1,242 research outputs found

    Alternative transcription start site selection leads to large differences in translation activity in yeast

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    mRNA levels do not accurately predict protein levels in eukaryotic cells. To investigate contributions of 5′ untranslated regions (5′ UTRs) to mRNA-specific differences in translation, we determined the 5′ UTR boundaries of 96 yeast genes for which in vivo translational efficiency varied by 80-fold. A total of 25% of genes showed substantial 5′ UTR heterogeneity. We compared the capacity of these genes' alternative 5′ UTR isoforms for cap-dependent and cap-independent translation using quantitative in vitro and in vivo translation assays. Six out of nine genes showed mRNA isoform-specific translation activity differences of greater than threefold in at least one condition. For three genes, in vivo translation activities of alternative 5′ UTR isoforms differed by more than 100-fold. These results show that changing genes' 5′ UTR boundaries can produce large changes in protein output without changing the overall amount of mRNA. Because transcription start site (TSS) heterogeneity is common, we suggest that TSS choice is greatly under-appreciated as a quantitatively significant mechanism for regulating protein production.National Institutes of Health (U.S.) (NIH grant GM081399

    Translation initiation factor eIF4G1 preferentially binds yeast transcript leaders containing conserved oligo-uridine motifs

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    Translational control of gene expression plays essential roles in cellular stress responses and organismal development by enabling rapid, selective, and localized control of protein production. Translational regulation depends on context-dependent differences in the protein output of mRNAs, but the key mRNA features that distinguish efficiently translated mRNAs are largely unknown. Here, we comprehensively determined the RNA-binding preferences of the eukaryotic initiation factor 4G (eIF4G) to assess whether this core translation initiation factor has intrinsic sequence preferences that may contribute to preferential translation of specific mRNAs. We identified a simple RNA sequence motif-oligo-uridine-that mediates high-affinity binding to eIF4G in vitro. Oligo(U) motifs occur naturally in the transcript leader (TL) of hundreds of yeast genes, and mRNAs with unstructured oligo(U) motifs were enriched in immunoprecipitations against eIF4G. Ribosome profiling following depletion of eIF4G in vivo showed preferentially reduced translation of mRNAs with long TLs, including those that contain oligo(U). Finally, TL oligo(U) elements are enriched in genes with regulatory roles and are conserved between yeast species, consistent with an important cellular function. Taken together, our results demonstrate RNA sequence preferences for a general initiation factor, which cells potentially exploit for translational control of specific mRNAs. Keywords: RNA binding; eIF4G; ribosome footprint profiling; transcript leaders; translation initiationNational Institutes of Health (U.S.) (Grant GM094303)National Institutes of Health (U.S.) (Grant GM081399)National Institutes of Health (U.S.) (Grant T32GM007287

    JULES-BE:Representation of bioenergy crops and harvesting in the Joint UK Land Environment Simulator vn5.1

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    We describe developments to the land surface model JULES, allowing for flexible user-prescribed harvest regimes of various perennial bioenergy crops or natural vegetation types. Our aim is to integrate the most useful aspects of dedicated bioenergy models into dynamic global vegetation models, in order that assessment of bioenergy options can benefit from state-of-the-art Earth system modelling. A new plant functional type (PFT) representing Miscanthus is also presented. The Miscanthus PFT fits well with growth parameters observed at a site in Lincolnshire, UK; however, global observed yields of Miscanthus are far more variable than is captured by the model, primarily owing to the model's lack of representation of crop age and establishment time. Global expansion of bioenergy crop areas under a 2 ?C emissions scenario and balanced greenhouse gas mitigation strategy from the IMAGE integrated assessment model (RCP2.6- SSP2) achieves a mean yield of 4.3 billion tonnes of dry matter per year over 2040-2099, around 30 % higher than the biomass availability projected by IMAGE. In addition to perennial grasses, JULES-BE can also be used to represent short-rotation coppicing, residue harvesting from cropland or forestry and rotation forestry

    U.S.-Mexico Risk Taskforce to Support the Health Supply Chain Systems for Infrastructure and Workforce Threatened by the COViD19 Pandemic

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    The purpose of this project was to integrate a binational Taskforce from Mexico and the U.S. that could serve as an advisory group to guide the identification and characterization of key variables and processes addressing the impact of COVID-19 in the state of risk of supply chains of critical value for trade between Mexico and the U.S. This project aimed as well as providing the best technology integrator to assimilate evidence that could facilitate the production of risk-based analytics to better inform stakeholders about the likely implementation of risk mitigating strategies that secure the optimal operation of supply chain systems involving trade between both countries. It aimed as well to produce a risk information system that would produce periodical information about the state of risk of Mexico and U.S. supply chain

    Biochemical and clinical characterization of metabolic phenotypes: a cross-sectional study from Maracaibo city, Venezuela [version 1; referees: awaiting peer review]

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    Background: In 1980, Reuben Andresen observed that in certain individuals, obesity did not increase mortality, introducing an atypical phenotype called “healthy obese”. Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. Methods: A descriptive, cross-sectional study with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. Results: In the studied population, 5.2% (n=64) corresponded to unhealthy lean subjects, and 17.4% (n=217) to healthy obese subjects. Metabolically unhealthy normal-weight (MUNW) phenotype was found in males in 53.3% in contrast to 51.3% of metabolically unhealthy obese (MUO) phenotype found in females. An association between metabolically unhealthy phenotypes and a higher risk of a coronary event was found, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Conclusion: Individuals with atypical metabolic phenotypes exist in Maracaibo city. Related factors may include insulin resistance, basal glucose levels, and triglycerides levels. Lastly, cardiovascular risk exhibited by healthy obese individuals should be classified in categories of major coronary risk related to lean subjects

    Photo-reverberation mapping of a protoplanetary accretion disk around a T Tauri star

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    Theoretical models and spectroscopic observations of newborn stars suggest that protoplantary disks have an inner 'wall' at a distance set by the disk interaction with the star. Around T Tauri stars, the size of this disk hole is expected to be on a 0.1 au scale that is unresolved by current adaptive optics imaging, though some model-dependent constraints have been obtained by near-infrared interferometry. Here we report the first measurement of the inner disk wall around a solar-mass young stellar object, YLW 16B in the ρ Ophiuchi star-forming region, by detecting the light-travel time of the variable radiation from the stellar surface to the disk. Consistent time lags were detected on two nights, when the time series in H (1.6 μm) and K (2.2 μm) bands were synchronized while the 4.5 μm emission lagged by 74.5 ± 3.2 s. Considering the nearly edge-on geometry of the disk, the inner rim should be 0.084 au from the protostar on average, with an error of order 0.01 au. This size is likely larger than the range of magnetospheric truncations and consistent with an optically and geometrically thick disk front at the dust sublimation radius at ∼1500 K. The widths of the cross-correlation functions between the data in different wavebands place possible new constraints on the geometry of the disk

    La Imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia en los departamentos del Atlántico, Bolívar, Cesar y Sucre

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    En el acompañamiento psicosocial en escenarios de violencia se ha desarrollado varias problemáticas en los contextos de violencia, donde se ha realizado una reflexión analítica desde el enfoque narrativo el caso de Amparo, video comisión de la verdad (2022, 13 de abril). Historias que retornan, y el caso Masacre en el Salado en el corregimiento el Carmen de Bolívar, relatos de resiliencia después de 20 años. (2020,11 de febrero), lo cual se da un análisis encontrando los emergentes psicosociales, los recursos de afrontamiento y la experiencia subjetiva de las víctimas, con el fin de facilitar la potenciación que se requiere en cada caso. En los relatos de vida propuestos se profundizan los hechos traumáticos donde se realizan unas preguntas orientadoras de manera colaborativa llevando la socialización, la contextualización al relato de Amparo. Comisión de la Verdad, lo cual narra su propia historia permitiendo conocer el empoderamiento y la transformación individual y colectiva frente a los hechos violentos vividos. Por otra parte, tenemos la experiencia de la Foto voz donde se realiza el proceso de lugares de comunidades que han vivido la violencia, por medio de la fotografía se reconoce la imagen narrativa que contribuye a los diferentes escenarios afectados y que a su vez se logra la reconstrucción social. Historias reales que marcan escenarios violentos a causa del poder adquisitivo de la fuerza de los grupos ilegales, generando una atención psicosocial prioritaria con la propuesta de estrategias que fortalezcan y brinden el acompañamiento a las víctimas con el objetivo de reparar sus vidas.In the diploma course to deepen psychosocial accompaniment in scenarios of violence,several problems have been developed in contexts of violence, where an analytical reflection hasbeen carried out from the narrative approach in the case of Amparo, video truth commission (2022, April 13 ). Stories that return, and the case of the Massacre in El Salado in the village of Carmen de Bolívar, stories of resilience after 20 years. (2020, February 11), in which an analysisis given finding the arising psychosocial points, the coping resources and the subjective experience of the victims, in order to facilitate the empowerment that is required in each case. In the proposed life stories, the traumatic events are further analyzed where some guiding questions are asked in a collaborative way, leading to socialization, contextualization to Amparo's story. Truth Commission, which narrates its own history allowing us to see the empowerment, individual and collective transformation in the face of the violent events that were experienced. On the other hand, we have the experience of the Photovoice where the process of places of communities that have experienced violence is carried out, through photography the narrative image that contributes to the different affected scenarios is recognized and, in turn, social reconstruction is achieved. Real stories that mark violent scenarios due to the purchasing power of the force ofillegal groups, generating priority psychosocial care with the proposal of strategies that strengthen and provide support to the victims with the aim of repairing their lives

    Nuevos enfoques moleculares en la regulación de la adipogénesis. El papel de la Conexina 43

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    La prevalencia de la obesidad a nivel mundial se ha incrementador&aacute;pidamente durante los &uacute;ltimos a&ntilde;os debido principalmentea los cambios en el estilo de vida de la poblaci&oacute;ncon un aumento significativo en el consumo de energ&iacute;a y disminuci&oacute;nde los niveles de actividad f&iacute;sica. Es por esto quela comunidad cient&iacute;fica est&aacute; interesada en comprender deforma m&aacute;s profunda los mecanismos que regulan la fisiopatolog&iacute;ade la obesidad. Dentro de los diferentes blancos deestudio se encuentra la adipog&eacute;nesis, cuyo entendimiento esfundamental para comprender el desarrollo de la obesidad ylas patolog&iacute;as asociadas a esta. Recientemente ha surgidoimportantes evidencias que involucran a la prote&iacute;na de canalesde &ldquo;Gap Junction&rdquo; conexina 43 (Cx43) en la regulaci&oacute;nde los procesos relacionados con adipog&eacute;nesis, cuyo papeles b&aacute;sicamente anti-adipog&eacute;nico, sin embargo, nuevas funcionesde Cx43 en la regulaci&oacute;n de la formaci&oacute;n del tejidoadiposo siguen descubri&eacute;ndose

    Implementation of trait-based ozone plant sensitivity in the Yale interactive terrestrial biosphere model v1.0 to assess global vegetation damage

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    A major limitation in modeling global ozone (O3) vegetation damage has long been the reliance on empiri- cal O3 sensitivity parameters derived from a limited num- ber of species and applied at the level of plant functional types (PFTs), which ignore the large interspecific variations within the same PFT. Here, we present a major advance in large-scale assessments of O3 plant injury by linking the trait leaf mass per area (LMA) and plant O3 sensitivity in a broad and global perspective. Application of the new ap- proach and a global LMA map in a dynamic global veg- etation model reasonably represents the observed interspe- cific responses to O3 with a unified sensitivity parameter for all plant species. Simulations suggest a contemporary global mean reduction of 4.8 % in gross primary productivity by O3, with a range of 1.1 %–12.6 % for varied PFTs. Hotspots with damage > 10 % are found in agricultural areas in the eastern US, western Europe, eastern China, and India, accompanied by moderate to high levels of surface O3. Furthermore, we simulate the distribution of plant sensitivity to O3, which is highly linked with the inherent leaf trait trade-off strategies of plants, revealing high risks for fast-growing species with low LMA, such as crops, grasses, and deciduous trees
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