A link between transcription fidelity and pausing in vivo

Pausing by RNA polymerase is a major mechanism that regulates transcription elongation but can cause conflicts with fellow RNA polymerases and other cellular machineries. Here, we summarize our recent finding that misincorporation could be a major source of transcription pausing in vivo, and discuss the role of misincorporation-induced pausing

Misincorporation by RNA polymerase is a major source of transcription pausingin vivo

The transcription error rate estimated from mistakes in end product RNAs is 10−3–10−5. We analyzed the fidelity of nascent RNAs from all actively transcribing elongation complexes (ECs) in Escherichia coli and Saccharomyces cerevisiae and found that 1–3% of all ECs in wild-type cells, and 5–7% of all ECs in cells lacking proofreading factors are, in fact, misincorporated complexes. With the exception of a number of sequence-dependent hotspots, most misincorporations are distributed relatively randomly. Misincorporation at hotspots does not appear to be stimulated by pausing. Since misincorporation leads to a strong pause of transcription due to backtracking, our findings indicate that misincorporation could be a major source of transcriptional pausing and lead to conflicts with other RNA polymerases and replication in bacteria and eukaryotes. This observation implies that physical resolution of misincorporated complexes may be the main function of the proofreading factors Gre and TFIIS. Although misincorporation mechanisms between bacteria and eukaryotes appear to be conserved, the results suggest the existence of a bacteria-specific mechanism(s) for reducing misincorporation in protein-coding regions. The links between transcription fidelity, human disease, and phenotypic variability in genetically-identical cells can be explained by the accumulation of misincorporated complexes, rather than mistakes in mature RNA

A digital literary magazine to develop the critical thinking of students from modern languages program at universidad ECCI in a multilingual context

Within the arrival of the new worldwide context, literature has been one of the most useful tools in order to communicate with people. Also, to express the different ideals and thoughts of the different writers overseas. Most of them were writers in magazines and this one, being part of the human progress and being one of the first literary entertainments allowed the improvement of writing and reading. Along with the advancement of technology they permitted to the magazines being part of the digital world and being accessible to everyone. The purpose of this Digital Literary Magazine is to foster the features of critical thinking, reading and writing in the students and professors of Universidad ECCI and to show the different types of handwritten art and the skills that can being improved.Abstract Resumen List of tables Introduction Justification Statement of the problem Objectives General Objective Specifics Objectives Background Theoretical framework Literary Magazine Digital Magazine Multilingual Context Critical Thinking Writing Reading Methodology Approach Method Descriptive Research Type Instrument Population and Sample Data analysis Interview Analysis Survey Analysis Focus Group Analysis Conclusions Annexes Survey Focus Group Interview Bibliography WebgraphyPregradoProfesional en Lenguas ModernasLenguas Moderna

Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women’s empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and wome

Control of transcription elongation by GreA determines rate of gene expression in Streptococcus pneumoniae

Transcription by RNA polymerase may be interrupted by pauses caused by backtracking or misincorporation that can be resolved by the conserved bacterial Gre-factors. However, the consequences of such pausing in the living cell remain obscure. Here, we developed molecular biology and transcriptome sequencing tools in the human pathogen Streptococcus pneumoniae and provide evidence that transcription elongation is rate-limiting on highly expressed genes. Our results suggest that transcription elongation may be a highly regulated step of gene expression in S. pneumoniae. Regulation is accomplished via long-living elongation pauses and their resolution by elongation factor GreA. Interestingly, mathematical modeling indicates that long-living pauses cause queuing of RNA polymerases, which results in 'transcription traffic jams' on the gene and thus blocks its expression. Together, our results suggest that long-living pauses and RNA polymerase queues caused by them are a major problem on highly expressed genes and are detrimental for cell viability. The major and possibly sole function of GreA in S. pneumoniae is to prevent formation of backtracked elongation complexes

Financial Stability Report - Second Semester of 2021

Banco de la República’s main objective is to preserve the purchasing power of the currency in coordination with the general economic policy that is intended to stabilize output and employment at long-term sustainable levels. Properly meeting the goal assigned to the Bank by the 1991 Constitution critically depends on preserving financial stability. This is understood to be a general condition in which the financial system assesses and manages the financial risks in a way that facilitates the economy’s performance and efficient allocation of resources while, at the same time, it is able to, on its own, absorb, dissipate, and mitigate the shocks that may arise as a result of adverse events. This Financial Stability Report meets the goal of giving Banco de la República’s diagnosis of the financial system’s and its debtors’ recent performance as well as of the main risks and vulnerabilities that could affect the stability of the Colombian economy. In this way, participants in financial markets and the public are being informed, and public debate on trends and risks affecting the system is being encouraged. The results presented here also serve the monetary authority as a basis for making decisions that will enhance financial stability in the general context of its objectives. In recent months, several positive aspects of the financial system have preserved a remarkable degree of continuity and stability: the liquidity and capital adequacy of financial institutions have remained well above the regulatory minimums at both the individual and consolidated levels, the coverage of past-due loans by loan-loss provisions remains high, and the financial markets for public and private debt and stocks have continued to function normally. At the same time, a surge in all the types of loan portfolios, a sharp downturn in the non-performing loan portfolio, and a rise in the profitability of credit institutions can be seen for the first time since the beginning of the pandemic. In line with the general recovery of the economy, the main vulnerability to the stability of the Colombian financial system identified in the previous edition—uncertainty about changes in the non-performing loans portfolio—has receded and remains on a downward trend. In this edition, the main source of vulnerability identified for financial stability in the short term is the system’s exposure to sudden changes in international financial conditions; the results presented in this Report indicate that the system is sufficiently resilient to such scenarios. In compliance with its constitutional objectives and in coordination with the financial system’s security network, Banco de la República will continue to closely monitor the outlook for financial stability at this juncture and will make the decisions necessary to ensure the proper functioning of the economy, facilitate the flow of sufficient credit and liquidity resources, and further the smooth functioning of the payment system. Leonardo Villar Gomez Governor Box 1 -Decomposition of the Net Interest Margin in Colombia and Chile Wilmar Cabrera Daniela Rodríguez-Novoa Box 2 - Spatial Analysis of New Home Prices in Bogota, Medellín, and Cali Using a Geostatistical Approach María Fernanda Meneses Camilo Eduardo Sánchez Box 3 - Interest Rate Model for the SYSMO Stress Test Exercise Wilmar Cabrera Diego Cuesta Santiago Gamba Camilo Gómez Box 4 - The Transition from LIBOR and other International Benchmark Rates Daniela X. Gualtero Briceño Javier E. Pirateque Niñ

Reporte Estabilidad Financiera - Primer Semestre de 2020

In the face of the multiple shocks currently experienced by the domestic economy (resulting from the drop in oil prices and the appearance of a global pandemic), the Colombian financial system is in a position of sound solvency and adequate liquidity. At the same time, credit quality has been recovering and the exposure of credit institutions to firms with currency mismatches has declined relative to previous episodes of sudden drops in oil prices. These trends are reflected in the recent fading of red and blue tonalities in the performance and credit risk segments of the risk heatmaps in Graphs A and B.1 Naturally, the sudden, unanticipated change in macroeconomic conditions has caused the appearance of vulnerabilities for short-term financial stability. These vulnerabilities require close and continuous monitoring on the part of economic authorities. The main vulnerability is the response of credit and credit risk to a potential, temporarily extreme macroeconomic situation in the context of: (i) recently increased exposure of some banks to household sector, and (ii) reductions in net interest income that have led to a decline in the profitability of the banking business in the recent past. Furthermore, as a consequence of greater uncertainty and risk aversion, occasional problems may arise in the distribution of liquidity between agents and financial markets. With regards to local markets, spikes have been registered in the volatility of public and private fixed income securities in recent weeks that are consistent with the behavior of the international markets and have had a significant impact on the liquidity of those instruments (red portions in the most recent past of some market risk items on the map in Graph A). In order to adopt a forward-looking approach to those vulnerabilities, this Report presents a stress test that evaluates the resilience of credit institutions in the event of a hypothetical scenario thatseeks to simulate an extreme version of current macroeconomic conditions. The scenario assumes a hypothetical negative growth that is temporarily strong but recovers going into the middle of the coming year and has extreme effects on credit quality. The results suggest that credit institutions have the ability to withstand a significant deterioration in economic conditions in the short term. Even though there could be a strong impact on credit, liquidity, and profitability under the scenario being considered, aggregate capital ratios would probably remain at above their regulatory limits over the horizon of a year. In this context, the recent measures taken by both Banco de la República and the Office of the Financial Superintendent of Colombia that are intended to help preserve the financial stability of the Colombian economy become highly relevant. In compliance with its constitutional objectives and in coordination with the financial system’s security network, Banco de la República will continue to closely monitor the outlook for financial stability at this juncture and will make the decisions that are necessary to ensure the proper functioning of the economy, facilitate the flow of sufficient credit and liquidity resources, and further the smooth functioning of the payment system. Juan José Echavarría Governo

Financial Stability Report - Second Semester of 2020

The Colombian financial system has not suffered major structural disruptions during these months of deep economic contraction and has continued to carry out its basic functions as usual, thus facilitating the economy's response to extreme conditions. This is the result of the soundness of financial institutions at the beginning of the crisis, which was reflected in high liquidity and capital adequacy indicators as well as in the timely response of various authorities. Banco de la República lowered its policy interest rates 250 points to 1.75%, the lowest level since the creation of the new independent bank in 1991, and provided ample temporary and permanent liquidity in both pesos and foreign currency. The Office of the Financial Superintendent of Colombia, in turn, adopted prudential measures to facilitate changes in the conditions for loans in effect and temporary rules for rating and loan-loss provisions. Finally, the national government expanded the transfers as well as the guaranteed credit programs for the economy. The supply of real credit (i.e. discounting inflation) in the economy is 4% higher today than it was 12 months ago with especially marked growth in the housing (5.6%) and commercial (4.7%) loan portfolios (2.3% in consumer and -0.1% in microloans), but there have been significant changes over time. During the first few months of the quarantine, firms increased their demands for liquidity sharply while consumers reduced theirs. Since then, the growth of credit to firms has tended to slow down, while consumer and housing credit has grown. The financial system has responded satisfactorily to the changes in the respective demands of each group or sector and loans may grow at high rates in 2021 if GDP grows at rates close to 4.6% as the technical staff at the Bank expects; but the forecasts are highly uncertain. After the strict quarantine implemented by authorities in Colombia, the turmoil seen in March and early April, which was evident in the sudden reddening of macroeconomic variables on the risk heatmap in Graph A,[1] and the drop in crude oil and coal prices (note the high volatility registered in market risk for the region on Graph A) the local financial markets stabilized relatively quickly. Banco de la República’s credible and sustained policy response played a decisive role in this stabilization in terms of liquidity provision through a sharp expansion of repo operations (and changes in amounts, terms, counterparties, and eligible instruments), the purchases of public and private debt, and the reduction in bank reserve requirements. In this respect, there is now abundant aggregate liquidity and significant improvements in the liquidity position of investment funds. In this context, the main vulnerability factor for financial stability in the short term is still the high degree of uncertainty surrounding loan quality. First, the future trajectory of the number of people infected and deceased by the virus and the possible need for additional health measures is uncertain. For that reason, there is also uncertainty about the path for economic recovery in the short and medium term. Second, the degree to which the current shock will be reflected in loan quality once the risk materializes in banks’ financial statements is uncertain. For the time being, the credit risk heatmap (Graph B) indicates that non-performing and risky loans have not shown major deterioration, but past experience indicates that periods of sharp economic slowdown eventually tend to coincide with rises in non-performing loans: the calculations included in this report suggest that the impact of the recession on credit quality could be significant in the short term. This is particularly worrying since the profitability of credit establishments has been declining in recent months, and this could affect their ability to provide credit to the real sector of the economy. In order to adopt a forward-looking approach to this vulnerability, this Report presents several stress tests that evaluate the resilience of the liquidity and capital adequacy of credit institutions and investment funds in the event of a hypothetical scenario that seeks to simulate an extreme version of current macroeconomic conditions. The results suggest that even though there could be strong impacts on the credit institutions’ volume of credit and profitability under such scenarios, aggregate indicators of total and core capital adequacy will probably remain at levels that are above the regulatory limits over the horizon of a year. At the same time, the exercises highlight the high capacity of the system's liquidity to face adverse scenarios. In compliance with its constitutional objectives and in coordination with the financial system's security network, Banco de la República will continue to closely monitor the outlook for financial stability at this juncture and will make the decisions that are necessary to ensure the proper functioning of the economy, facilitate the flow of sufficient credit and liquidity resources, and further the smooth operation of the payment systems. Juan José Echavarría Governo

Participación laboral en espondiloartritis axial radiográfica y no radiográfica

Introducción: las limitaciones laborales son un punto importante a considerar en el tratamiento de la espondiloartritis axial (EspAax) dado que esta enfermedad afecta a las personas en la etapa más productiva de la vida. Objetivos: describir la situación laboral en pacientes con EspAax de Argentina, incluyendo la espondilitis anquilosante (EA) y la espondiloartritis axial no radiográfica (EspAax-nr), y evaluar los factores asociados a la pérdida de productividad laboral (PPL) en esta cohorte nacional y los factores asociados a estar empleado

Reporte de Estabilidad Financiera - II semestre 2020

El sistema financiero colombiano no ha sufrido mayores traumatismos estructurales durante estos meses de profunda contracción económica, y ha continuado prestando con normalidad sus funciones básicas, facilitando la respuesta de la economía a condiciones extremas. Ello es el resultado de la solidez de las entidades financieras al inicio de la crisis, reflejada en elevados indicadores de liquidez y solvencia, y de la oportuna respuesta de distintas entidades. El Banco de la República redujo 250 puntos sus tasas de interés de política, hasta 1,75%, el menor nivel desde la creación del nuevo Banco independiente en 1991, y otorgó amplia liquidez transitoria y permanente, tanto en pesos como en moneda extranjera. Por su parte, la Superintendencia Financiera de Colombia adoptó medidas prudenciales para facilitar cambios en las condiciones de los créditos vigentes y reglas transitorias de calificación y constitución de provisiones. Finalmente, el Gobierno Nacional expandió las transferencias y los programas de créditos garantizados a la economía. El acervo de crédito real (i.e. descontando la inflación) en la economía supera hoy en 4% el de hace 12 meses, con crecimientos especialmente marcados en la cartera de vivienda (5,6%) y comercial (4,7%) (2,3% en consumo y -0,1% en microcrédito), pero ha habido cambios importantes en el tiempo. En los meses iniciales de la cuarentena las firmas elevaron fuertemente sus demandas por liquidez, y los consumidores las redujeron, mientras que en los meses recientes la dinámica del crédito a las firmas ha tendido a desacelerarse, y la del crédito a los consumidores y a la vivienda ha crecido. El sistema financiero ha respondido satisfactoriamente a la evolución de la demanda relativa de cada grupo o sector, y el crédito posiblemente crecerá a tasas altas en 2021 si el PIB crece a tasas cercanas a 4,6% como lo espera el equipo técnico del Banco, pero los pronósticos son altamente inciertos. Luego de la fuerte cuarentena implementada por las autoridades en Colombia, las turbulencias observadas en marzo y comienzos de abril, evidentes en el enrojecimiento repentino de variables macroeconómicas en el mapa de riesgos del Gráfico A , y la caída en los precios del petróleo y el carbón (nótese las altas volatilidades registradas en la región de riesgo de mercado del Gráfico A), los mercados financieros locales se estabilizaron con relativa rapidez. En esta estabilización tuvo un papel determinante la respuesta de política creíble y sostenida del Banco de la República en lo referente a la provisión de liquidez, con una fuerte expansión de operaciones repo (y variaciones en montos, plazos, contrapartes e instrumentos admisibles), la compra definitiva de deuda pública y privada, y la reducción del encaje de los bancos. En este sentido, hoy se observa abundante liquidez agregada y mejoras importantes en la posición de liquidez de los fondos de inversión colectiva. En este contexto, el principal factor de incertidumbre para la estabilidad financiera en el corto plazo continúa siendo el alto grado de incertidumbre que rodea a la calidad de la cartera. En primer lugar, es incierta la trayectoria futura del número de contagiados y fallecidos como consecuencia del virus y la eventual necesidad de medidas sanitarias adicionales. Por tal razón, también existe incertidumbre sobre la senda de recuperación de la economía en el corto y mediano plazo. En segundo lugar, es incierto el grado en que el choque actual se reflejará en la calidad de la cartera una vez se materialice el riesgo en los estados financieros. De momento, el mapa de riesgos (Gráfico B) indica que la cartera vencida y la cartera riesgosa no han mostrado mayores deterioros, pero la experiencia histórica indica que períodos de fuerte desaceleración económica tienden a coincidir eventualmente con aumentos de la cartera vencida: los cálculos incluidos en este reporte sugieren que el impacto de la recesión sobre la calidad del crédito en el corto plazo podría ser significativo. Ello es particularmente preocupante teniendo en cuenta que la rentabilidad de los establecimientos de crédito ha venido reduciéndose en meses recientes, lo cual podría afectar su capacidad para otorgar crédito al sector real de la economía. Con el fin de adoptar un enfoque prospectivo de cara a las vulnerabilidades identificadas, este reporte presenta varios ejercicios de sensibilidad (stress tests) que evalúan la resiliencia de la liquidez y la solvencia de los establecimientos de crédito y de los fondos de inversión colectiva ante escenarios hipotéticos que buscan aproximarse a una versión extrema de las condiciones económicas actuales. Los resultados sugieren que, en tales escenarios, se observarían fuertes impactos sobre el volumen de crédito y la rentabilidad de los establecimientos de crédito, aunque los indicadores agregados de solvencia total y básica permanecerían en niveles superiores a los límites regulatorios durante el horizonte de los ejercicios. Al tiempo, los ejercicios resaltan la alta capacidad que tiene la liquidez del sistema para enfrentar escenarios adversos. En cumplimiento de sus objetivos constitucionales y en coordinación con la red de seguridad del sistema financiero, el Banco de la República continuará monitoreando de cerca el panorama de estabilidad financiera en esta coyuntura y tomará aquellas decisiones que sean necesarias para garantizar el adecuado funcionamiento de la economía, facilitar los flujos de recursos suficientes de crédito y liquidez, y promover el buen funcionamiento del sistema de pagos. Juan José Echavarría Gerente GeneralRecuadro 1. Consideraciones de largo plazo sobre el acceso temprano al ahorro pensional en Colombia. Autores: Javier E. Pirateque Niño - Daniela X. Gualtero Briceño*Recuadro 2. Indicador de salud financiera para Colombia. Autores: Juan Sebastián Lemus Esquivel - Laura Viviana León Díaz*Recuadro 3. Ejercicios de estrés en tiempos de Covid-19. Autores: Angélica Lizarazo Cuéllar - María Fernanda Meneses*Recuadro 4. Principales medidas tomadas por algunos bancos centrales para canalizar crédito al sector real durante la pandemia. Autor: Daniela X. Gualtero Briceño*Sombreado 1. Efectos de los alivios otorgados a deudores en el marco de la emergencia por el Covid-19. Autor: Eduardo Yanquen