DNA polymerase V is regulated by an intrinsic DNA-dependent ATPase activity which has not been observed for any other polymerase.
    1. Neuroscience

    SIR-2.1 integrates metabolic homeostasis with the reproductive neuromuscular excitability in early aging male Caenorhabditis elegans

    Xiaoyan Guo, L René García
    A protein called SIR-2.1 helps to protect worms from the effects of aging by regulating metabolic processes that would otherwise generate damaging reactive oxygen species.
    1. Stem Cells and Regenerative Medicine

    Transgressions of compartment boundaries and cell reprogramming during regeneration in Drosophila

    Salvador C Herrera, Ginés Morata
    The reconstruction of damaged structures during regeneration requires cell reprogramming mediated by the up regulation of the JNK pathway and the transient debilitation of the epigenetic control mechanism.
    1. Neuroscience

    Gating of neural error signals during motor learning

    Rhea R Kimpo, Jacob M Rinaldi ... Jennifer L Raymond
    Electrode recordings and optogenetics reveal that the cerebellum can modulate its response to error signals from the brainstem during motor learning.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    GE23077 binds to the RNA polymerase ‘i’ and ‘i+1’ sites and prevents the binding of initiating nucleotides

    Yu Zhang, David Degen ... Richard H Ebright
    The cyclic-peptide antibiotic GE23077 inhibits bacterial RNA polymerase through a novel target that exhibits low susceptibility to target-based resistance and that enables synthesis of bipartite inhibitors that are exceptionally potent and refractory to target-based resistance.
    1. Developmental Biology
    2. Chromosomes and Gene Expression

    Requirement for highly efficient pre-mRNA splicing during Drosophila early embryonic development

    Leonardo Gastón Guilgur, Pedro Prudêncio ... Rui Gonçalo Martinho
    The need for efficient pre-RNA splicing during early embryonic development of Drosophila indicates that the constraints imposed by the cell cycle are a force capable of driving changes in Eukaryotic gene architecture.
    1. Neuroscience

    RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling

    Olga Ostrovskaya, Keqiang Xie ... Kirill A Martemyanov
    A critical regulator of inhibitory neurotransmitter signaling in the hippocampus has been identified in experiments on mice and been shown to play essential role in synaptic plasticity and memory.
    1. Neuroscience

    Regulation of branching dynamics by axon-intrinsic asymmetries in Tyrosine Kinase Receptor signaling

    Marlen Zschätzsch, Carlos Oliva ... Bassem A Hassan
    Asymmetric localization of the receptor EGFR within branches of axons is required to establish the precise wiring of neuronal networks within the Drosophila brain.
    1. Cell Biology
    2. Plant Biology

    Subcellular and supracellular mechanical stress prescribes cytoskeleton behavior in Arabidopsis cotyledon pavement cells

    Arun Sampathkumar, Pawel Krupinski ... Elliot M Meyerowitz
    In the Arabidopsis epidermis, the internal mechanical stress of a cell competes with the external stress to control microtubule behavior, providing a framework to understand the mechanical feedbacks that underlie plant morphogenesis.
    1. Cell Biology

    Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution

    Jennifer L Mamrosh, Jae Man Lee ... David D Moore
    LRH-1/NR5A2 responds to ER stress by inducing a novel pathway that is required for stress resolution in mice and can be targeted by LRH-1 agonists.
    1. Cell Biology

    The influence of dynein processivity control, MAPs, and microtubule ends on directional movement of a localising mRNA

    Harish Chandra Soundararajan, Simon L Bullock
    In vitro reconstitution of mRNA motility reveals the basis of directionally biased motion by groups of motors, their response to potential obstacles, and the consequences of reaching microtubule ends.
    1. Chromosomes and Gene Expression

    The budding yeast Centromere DNA Element II wraps a stable Cse4 hemisome in either orientation in vivo

    Steven Henikoff, Srinivas Ramachandran ... Jorja G Henikoff
    A stable tetrameric nucleosome occupies the central segment of each ∼120-bp budding yeast centromere in two rotational phases of both reflectional orientations in vivo.
    1. Cell Biology
    2. Plant Biology

    FRET-based reporters for the direct visualization of abscisic acid concentration changes and distribution in Arabidopsis

    Rainer Waadt, Kenichi Hitomi ... Julian I Schroeder
    Fluorescent sensors can track the movement and distribution of the plant hormone abscisic acid in roots and leaves in Arabidopsis.
    1. Stem Cells and Regenerative Medicine

    Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria

    Carolyn E Adler, Chris W Seidel ... Alejandro Sánchez Alvarado
    A chemical method has been developed for studying single organ regeneration and fate specification of stem cells in an adult organism.
    1. Chromosomes and Gene Expression

    The nucleosomal barrier to promoter escape by RNA polymerase II is overcome by the chromatin remodeler Chd1

    Peter J Skene, Aaron E Hernandez ... Steven Henikoff
    The ATP-dependent chromatin remodeler Chd1 controls nucleosome turnover to allow RNA Polymerase to transcribe in vivo.
    1. Cell Biology
    2. Plant Biology

    Abscisic acid dynamics in roots detected with genetically encoded FRET sensors

    Alexander M Jones, Jonas ÅH Danielson ... Wolf B Frommer
    Fluorescent sensors for the hormone abscisic acid have been developed using a high-throughput platform, and used to monitor hormone dynamics in plant roots and leaves.
    1. Immunology and Inflammation

    T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks

    Karen E Tkach, Debashis Barik ... Grégoire Altan-Bonnet
    Experiment-driven quantitative model of IL-2 secretion demonstrates how T cells integrate their digital antigen responses into an analog-scaled output.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers

    Jessica E Scholey, Stanley Nithianantham ... Jawdat Al-Bassam
    The Bipolar Assembly domain of kinesin-5 comprises an anti-parallel four-helix bundle, which explains how kinesin-5 subunits assemble into bipolar tetramers with two motile ends that transmit forces while crosslinking and sliding adjacent microtubules during mitosis.
    1. Cell Biology
    2. Plant Biology

    Delivery of endocytosed proteins to the cell–division plane requires change of pathway from recycling to secretion

    Sandra Richter, Marika Kientz ... Gerd Jürgens
    The same membrane trafficking cargo can change pathways mediated by different members of ARF-GEF family of vesicle formation regulators.
    1. Stem Cells and Regenerative Medicine

    In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes

    Weida Li, Mio Nakanishi ... Qiao Zhou
    Combinations of transcription factors can convert pancreatic acinar cells into endocrine α-, β- and δ-cells in vivo.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Aim24 and MICOS modulate respiratory function, tafazzin-related cardiolipin modification and mitochondrial architecture

    Max Emanuel Harner, Ann-Katrin Unger ... Walter Neupert
    Interactions between Aim24 and the mitochondrial outer and inner membrane contact site complex (MICOS) are essential for mitochondrial ultrastructure, lipid composition and oxidative phosphorylation.
    1. Immunology and Inflammation

    Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells

    Dorothy K Sojka, Beatrice Plougastel-Douglas ... Wayne M Yokoyama
    Natural killer cells that were commonly thought to circulate around the body can actually reside in distinct tissues, such as in the liver, skin or uterus, and do not re-circulate.
    1. Neuroscience

    A frontal cortex event-related potential driven by the basal forebrain

    David P Nguyen, Shih-Chieh Lin
    Contrary to the common belief that cognitive event-related potentials are generated by local activity within the cerebral cortex, it is shown that some of these potentials are modulated by subcortical inputs.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Holocentromeres are dispersed point centromeres localized at transcription factor hotspots

    Florian A Steiner, Steven Henikoff
    Worm holocentromeres show a polycentric distribution, with each site containing a single centromeric nucleosome and also being targeted by multiple transcription factors.
    1. Structural Biology and Molecular Biophysics

    Encounter complexes and dimensionality reduction in protein–protein association

    Dima Kozakov, Keyong Li ... Sandor Vajda
    Analysis of protein–protein encounter complexes shows that proteins associate along preferred pathways, similar to the sliding of a protein along DNA.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA

    Erich G Chapman, Stephanie L Moon ... Jeffrey S Kieft
    The Dengue virus contains discretely folded RNA structures that confer the ability to resist a powerful host cell enzyme and produce a disease-inducing noncoding RNA.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    A conserved MCM single-stranded DNA binding element is essential for replication initiation

    Clifford A Froelich, Sukhyun Kang ... Eric J Enemark
    The crystal structure of the MCM helicase bound to single-stranded DNA reveals a binding motif that is critical for cell viability, helicase activation and DNA replication.
    1. Neuroscience

    Criticality and degeneracy in injury-induced changes in primary afferent excitability and the implications for neuropathic pain

    Stéphanie Ratté, Yi Zhu ... Steven A Prescott
    No single molecular change is uniquely necessary to cause neuropathic changes in primary afferent excitability; multiple different changes are sufficient.
    1. Structural Biology and Molecular Biophysics

    Phosphoinositide-mediated oligomerization of a defensin induces cell lysis

    Ivan KH Poon, Amy A Baxter ... Mark D Hulett
    A novel innate defense mechanism of cell lysis involves the coordinated oligomerization of a defensin by interaction with the membrane lipid, phosphatidylinositol 4,5-bisphosphate.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Bacterial autolysins trim cell surface peptidoglycan to prevent detection by the Drosophila innate immune system

    Magda Luciana Atilano, Pedro Matos Pereira ... Sérgio Raposo Filipe
    To avoid recognition by the immune system, bacteria use autolysins to trim fragments of peptidoglycans that are exposed on the bacterial cell wall.