Search

Nicotinamide‐adenine dinucleotide (NAD) is involved in redox homeostasis and acts as a substrate for NADases, including poly(ADP‐ribose) polymerases (PARPs) that add poly(ADP‐ribose) polymers to proteins and DNA, and sirtuins that deacetylate proteins. Nicotinamide, a by‐product of NADases increases circadian period in both plants and animals. In mammals, the effect of nicotinamide on circadian period might be mediated by the PARPs and sirtuins because they directly bind to core circadian oscillator genes. We have investigated whether PARPs and sirtuins contribute to the regulation of the circadian oscillator in Arabidopsis. We found no evidence that PARPs and sirtuins regulate the circadian oscillator of Arabidopsis or are involved in the response to nicotinamide. RNA‐seq analysis indicated that PARPs regulate the expression of only a few genes, including FLOWERING LOCUS C. However, we found profound effects of reduced sirtuin 1 expression on gene expression during the day but not at night, and an embryo lethal phenotype in knockouts. Our results demonstrate that PARPs and sirtuins are not associated with NAD regulation of the circadian oscillator and that sirtuin 1 is associated with daytime regulation of gene expression.

Frameshift mutations in CALR (calreticulin) are associated with essential thrombocythaemia (ET), but the stages at and mechanisms by which mutant CALR drives transformation remain incompletely defined. Here, we use single-cell approaches to examine the haematopoietic stem/progenitor cell (HSPC) landscape in a mouse model of mutant CALR-driven ET. We identify a trajectory linking HSCs with megakaryocytes and prospectively identify a novel intermediate population that is overrepresented in the disease state. We also show that mutant CALR drives transformation primarily from the earliest stem cell compartment, with some contribution from megakaryocyte progenitors. Finally, relative to wild-type HSCs, mutant CALR HSCs show increases in JAK-STAT signalling, the unfolded protein response, cell cycle, and a previously undescribed upregulation of cholesterol biosynthesis. Overall, we have identified a novel megakaryocyte-biased cell population that is increased in a mouse model of ET and described transcriptomic changes linking CALR mutations to increased HSC proliferation and megakaryopoiesis., Work in the Göttgens lab is supported by the Medical Research Council (MR/M008975/1), Wellcome (206328/Z/17/Z), Blood Cancer UK (18002), and Cancer Research UK (RG83389, jointly with A.R.G). Work in the Green lab is supported by Wellcome (RG74909), WBH Foundation (RG91681), and Cancer Research UK (RG83389, jointly with B.G.).

Nicotinamide-adenine dinucleotide (NAD) is involved in redox homeostasis and acts as a substrate for NADases, including poly(ADP-ribose) polymerases (PARPs) that add poly(ADP-ribose) polymers to proteins and DNA, and sirtuins that deacetylate proteins. Nicotinamide, a by-product of NADases increases circadian period in both plants and animals. In mammals, the effect of nicotinamide on circadian period might be mediated by the PARPs and sirtuins because they directly bind to core circadian oscillator genes. We have investigated whether PARPs and sirtuins contribute to the regulation of the circadian oscillator in Arabidopsis. We found no evidence that PARPs and sirtuins regulate the circadian oscillator of Arabidopsis or are involved in the response to nicotinamide. RNA-seq analysis indicated that PARPs regulate the expression of only a few genes, including FLOWERING LOCUS C. However, we found profound effects of reduced sirtuin 1 expression on gene expression during the day but not at night, and an embryo lethal phenotype in knockouts. Our results demonstrate that PARPs and sirtuins are not associated with NAD regulation of the circadian oscillator and that sirtuin 1 is associated with daytime regulation of gene expression.

Os mercados empresariais deixaram de ser locais, regionais ou nacionais, para passarem a ser internacionais. A globalização passou a ser um fator critico de sucesso, com as empresas, especialmente as Pequenas e Médias Empresas, a terem que adequar a sua estrutura empresarial de forma a poderem responder às diferentes necessidades dos seus clientes nacionais e internacionais e à crescente agressividade e competitividade empresarial. A adoção de um plano de marketing internacional, surge então como uma ferramenta fundamental para apoiar as empresas no processo de internacionalização. Neste sentido, o presente estudo tem como objetivo principal a escolha de um modelo de plano de marketing internacional para as Pequenas e Médias Empresas portuguesas. Para esse efeito, procedemos a uma extensa revisão bibliográfica de trabalhos que abordavam o tema, tendo escolhido três estudos que nos pareciam mais adequados e procedido à sua análise detalhada. No final escolhemos um plano de marketing internacional, adequado às especificidades das Pequenas e Médias Empresas portuguesas, que apresentava caraterísticas de simplicidade de compreensão e implementação, diversidade e complementaridade dos temas abordados e dava especial relevância ao fator de implementação e controlo. info:eu-repo/semantics/publishedVersion

Relatório de Estágio - Mestrado em Ensino da Música Submitted by Luísa Marques (lmarques@esml.ipl.pt) on 2018-01-22T16:49:51Z No. of bitstreams: 1 mestrado_hugo_bastos.pdf: 1526601 bytes, checksum: 33e8c8a4cee53f21a5da7041cb6de1db (MD5) Made available in DSpace on 2018-01-22T16:49:51Z (GMT). No. of bitstreams: 1 mestrado_hugo_bastos.pdf: 1526601 bytes, checksum: 33e8c8a4cee53f21a5da7041cb6de1db (MD5) Previous issue date: 2017-04 N/A

Objectives:Describe a clinical case of a 23 years old patient diagnosed with type I diabetes (T1D) and several hospitalizations due to self-induced diabetic ketoacidosis.Background:Self-injury is described as the deliberate destruction of body tissue without suicidal intention, usually with different purposes. Itu2019s more frequent among adolescents and young adults and can have several forms. It has already been described that individuals who are diagnosed with T1D are at greater risk of self-harm behaviors, usually inducing hypoglycemia resulting from their easy access to insulin.Materials and Methods:Clinical case description and literature review about self-harm behavior among T1D patients.Results and Conclusions:We present a case of a 23 years old man, diagnosed with T1D. From 2015 to February 2019 he was admitted to the hospital twenty times due to diabetic ketoacidosis. During one of his admissions, was observed by Psychiatry suspecting that these episodes were due to lack of adherence to treatment. He kept regular follow-up at Psychiatry appointments and we were able to realize the presence of familiar adversities that triggered deliberate episodes of binge carbohydrates ingestion and pharmacologic misuse leading to glycemic decompensation and consequent admissions to the hospital. With this clinical case report, we try to highlight the important relationship between chronic diseases and the presence of self-injury behavior, especially among adolescents and young adults. Sometimes, this kind of aggression can have atypical presentations, like the one described above, reinforcing the importance of a detailed clinical history and a close follow-up, in order to stabilize these patients and optimize their care.

Objectives:Describe a Kleine-Levin Syndrome (KLS) and discuss its clinical presentation, diagnostic criteria and therapeutic approach. Background:KLS is described as a rare disorder presenting with recurrent episodes of unexplained hypersomnia lasting from few days to several weeks, hyperphagia and hypersexuality. It affects mainly young male individuals. Between episodes, subjects donu2019t show any symptom and sometimes describe retrograde amnesia for their behavior. Nevertheless, and since this disorder can cause a great impairment on social and working abilities during episodes, we can observe a significant prevalence of depression and anxiety among patients as a consequence of their clinical situation.Materials and Methods:Clinical case description and literature review about KLS.Results and Conclusions:We present the case of a 51 years old male that was assisted at the Neurology emergency room (ER) from Centro Hospitalar de Tru00e1s-os-Montes e Alto Douro presenting disorientation, sexual impulsivity, aggressiveness, hypersomnia and hyperfagia. He was already being followed at Psychiatry appointments and medicated with valproic acid. At the ER, the only change detected was a level of valproic acid below therapeutic cut-off. He was then admitted at Psychiatric ward in order to optimize medication and stabilize symptoms.Despite being rare, KLS can lead to great changes on personal, social and working life of our patients. Besides, this condition can be related to the emergence of depressive and anxious symptoms that must be adequately treated. For all these reasons, itu2019s important to approach this theme in order to raise awareness of its existence and improve its diagnosis and treatment.

Tese de doutoramento, Informática (Bioinformática), Universidade de Lisboa, Faculdade de Ciências, 2015 Submitted by Amelia Janeiro (ajaneiro@reitoria.ul.pt) on 2015-08-07T13:47:02Z No. of bitstreams: 1 ulsd071075_td_Hugo_Bastos.pdf: 4993562 bytes, checksum: cc83b25726acf1af94414854a994e6ba (MD5) Made available in DSpace on 2015-08-12T10:08:15Z (GMT). No. of bitstreams: 1 ulsd071075_td_Hugo_Bastos.pdf: 4993562 bytes, checksum: cc83b25726acf1af94414854a994e6ba (MD5) Previous issue date: 2015 Fundação para a Ciência e a Tecnologia (FCT), SFRH/BD/48035/2008

Bibliografia: p. 288-290 O vidro plano é um componente importante das cadeias de produção tanto da construção civil quanto da indústria automobilística e vem se destacando com a apresentação de diversas características e funcionalidades. A indústria de vidro plano é concentrada em nível mundial, situação também observada nacionalmente. Contudo, no Brasil, essa indústria tem passado por importantes transformações em sua estrutura, com a entrada de novos participantes. Esse movimento reflete o comportamento da demanda interna e de seus principais indutores de crescimento. Este artigo se propõe a apresentar a conjuntura atual desse mercado, em um ambiente de transformação e expansão, e apontar suas perspectivas, levando em conta a importância do desenvolvimento nacional dessa indústria tanto para as cadeias de produção das quais faz parte quanto para o equilíbrio da balança comercial.