940 research outputs found

    The Shine-Dalgarno sequence of riboswitch-regulated single mRNAs shows ligand-dependent accessibility bursts

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    In response to intracellular signals in Gram-negative bacteria, translational riboswitches—commonly embedded in messenger RNAs (mRNAs)—regulate gene expression through inhibition of translation initiation. It is generally thought that this regulation originates from occlusion of the Shine-Dalgarno (SD) sequence upon ligand binding; however, little direct evidence exists. Here we develop Single Molecule Kinetic Analysis of RNA Transient Structure (SiM-KARTS) to investigate the ligand-dependent accessibility of the SD sequence of an mRNA hosting the 7-aminomethyl-7-deazaguanine (preQ_1)-sensing riboswitch. Spike train analysis reveals that individual mRNA molecules alternate between two conformational states, distinguished by ‘bursts’ of probe binding associated with increased SD sequence accessibility. Addition of preQ_1 decreases the lifetime of the SD’s high-accessibility (bursting) state and prolongs the time between bursts. In addition, ligand-jump experiments reveal imperfect riboswitching of single mRNA molecules. Such complex ligand sensing by individual mRNA molecules rationalizes the nuanced ligand response observed during bulk mRNA translation

    Tratamiento asistido por artroscopia de las fracturas de radio distal

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    ResumenLa artroscopia proporciona una valoración directa de la superficie articular y permite detectar lesiones asociadas en las fracturas de la extremidad distal del radio. Su incorporación al tratamiento de estas fracturas ha supuesto un mejor control de la reducción de los trazos articulares, pero se trata de una técnica compleja que aún no está generalizada entre la mayoría de los cirujanos ortopédicos y/o de la mano y la muñeca.Se realiza una revisión y actualización de las ventajas, las indicaciones, las claves técnicas, los resultados y los datos científicos de su utilidad para el tratamiento de las fracturas del radio distal.AbstractArthroscopy provides a direct evaluation of the joint surface and enables associated injuries to be detected in fractures of the distal end of the radius. Although its incorporation into the treatment of these fractures has led to a better control in the reduction of joint traces, it is a complicated technique that is still not in general use by the majority of orthopaedic and/or hand and wrist surgeons.A review is presented here, as well as an update of the advantages, indications, the key techniques, results, and scientific data of its use in the treatment of distal radius fractures

    Rapid evolution of a floral trait following acquisition of novel pollinators

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    Changes in the pollinator assemblage visiting a plant can have consequences for reproductive success and floral evolution. We studied a recent plant trans‐continental range expansion to test whether the acquisition of new pollinator functional groups can lead to rapid adaptive evolution of flowers. In Digitalis purpurea, we compared flower visitors, floral traits and natural selection between native European populations and those in two Neotropical regions, naturalised after independent introductions. Bumblebees are the main pollinators in native populations while both bumblebees and hummingbirds are important visitors in the new range. We confirmed that the birds are effective pollinators and deposit more pollen grains on stigmas than bumblebees. We found convergent changes in the two new regions towards larger proximal corolla tubes, a floral trait that restricts access to nectar to visitors with long mouthparts. There was a strong positive linear selection for this trait in the introduced populations, particularly on the length of the proximal corolla tube, consistent with the addition of hummingbirds as pollinators. Synthesis. The addition of new pollinators is likely to happen often as humans influence the ranges of plants and pollinators but it is also a common feature in the long‐term evolution of the angiosperms. We show how novel selection followed by very rapid evolutionary change can be an important force behind the extraordinary diversity of flower

    RNA promotes the formation of spatial compartments in the nucleus

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    The nucleus is a highly organized arrangement of RNA, DNA, and protein molecules that are compartmentalized within three-dimensional (3D) structures involved in shared functional and regulatory processes. Although RNA has long been proposed to play a global role in organizing nuclear structure, exploring the role of RNA in shaping nuclear structure has remained a challenge because no existing methods can simultaneously measure RNA-RNA, RNA-DNA, and DNA-DNA contacts within 3D structures. To address this, we developed RNA & DNA SPRITE (RD-SPRITE) to comprehensively map the location of all RNAs relative to DNA and other RNAs. Using this approach, we identify many RNAs that are localized near their transcriptional loci (RNA-DNA) together with other diffusible ncRNAs (RNA-RNA) within higher-order DNA structures (DNA-DNA). These RNA-chromatin compartments span three major classes of nuclear functions: RNA processing (including ribosome biogenesis, mRNA splicing, snRNA biogenesis, and histone mRNA processing), heterochromatin assembly, and gene regulation. More generally, we identify hundreds of ncRNAs that form stable nuclear compartments in spatial proximity to their transcriptional loci. We find that dozens of nuclear compartments require RNA to guide protein regulators into these 3D structures, and focusing on several ncRNAs, we show that these ncRNAs specifically regulate heterochromatin assembly and the expression of genes contained within these compartments. Together, our results demonstrate a unique mechanism by which RNA acts to shape nuclear structure by forming high concentration territories immediately upon transcription, binding to diffusible regulators, and guiding them into spatial compartments to regulate a wide range of essential nuclear functions

    Single Molecule Cluster Analysis dissects splicing pathway conformational dynamics

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    The spliceosome is the dynamic RNA-protein machine responsible for faithfully splicing introns from precursor messenger RNAs (pre-mRNAs). Many of the dynamic processes required for the proper assembly, catalytic activation, and disassembly of the spliceosome as it acts on its pre-mRNA substrate remain poorly understood, a challenge that persists for many biomolecular machines. Here, we developed a fluorescence-based Single Molecule Cluster Analysis (SiMCAn) tool to dissect the manifold conformational dynamics of a pre-mRNA through the splicing cycle. By clustering common dynamic behaviors derived from selectively blocked splicing reactions, SiMCAn was able to identify signature conformations and dynamic behaviors of multiple ATP-dependent intermediates. In addition, it identified a conformation adopted late in splicing by a 3′ splice site mutant, invoking a mechanism for substrate proofreading. SiMCAn presents a novel framework for interpreting complex single molecule behaviors that should prove widely useful for the comprehensive analysis of a plethora of dynamic cellular machines

    Sistema on-line de predicción de emergencia de malezas

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    Con el objetivo de poner a disposición de productores y asesores agronómicos la información proporcionada por distintos modelos en tiempo real y de una manera amigable, se desarrolló una aplicación web que automatiza el cálculo de la emergencia empleando los pronósticos del tiempo de la región y presenta de manera gráfica las estimaciones en forma diaria y acumulada.Sociedad Argentina de Informática e Investigación Operativ

    Sistema on-line de predicción de emergencia de malezas

    Get PDF
    Con el objetivo de poner a disposición de productores y asesores agronómicos la información proporcionada por distintos modelos en tiempo real y de una manera amigable, se desarrolló una aplicación web que automatiza el cálculo de la emergencia empleando los pronósticos del tiempo de la región y presenta de manera gráfica las estimaciones en forma diaria y acumulada.Sociedad Argentina de Informática e Investigación Operativ

    The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress

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    Chronic social isolation causes severe psychological effects in humans, but their neural bases remain poorly understood. 2 weeks (but not 24 hr) of social isolation stress (SIS) caused multiple behavioral changes in mice and induced brain-wide upregulation of the neuropeptide tachykinin 2 (Tac2)/neurokinin B (NkB). Systemic administration of an Nk3R antagonist prevented virtually all of the behavioral effects of chronic SIS. Conversely, enhancing NkB expression and release phenocopied SIS in group-housed mice, promoting aggression and converting stimulus-locked defensive behaviors to persistent responses. Multiplexed analysis of Tac2/NkB function in multiple brain areas revealed dissociable, region-specific requirements for both the peptide and its receptor in different SIS-induced behavioral changes. Thus, Tac2 coordinates a pleiotropic brain state caused by SIS via a distributed mode of action. These data reveal the profound effects of prolonged social isolation on brain chemistry and function and suggest potential new therapeutic applications for Nk3R antagonists
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