Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome

WW domains are small domains present in many human proteins with a wide array of functions and acting through the recognition of proline-rich sequences. The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing. In this work we use high-field high-resolution NMR and enhanced sampling molecular dynamics simulations to gain insight into the molecular causes the disease. We find that the wild type protein is partially unfolded exchanging among multiple beta-strand-like conformations in solution. The Y65C mutation further destabilizes the residual fold and primes the protein for the formation of a disulphide bridge, which could be at the origin of the loss of function

Structure and functioning of a mountain grazed grassland and their response after exclosure

Se estudió el efecto del pastoreo por ganado doméstico y de distintos tiempos de exclusión sobre la composición florística y la diversidad, y sobre la dinámica de la biomasa aérea, el contenido de nitrógeno y la productividad primaria de diferentes formas de vida, en un pastizal semi-natural de montaña de la provincia de Córdoba. El pastoreo promovió una mayor diversidad de especies, aunque la biomasa total y la productividad fueron máximas en el sitio con mayor tiempo de exclusión. El pastoreo promovió la abundancia de especies rastreras y graminoides. Las gramíneas en penacho sólo aparecen a partir de los 4 años de exclusión y representan más del 90% de la biomasa total en el sitio excluido del pastoreo por 15 años. No hubo diferencias significativas en la dinámica estacional de la biomasa en pie ni del nitrógeno de las diferentes formas de crecimiento en los diferentes sitios estudiados, pero las formas de crecimiento rastreras y graminoides prolongaron su estación de crecimiento bajo pastoreo, y se observó un mayor contenido de nitrógeno en las plantas pastoreadas. La productividad primaria neta aérea estuvo limitada a la primavera y el verano, entre los meses de octubre y marzo. La productividad disminuyó ligeramente luego de la exclusión del pastizal, pero aumentó significativamente a partir de los 4 años sin pastoreo.The effect of grazing and different times of exclosure on floristic composition, biomass, plant nitrogen concentration and aboveground net plant productivity were studied in a mountain grassland of Córdoba, Argentina. Plant diversity was maximum at the grazed site and no invasion of alien species was recorded at any site, but total standing biomass and aboveground net plant productivity were maximum at the site excluded from grazing for 15 years. Prostrate, graminoid and annual growth forms accounted for more than 90% of live biomass at the grazed site. Rosettes increased their biomass with grazing exclusion and tussock grasses were apparent only after 4 years of exclusion and accounted for 90% of total biomass after 15 years of exclosure. There was no site effect on seasonal dynamics of standing biomass and plant nitrogen content of different plant growth forms, but prostrates and graminoids showed a prolonged growth season under grazing, and plant nitrogen content was higher in grazed plants. Aboveground net plant productivity (ANPP) was limited to spring and summer, from October to March. Two years of exclusion from grazing slightly decreased ANPP, but significatively increased after 4 years without livestock grazing.Universidad Nacional de La Plata (UNLP) - Facultad de Ciencias Agrarias y Forestales (FCAF

An Allosteric Cross-Talk Between the Activation Loop and the ATP Binding Site Regulates the Activation of Src Kinase

Phosphorylation of the activation loop is a fundamental step in the activation of most protein kinases. In the case of the Src tyrosine kinase, a prototypical kinase due to its role in cancer and its historic importance, phosphorylation of tyrosine 416 in the activation loop is known to rigidify the structure and contribute to the switch from the inactive to a fully active form. However, whether or not phosphorylation is able per-se to induce a fully active conformation, that efficiently binds ATP and phosphorylates the substrate, is less clear. Here we employ a combination of solution NMR and enhanced-sampling molecular dynamics simulations to fully map the effects of phosphorylation and ATP/ADP cofactor loading on the conformational landscape of Src tyrosine kinase. We find that both phosphorylation and cofactor binding are needed to induce a fully active conformation. What is more, we find a complex interplay between the A-loop and the hinge motion where the phosphorylation of the activation-loop has a significant allosteric effect on the dynamics of the C-lobe

Factores de éxito en las empresas de la región sureste de México

The success of micro and small enterprises (MyPE) positively influences the competitiveness and economic growth of a region, so that this research was conducted with the objective of identifying the factors that affect the permanence of the MyPE of the region. tertiary sector in the southeast region of Mexico; case study of the TUXTLAS region. This article details the methodology used in the research using a quantitative approach and the type of descriptive study, for this we proceeded to develop an instrument which was applied to the three main municipalities that make up the Tuxtlas region, considering a population of 4874 MyPE, of which a sample of 253 micro and small businesses was determined, so 65 correspond to the municipality of Catemaco, 145 to San Andrés Tuxtla, and 43 to Santiago Tuxtla. With this research, it was possible to identify that internal control, marketing strategies and strategic planning are key aspects for the permanence of the MyPE in the Southeast region of Mexico.El éxito de las micro y pequeñas empresas (MyPE) influye de manera positiva en la competitividad y crecimiento económico de una región, de tal manera que la presente investigación se realizó con el objetivo de identificar los factores que inciden en la permanencia de las MyPE del sector terciario en la región sureste de México; caso de estudio región de los TUXTLAS.  En este artículo se detalla la metodología utilizada en la investigación utilizando un enfoque cuantitativo y el tipo de estudio descriptivo, para ello se procedió a elaborar un instrumento el cual fue aplicado a los tres principales municipios que integran la región de los Tuxtlas, considerando una población de 4874 MyPE, de la cuales se determinó una muestra de 253 micro y pequeñas empresas, por lo que 65 corresponden al municipio de Catemaco, 145 a San Andrés Tuxtla, y 43 a Santiago Tuxtla. Con esta investigación se logró identificar que el control interno, las estrategias de comercialización y la planeación estratégica son aspectos claves para la permanencia de las MyPE en la región Sureste de México

Factores de éxito en las empresas de la región sureste de México

El éxito de las micro y pequeñas empresas (MyPE) influye de manera positiva en la competitividad y crecimiento económico de una región, de tal manera que la presente investigación se realizó con el objetivo de identificar los factores que inciden en la permanencia de las MyPE del sector terciario en la región sureste de México; caso de estudio región de los TUXTLAS. En este artículo se detalla la metodología utilizada en la investigación utilizando un enfoque cuantitativo y el tipo de estudio descriptivo, para ello se procedió a elaborar un instrumento el cual fue aplicado a los tres principales municipios que integran la región de los Tuxtlas, considerando una población de 4874 MyPE, de la cuales se determinó una muestra de 253 micro y pequeñas empresas, por lo que 65 corresponden al municipio de Catemaco, 145 a San Andrés Tuxtla, y 43 a Santiago Tuxtla. Con esta investigación se logró identificar que el control interno, las estrategias de comercialización y la planeación estratégica son aspectos claves para la permanencia de las MyPE en la región Sureste de México

Revealing full chemical forms of lead in wine with combined XRF-NMR technologies

Since 1953, The World Organization of Vine and Wine (OIV) Member States have reduced the lead maximum limits (ML) in wines, down to 0.05 mg/L (2018). Evidently, this ML value is too restrictive for wine industry as it excludes from international market a significant portion of wine production. Currently, the Codex Committee on Contaminants in Foods and OIV had recognized the value of gathering robust and novel data to better assess the best lowest ML for wine industry. Currently, there is not a direct statement within international reference documents, of which chemical form of lead must be controlled and/ or reduced. This work presents for the first time a method combining Energy Dispersive X-Ray analysis (EDAX) and Nuclear Magnetic Resonance (NMR) spectroscopies in order to determine presence and concentrations of major and trace elements of lead and other element moieties in wine that can allow to better redefine lead's ML. By identification of K, L, M, radiation shells with additional αβi labelling of lead's major and minor components with semi-quantitative XRF, combined with chemical-shift analysis of inorganic Pb4+, Pb2+ and/or organo-lead within wine samples, we propose a full discrimination framework to disentangle and quantify different chemical forms of lead

Corporate Social Responsibility Strategies of Spanish Listed Firms and Controlling Shareholders’ Representatives

This article aims at analyzing how controlling shareholders’ representatives on boards affect corporate social responsibility (CSR) strategies (disclosing CSR matters) in Spain, a context characterized by high ownership concentration, one-tier boards, little board independence, weak legal protection for investors, and the presence of large shareholders, especially institutional shareholders. Furthermore, among controlling shareholders’ representatives, we can distinguish between those appointed by insurance companies and banks and those appointed by mutual funds, investment funds, and pension funds. The effect of these categories of directors on CSR strategies is, therefore, also analyzed. Our findings suggest that controlling shareholders’ representatives have a positive effect on CSR strategies, as do directors appointed by investment funds, pension funds, and mutual funds, while directors appointed by banks and insurance companies have no impact on CSR strategies. This analysis offers new insights into the role played by certain types of directors on CSR strategies

Female Institutional Directors on Boards and Firm Value

The aim of this research is to examine what impact female institutional directors on boards have on corporate performance. Previous research shows that institutional female directors cannot be considered as a homogeneous group since they represent investors who may or may not maintain business relations with the companies on whose corporate boards they sit. Thus, it is not only the effect of female institutional directors as a whole on firm value that has been analysed, but also the impact of pressure-resistant female directors, who represent institutional investors (investment, pension and mutual funds) that only invest in the company, and do not maintain a business relation with the firm. We hypothesize that there is a non-linear association, specifically quadratic, between institutional and pressure-resistant female directors on boards and corporate performance. Our results report that female institutional directors on boards enhance corporate performance, but when they reach a certain threshold on boards (11.72 %), firm value decreases. In line with female institutional directors, pressure-resistant female directors on boards also increase firm value, but only up to a certain figure (12.71 % on boards), above which they have a negative impact on firm performance. These findings are consistent with an inverted U-shaped relationship between female institutional directors and pressure-resistant female directors and firm performance