Catching transcriptional regulation by thermostatistical modeling

Gene expression is frequently regulated by multiple transcription factors (TFs). Thermostatistical methods allow for a quantitative description of interactions between TFs, RNA polymerase and DNA, and their impact on the transcription rates. We illustrate three different scales of the thermostatistical approach: the microscale of TF molecules, the mesoscale of promoter energy levels and the macroscale of transcriptionally active and inactive cells in a cell population. We demonstrate versatility of combinatorial transcriptional activation by exemplifying logic functions, such as AND and OR gates. We discuss a metric for cell-to-cell transcriptional activation variability known as Fermi entropy. Suitability of thermostatistical modeling is illustrated by describing the experimental data on transcriptional induction of NF?B and the c-Fos protein.

Study of Rgmc regulation by iron levels, anemia, inflammation and hypoxia

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Study of Rgmc regulation by iron levels, anemia, inflammation and hypoxia

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

The Pocket Statistician: A Practical Guide to Quality Improvement by Shirley Coleman, Tony Greenfield, Roger Jones, Clare Morris and Ian Puzey. Arnold . 1996. 252 pages. £12.99 [Book review]

Abstract not available

Post-translational lysine-acetylation of Ran and its regulation by Sirtuin deacetylases

Through recent advances in high-throughput mass spectrometry it has become evident that post-translational N-(epsilon)-lysine-acetylation is a modification found on thousands of proteins of all cellular compartments and all essential physiological processes. Many aspects in the biology of lysine-acetylation are poorly understood, including its regulation by lysine-acetyltransferases and lysine-deacetylases (KDACs). Here, the role of this modification was investigated for the small GTP-binding protein Ran, which, inter alia, is essential for the regulation of nucleocytoplasmic transport. To this end, site-specifically acetylated Ran was produced in E. coli by genetic code expansion. For five previously identified sites, Ran acetylation was tested regarding its impact on the intrinsic GTP hydrolysis rate, the assembly of export complexes (modeled in vitro with the export receptor CRM1 and the export substrate Spn1) and the interaction of Ran with its GTPase activation protein RanGAP and RanBP1. Overall, mild effects of Ran acetylation were observed for intrinsic and RanGAP-stimulated GTP hydrolysis rates. The interaction of active Ran with RanBP1 was negatively influenced by Ran acetylation at K159. Moreover, CRM1 bound to Ran acetylated at K37, K99 or K159 interacted more strongly with Spn1. Thus, lysine-acetylation interferes with essential aspects of Ran function. An in vitro screen was performed to identify potential Ran KDACs. The NAD+-dependent KDACs of the Sirtuin class showed activity towards two acetylation sites of Ran, K37 and K71. The specificity of Sirtuins was further analyzed based on an additional Ran acetylation site, K38. Since deacetylation of RanAcK38 was much slower compared to RanAcK37, di-acetylated RanAcK37/38 was tested next. The deacetylation rate of di-acetylated Ran was comparable to that of RanAcK37. Deacetylation experiments under single turnover conditions revealed that deacetylation occurs first at the K38 site in the di-acetylated RanAcK37/38 background. The ability of Sirtuins to deacetylate two adjacent AcKs was further investigated based on two proteins, which had previously been found to be di-acetylated and targeted by Sirtuins, namely the tumor suppressor protein p53 and phosphoenolpyruvate carboxykinase 1 (PEPCK1). p53 was readily deacetylated at two di-acetylation sites (K372/372 and K381/382), whereas PEPCK1 was not deacetylated in vitro. Taken together, these results have important implications for the substrate specificity of Sirtuins.

Effects of light quality supplied by light emitting diodes (LEDs) on microalgal production

Dissertação de mestrado, Aquacultura, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

An industry viewpoint on the role of farm assurance in delivering food safety to the consumer: the case of the dairy sector in England and Wales

Food safety, alongside food quality, remains a primary concern of both consumers and those along the whole food supply chain, leading to regulation by government alongside private third party certification. Much has been written about the value of these systems primarily from the perception of the consumer. This paper reports on a study that examined industry perceptions on the regulatory and assurance systems within the dairy sector of England and Wales. It found that the primary producer found value in both systems, although from a food hygiene focus regulation was seen to be more rigorous. Other stakeholders along the dairy food supply chain saw the assurance scheme as more rigorous. All stakeholders recognised the need to reduce duplication in delivering food safety through combining key elements of both systems with the added potential for better communication of both food safety and quality to the final consumer.

Relations between regulation, competition policy and consumer protection in telecommunications, electricity and water supply

The purpose of this article is to discuss the relations between regulation, competition policy and consumer protection these relations in three key sectors of Brazil’s infrastructure: telecommunications, electricity and water supply. A study of the literature points to two general principles. First, the need for consumer protection depends on the “degree of sovereignty” enjoyed by consumers, defined in terms of the cost of consumer organization, consumers’ ability to evaluate services, and the level of competition in each sector. Second, the less sovereignty consumers enjoy the more consumer protection institutions are involved with regulation agencies. The evidence for the Brazilian case apparently corroborates these points. In addition, it is important to stress that consumer complaints in regulated sectors seem to have increased more intensely than in others. The article is divided into three sections. Section 1 presents theoretical elements and aspects of the relations between regulation, competition policy and consumer protection evidenced by international experience. Section 2 analyzes the Brazilian experience and in particular the available statistics on consumer complaints about telecommunications, electricity and water supply, submitted to Fundação Procon-SP during the nineties. The last section points to possible configurations of the institutional relations between competition policy, regulation and consumer protection, showing how the existing configuration of these areas in the three infrastructure sectors discussed confirms that the theoretical framework proposed has reasonable predictive power.

Proteasomal degradation of N-acetyltransferase 1 is prevented by acetylation of the active site cysteine - A mechanism for the slow acetylator phenotype and substrate-dependent down-regulation

Many drugs and chemicals found in the environment are either detoxified by N-acetyltransferase 1 (NAT1, EC 2.3.1.5) and eliminated from the body or bioactivated to metabolites that have the potential to cause toxicity and/or cancer. NAT1 activity in the body is regulated by genetic polymorphisms as well as environmental factors such as substrate-dependent down-regulation and oxidative stress. Here we report the molecular mechanism for the low protein expression from mutant NAT1 alleles that gives rise to the slow acetylator phenotype and show that a similar process accounts for enzyme down-regulation by NAT1 substrates. NAT1 allozymes NAT1 14, NAT1 15, NAT1 17, and NAT1 22 are devoid of enzyme activity and have short intracellular half-lives (similar to4 h) compared with wild-type NAT1 4 and the active allozyme NAT1 24. The inactive allozymes are unable to be acetylated by cofactor, resulting in ubiquitination and rapid degradation by the 26 S proteasome. This was confirmed by site-directed mutagenesis of the active site cysteine 68. The NAT1 substrate p-aminobenzoic acid induced ubiquitination of the usually stable NAT1 4, leading to its rapid degradation. From this study, we conclude that NAT1 exists in the cell in either a stable acetylated state or an unstable non-acetylated state and that mutations in the NAT1 gene that prevent protein acetylation produce a slow acetylator phenotype.

Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow

IL-13 and eotaxin play important, inter-related roles in asthma models. In the lungs, CysLT, produced by the 5-LO-LTC4S pathway, mediate some local responses to IL-13 and eotaxin; in bone marrow, CysLT enhance IL-5-dependent eosinophil differentiation. We examined the effects of IL-13 and eotaxin on eosinophil differentiation. Semi-solid or liquid cultures were established from murine bone marrow with GM-CSF or IL-5, respectively, and the effects of IL-13, eotaxin, or CysLT on eosinophil colony formation and on eosinophil differentiation in liquid culture were evaluated, in the absence or presence of: a) the 5-LO inhibitor zileuton, the FLAP inhibitor MK886, or the CysLT1R antagonists, montelukast and MK571; b) mutations that inactivate 5-LO, LTC4S, or CysLT1R; and c) neutralizing mAb against eotaxin and its CCR3 receptor. Both cytokines enhanced GM-CSF-dependent eosinophil colony formation and IL-5-stimulated eosinophil differentiation. Although IL-13 did not induce eotaxin production, its effects were abolished by anti-eotaxin and anti-CCR3 antibodies, suggesting up-regulation by IL-13 of responses to endogenous eotaxin. Anti-CCR3 blocked eotaxin completely. The effects of both cytokines were prevented by zileuton, MK886, montelukast, and MK571, as well as by inactivation of the genes coding for 5-LO, LTC4S, and CysLT1R. In the absence of either cytokine, these treatments or mutations had no effect. These findings provide evidence for: a) a novel role of eotaxin and IL-13 in regulating eosinophilopoiesis; and b) a role for CysLTRs in bone marrow cells in transducing cytokine regulatory signals. J. Leukoc. Biol. 87: 885-893; 2010.

Análise da Qualidade de Energia em Instalações Eléctricas com MiniProdução

Com a alteração da legislação energética em Portugal, nomeadamente a implementação da legislação de Micro e Minigeração, a produção distribuída cresceu de forma exponencial na rede elétrica nacional, diminuindo por um lado as perdas no transporte e distribuição, e por outro aumentando a complexidade na gestão do trânsito de potência ao Distribuidor. No entanto a motivação desta dissertação prende-se com o facto de que as centrais de produção distribuída, em particular as de tecnologia fotovoltaica, pela sua dimensão, serem instaladas nos pontos de consumo, em paralelo com a instalação elétrica de utilização do cliente e como tal, têm sido verificadas diversas anomalias no funcionamento e exploração das mesmas, por influência da má qualidade de energia resultante das más condições de funcionamento e exploração em que se encontram as instalações de consumo. A presente dissertação pretende apresentar uma descrição das anomalias mais frequentes verificadas nas centrais fotovoltaicas de minigeração com origem na qualidade da energia que transita das instalações elétricas de consumo ligadas ao mesmo ponto de interligação com a rede elétrica nacional. Como base de fundamento, foram demonstradas através de três casos práticos reais, algumas das mais frequentes e prejudiciais anomalias descritas na presente dissertação. Foram escolhidos 3 casos reais com diferentes tipos de instalação de consumo sendo que um deles não apresenta qualquer anomalia de forma a comprovar o bom funcionamento em condições normais de ambas as instalações. Foram encontradas e demonstradas várias soluções paras os diferentes tipos de anomalias, no entanto esta dissertação vai permitir não só a resolução deste tipo de anomalias em centrais fotovoltaicas em exploração e já com prejuízos avultados mas também introduzir em futuras instalações a análise da qualidade da energia nas instalações de consumo em fase preliminar de estudo de implementação de centrais fotovoltaicas de minigeração e de autoconsumo, precavendo futuros problemas de rentabilidade técnico-económica. Este estudo, irá certamente servir de motor de impulsão para a preocupação com a Qualidade da Energia essencialmente dentro das instalações elétricas de consumo sensibilizando os seus gestores energéticos. Poderá ainda impulsionar a reformulação do Regulamento de Qualidade de Serviço para exigências ainda mais apertadas de forma a incorporar algumas das anomalias aqui descritas, sendo por isso um elemento de alerta para todos os “Players” do Sistema Elétrico Nacional tendo como limite a melhoria continua da Segurança e da Qualidade da energia na rede elétrica beneficiando da sensibilização de todos os intervenientes.