Tamaño crítico: efectos e implicaciones en crecimiento y ciclo celular

[spa] En Ia levadura de gemación el tamaño celular en START o tamaño crítico está determinado por Ia velocidad de crecimiento en G1. Durante esta fase, Saccharomyces cerevisiae presenta una disminución de Ia relación area superficie/volumen con el tamaño. En cambio, en el memento de Ia gemación se observa Ia existencia de un pico máximo en Ia velocidad de síntesis de Ia superficie celular, necesitando un gran aumento en Ia síntesis de materiales de Ia membrana plasmática y Ia pared celular, y un óptimo transporte de esos componentes hacia Ia yema para el correcto crecimiento de ésta. Por todo ello, postulamos Ia hipótesis de que Ia determinación del tamaño celular en START tendría importantes implicaciones en el óptimo crecimiento y desarrollo de Ia yema en las fases S-G2 del ciclo celular de levaduras. Para comprobar esta idea, realizamos un cuidadoso estudio delcrecimiento en S-G2 y observamos que Ia velocidad de crecimiento de Ia yema no aumenta de manera proporcional al tamaño de Ia célula madre,especialmente a volúmenes muy grandes. Ella no sucedía durante G1, donde observamos que Ia velocidad de crecimiento es proporcional al tamaño celular, según las !eyes del crecimiento exponencial. De modo muy notable, dicho efecto tampoco fue observado en células diploides y tetraploides, donde el tamaño es progresivamente mayor, pero proporcional al DNA genómico. Estos datos sugerían que Ia baja eficiencia de crecimiento de las células madre haploides de gran tamaño podría ser causada por algún tipo de insuficiencia génica. Por ejemplo, si Ia expresión de algunos genes importantes en crecimiento no escalase con el tamaño, se producirían cantidades limitantes de las proteínas codificadas y, por tanto, Ia eficiencia de los procesos correspondientes se vería seriamente comprometida. El crecimiento de Ia yema depende del transporte de vesículas desde Ia célula madre,y observamos que dicho transporte no aumentaba proporcionalmente al volumen de Ia célula madre.Sin embargo, el transportador de vesículas Myo2 no mostró una expresión disminuida y tampoco observamos una deficiencia en el número de cables de actina en células grandes, indicando que el sistema de transporte en sí no era limitante. Por dichas razones concluimos que el problema podría residir en el contenido de las vesículas, el cargo.Por tanto,estudiamos proteínas representativas del crecimiento en G1/S,y descubrimos que su nivel disminuye con el tamaño. Como pieza central de este trabajo, comparamos los transcriptomas de células pequeñas y grandes en G1/S, y encontramos muchos genes de categorías funcionales específicas que se regulan al alza o a Ia baja en células grandes en comparación con células pequeñas.Entre ellos encontramos genes relacionados con el crecimiento apical, el transporte de vesículas,el citoesqueleto,y Ia biogénesis ribosómica, que representa un coste energético extraordinario y debe estar muy bien regulada para un crecimiento óptimo. Finalmente, para genes paradigmáticos en estas categorías,realizamos un análisis cuidadoso de Ia insuficiencia génica y confirmamos sus efectos limitantes sobre el crecimiento de Ia yema. En resumen, nuestros resultados demuestran que S. cerevisiae ha establecido un tamaño crítico para lograr el crecimiento óptimo de Ia yema. A tamaños inusualmente mayores, Ia expresión de genes relacionados con proteínas ribosómicas, así como componentes esenciales del crecimiento apical, se reduce claramente produciendo una seria limitación del crecimiento celular.[eng] In budding yeast,cell size at START or the critical size is determined by the growth rate in G.l During this phase, Saccharomyces cerevisiae shows a decrease in the surface area/volume ratio as it increases in size.When the cell shifts from isotropic growth during Gl to polarized growth from the mother cell to the bud,surface synthesis rate peaks right after budding,where a great increase in plasma membrane and cell wall synthesis,and an optimal transport of these components to the bud,is necessary to grow as efficiently as possible. Therefore, we hypothesized that cell size set at START would have important implications for the optimal growth and development of the bud in the S-G2 phases of the yeast cell cycle. To test this notion,we carefully analyzed growth kinetics in S-G2 phases and observed that the growth rate of the bud does not increase proportionally to the mother cell size, particularly at very large cell volumes.This effect did not take place during Gl,where we found that growth rate is proportional to cell size, exquisitely following the rules of exponential growth. Notably, the abovementioned effect was not observed either in diploid or tetraploid cells where mother cell size is progressively larger,but proportional to genomic DNA. These data suggested that low growing efficiencies of large haploid mother cells could be caused by some sort of gene insufficiency.For instance,if expression of some genes playing prominent roles in bud growth would not scale with size,rate-limiting amounts of the encoded proteins would be produced and,hence,the efficiency of the corresponding processes would be seriously compromised. One of the most important mechanisms for bud growth is the transport of vesicles from the mother cell. Indeed,we observed problems in transport,because it did not occur at a rate proportional to mother cell volume.However, it was not a matter of the transport machinery itself, since the Myo2 vesicle transporter did not show a decreased expression. Moreover,we did not observe either a deficiency in the number of actin cables at large cell volumes, indicating that the actin-based transport system was not limiting. For all these reasons, we concluded that the problem could reside in the vesicle contents, the cargo. Therefore, we studied representative proteins needed for active growth in the Gl/S transition and found that their cell concentration was reduced at large volumes. As a central set of experiments of this work, we compared the transcriptomes of small and large cells while performing the Gl/S transition, and found many genes belonging to specific functional categories that were upregulated or downregulated in large cells compared to small cells.Among those we found genes related to apical growth, vesicle transport, cytoskeleton, but especially to ribosomal biogenesis, which represents an extraordinary energetic cost, and must be extremely well regulated for optimal growth. Finally, for paradigmatic genes in these categories, we performed a careful analysis of gene insufficiency and confirmed their limiting effects on bud growth. In all, our results demonstrate that S.cerevisiae has established a critical size to achieve an optimal bud growth. At unusually larger sizes,the expression of ribosomal protein-related genes, as well as essential components for apical growth, is clearly reduced and, as a consequence,results in serious cell growth limitation

La degradació d'una proteïna d'andamiatge està relacionada amb la disminució dels receptors glutamatèrgics AMPA sinàptics

En un estudi publicat a la revista eNeuro, hem demostrat la importància de la degradació de la proteïna d'andamiatge AKAP150 a la regulació dels receptors de glutamat tipus AMPA, que estan associats a la plasticitat sinàptica. Aquesta investigació permetrà conèixer millor aquesta proteïna i obre la possibilitat de fer-la servir com a diana terapèutica en patologies del cervell que mostren una desregulació dels receptors AMPA sinàptics.En un estudio publicado en la revista eNeuro, hemos demostrado la importancia de la degradación de la proteína de andamiaje AKAP150 en la regulación de los receptores de glutamato tipo AMPA asociada a la plasticidad sináptica. Esta investigación permitirá conocer mejor esta proteína y abre la posibilidad de usarla como diana terapéutica en patologías del cerebro que muestran una desregulación de los receptores AMPA sinápticos.In our last publication, in eNeuro journal, we demonstrated the importance of the scaffold protein AKAP150 degradation in the regulation of AMPA-glutamate receptors associated with synaptic plasticity. This research will allow knowing better this protein and opening the possibility to use it as a therapeutic target in brain pathologies that present deregulation in synaptic AMPA receptors

MicroRNAs as Early Biomarkers of Alzheimer's Disease : a synaptic perspective

Aquest projecte ha rebut un ajut de la Fundació La Marató de TV3, ref. TV3-2014-3610.Pathogenic processes underlying Alzheimer's disease (AD) affect synaptic function from initial asymptomatic stages, long time before the onset of cognitive decline and neurodegeneration. Therefore, reliable biomarkers enabling early AD diagnosis and prognosis are needed to maximize the time window for therapeutic interventions. MicroRNAs (miRNAs) have recently emerged as promising cost-effective and non-invasive biomarkers for AD, since they can be readily detected in different biofluids, including cerebrospinal fluid (CSF) and blood. Moreover, a growing body of evidence indicates that miRNAs regulate synaptic homeostasis and plasticity processes, suggesting that they may be involved in early synaptic dysfunction during AD. Here, we review the current literature supporting a role of miRNAs during early synaptic deficits in AD, including recent studies evaluating their potential as AD biomarkers. Besides targeting genes related to Aβ and tau metabolism, several miRNAs also regulate synaptic-related proteins and transcription factors implicated in early synaptic deficits during AD. Furthermore, individual miRNAs and molecular signatures have been found to distinguish between prodromal AD and healthy controls. Overall, these studies highlight the relevance of considering synaptic-related miRNAs as potential biomarkers of early AD stages. However, further validation studies in large cohorts, including longitudinal studies, as well as implementation of standardized protocols, are needed to establish miRNA-based biomarkers as reliable diagnostic and prognostic tools

Un estudio sobre el análisis económico-financiero de las empresas sociales: ¿son realmente negocios?

The main objective of this research paper is to analyze the economic and financial situation of social enterprises through ratio analysis and show their strengths and weaknesses based on financial data. The sample consists of 118 social companies operating in the Autonomous Community of Madrid in Spain. For data analysis, economic and financial analysis has been carried out, using ratio analysis and the indicator of financial distress: the Altman Z’-score. Our findings highlight that social companies are businesses with a high level of profitability, especially for their partners. Thus, their survival, on average, is guaranteed in the long-term and their liquidity level is optimum. This study is an important contribution for the academic literature, because it carries out a comparison amongst the two different types of social firms, focusing on their economic and financial structure, diminishing the lack of empirical studies about these companies.El principal objetivo de esta investigación es analizar la situación económico- financiera de las empresas sociales a través del análisis de ratios, mostrando sus fortalezas y debilidades basándonos en la información contable. La muestra está formada por 118 empresas sociales situadas en la Comunidad Autónoma de Madrid en España. Para analizar los datos se han utilizado ratios económico-financieros y el indicador de estrés financiero, el Z’-score de Altman . Nuestros resultados destacan que las empresas sociales son negocios con una elevada rentabilidad, especialmente para sus socios. De este modo, está garantizada su supervivencia en el largo plazo y con un nivel de liquidez óptimo. Este estudio es una importante contribución para la literatura académica porque establece una comparación entre dos tipos de negocios sociales centrándonos en su estructura financiera y económica, completando la escasez de estudios empíricos sobre estas empresas.Depto. de Administración Financiera y ContabilidadFac. de Ciencias Económicas y EmpresarialesTRUEpu

The profitability of socially responsible companies: Public subsidies for sheltered employment centers

During economic crises, more than ever, the companies realize the impact of their activities on society through their social reponsibility. Firms that practice social responsibility strategies are more attractive to their customers, and sometimes this is a way to obtain competitive advantages such as creation of value, better social image, high consumer loyalty and, in consequence, higher profits. Prior literature justifies that there is a positive association between corporate social responsibility and financial performance. A kind of company with a special commitment to develop its business in a responsible way for society is sheltered employment centers, businesses whose workers are mostly disabled people. The objective of this paper is to analyse whether the sheltered employment centers that receive public subsidies achieve greater economic profitability on average than those centers that do not receive it. Although the number of these firms has been growing during the crisis, when governments have reduced their financial help, some theoretical papers justify their profitability due to public subsidies received. After obtaining the total sample of sheltered employment centers in the Community of Madrid using statistical and artificial intelligence methods, our results show that sheltered employment centers, on average, are productive enterprises in which their profitability is not conditioned by the public aid granted. The model obtained shows that these companies are profitable businesses when they can pay their interest expenses with profits every period. Additionally, the social and labour integration of disabled people is a way to improve their corporate social responsibility

Risk factor selection in automobile insurance policies: a way to improve the bottom line of insurance companies

The objective of this paper is to test the validity of using 'bonus-malus' (BM) levels to classify policyholders satisfactorily. In order to achieve the proposed objective and to show empirical evidence, an artificial intelligence method, Rough Set theory, has been employed. The empirical evidence shows that common risk factors employed by insurance companies are good explanatory variables for classifying car policyholders' policies. In addition, the BM level variable slightly increases the explanatory power of the a priori risks factors

Analysis of corporate viability in the pre-bankruptcy proceedings

Companies in financial difficulties can avail themselves of the pre-bankruptcy procedure, prior to its entry in the legal process of insolvency. The objective of this paper is to look for a possible diagnosis of some common distressed firm’s characteristics in order to be successful at pre-bankruptcy procedure through artificial intelligence methodologies. Using a Spanish sample of bankrupt and healthy firms, our results show that financial viability and working capital ratios are fundamental for the effectiveness of pre-bankruptcy legal procedure. These findings may help to shed light on the implications for all the stakeholders involved in a pre-bankruptcy procedure

Money laundering and terrorism financing detection using neural networks and an abnormality indicator

This study proposes a comprehensive model that helps improve self-comparisons and group-comparisons for customers to detect suspicious transactions related to money laundering (ML) and terrorism financing (FT) in financial systems. The self-comparison is improved by establishing a more comprehensive know your customer (KYC) policy, adding non-transactional characteristics to obtain a set of variables that can be classified into four categories: inherent, product, transactional, and geographic. The group-comparison involving the clustering process is improved by using an innovative transaction abnormality indicator, based on the variance of the variables. To illustrate the way this methodology works, random samples were extracted from the data warehouse of an important financial institution in Mexico. To train the algorithms, 26,751 and 3527 transactions and their features, involving natural and legal persons, respectively, were selected randomly from January 2020. To measure the prediction accuracy, test sets of 1000 and 600 transactions were selected randomly for natural and legal persons, respectively, from February 2020. The proposed model manages to decrease the proportion of false positives and increase accuracy when compared to the rule-based system. On reducing the false positive rate, the company’s costs for investigating suspicious customers also decrease significantly

Social Entrepreneurship in Sheltered Employment Centres: A Case Study of Business Success

Sheltered Employment centres (CEEs) are part of the social economy companies, based on the primacy of people over capital, social benefits and solidarity. Its aim is to carry out productive work and they are a means of integration of the greatest possible number of disabled people. There is a growing interest in this type of business because its number has increased considerably. The objective of this chapter is to give academic visibility to CEEs due to its great contribution to the social corporate responsibility and to encourage the so-called social entrepreneurship. The reasons for creating social firms are analysed and the characteristics that can contribute to the success of this type of companies are studied. Using the case study methodology, a CEE is analysed in depth showing the main features of social economy business by means of a specific case and the key variables that has conducted to its success

Detection of shell companies in financial institutions using dynamic social network

Shell companies work in financial interaction with other companies to commit several crimes such as concealing resources of illicit origin (money laundering), tax fraud (tax evasion), corruption, bribery, and drug trafficking, among others. This interaction can be represented by a set of nodes and connections that show the multiple relationships between entities over time. The current article proposes to detect transactions related to shell companies in financial systems, using legal person attributes and incorporating self and group comparisons into dynamic social networks. The months of June 2019, September 2020, and November 2021 are taken as evaluation periods to test the proposed methodology. Our methodology performs better than the traditional rules method, yielding balanced accuracies and true positive rates above 0.9 and 0.85, respectively. The false-positive rate was also lower in the proposed model than in the rule system for most evaluation periods. The latter translates into a reduction in costs by compliance investigations