Modelo de policiamento na GNR : Experiência do Destacamento Territorial de Coimbra

O Policiamento de Proximidade é o modelo de policiamento atual em Portugal, privilegiando uma postura preventiva e dando relevo à pró-atividade das forças policiais. À Guarda Nacional Republicana, enquanto força policial, cabe-lhe zelar pelos direitos, liberdades e garantias dos cidadãos, constitucionalmente protegidos, através dessa atuação preventiva, procurando intensificar pró-ativamente a sua presença no seio da sociedade. Contudo, por vezes é necessário recorrer a uma intervenção de caráter repressivo, a fim de repor a ordem e visando uma prevenção futura, evitando os comportamentos antissociais. Torna-se assim pertinente estudar de que forma se articulam a atuação preventiva e repressiva da GNR, de modo a perceber se é possível existir um equilíbrio entre elas, ou se, por alguma razão, existem limitações no seu emprego. O Destacamento Territorial de Coimbra constitui o estudo de caso. Esta investigação para além de descrever a articulação entre ambas as formas de atuação, pretende ainda identificar aquilo que as caracteriza bem como as suas potencialidades e vulnerabilidades. De forma a recolher a informação pretendida, foram privilegiadas a análise documental, entrevistas ao Comandante de Destacamento Territorial de Coimbra e aos respetivos Comandantes dos Postos Territoriais, bem como questionários aos militares do destacamento responsáveis por exercerem o patrulhamento. Seguidamente procedeu-se à análise de conteúdo dos dados recolhidos. Das conclusões retiradas, salienta-se que a falta de recursos principalmente humanos, corresponde a um problema do destacamento, que dificulta uma ação de patrulhamento contínuo junto do cidadão e que contribui para o Policiamento de Proximidade. Denota-se também a intensa fiscalização rodoviária que, apesar de ter uma natureza preventiva, é interpretada pela população com uma imagem de repressão.

Geminivirus Rep Protein Interferes with the Plant DNA Methylation Machinery and Modifies the Host Epigenome

The apparent simplicity of viruses hides the complexity of their interactions with their hosts. Viruses are masters at circumventing host defenses and manipulating the cellular environment for their own benefit. The replication of the largest known family of single-stranded DNA viruses, Geminiviridae, is impaired by DNA methylation and Arabidopsis mutants affected in cytosine methylation are hypersusceptible to geminivirus infection. This implies that plants might use methylation as a defense against geminiviruses and that the viral genome is a target for plant DNA methyltransferases. We have found a novel counter-defense strategy used by geminiviruses, that reduces the expression of the plant maintenance DNA methyltransferases, MET1 and CMT3, in both, locally and systemically infected tissues. Furthermore, we demonstrated that the virus-mediated repression of these two maintenance DNA methyltransferases is widely spread among different geminivirus species. Additionally, we identified Rep as the geminiviral protein responsible for the repression of MET1 and CMT3, and another viral protein, C4, as an ancillary player in MET1 downregulation. The presence of Rep, suppresses TGS of an Arabidopsis transgene and of host loci whose expression is strongly controlled by CG methylation. Bisulfite sequencing analyses showed that the expression of Rep caused a substantial reduction in the levels of DNA methylation at CG sites. Our findings suggest that Rep, the only viral protein essential for geminiviral replication, displays TGS suppressor activity through a mechanism distinct from the one thus far described for geminiviruses.

Community‐based reconciliation in the Middle East

IntroductionWith the turn of the twenty first century, the Middle East has witnessed an unprecedented turmoil since the post‐colonisation era. The occupation of Iraq by the United States and its allies has triggered internal tensions and violence in Iraq that swept across the region. The US propagated establishing a pro‐western, functional, representative democratic system in Iraq that was expected to be a model for other countries in the region towards democratisation and economic growth. Since 2011, Some Arab states embraced democratic and political changes and, simultaneously, encountered some socio‐political unrest brought by the “Arab Spring”. Various strata of conflict can be recognised in this context driven by political, ideological and sectarian agenda; or, driven by mere struggle for freedom and against repression and dictatorship. Regardless of the trigger of strives, it is obvious that reconciliation and conflict management in Iraq, Syria, Libya, Yemen, Egypt and other countries in conflict is still an issue. Yet, the concept of community‐based reconciliation in the Arab World is still nuanced. The social ties in Arab societies are strong. Some of these ties are significantly noted to be recognised in kinship of various familial hierarchies: nucleus family, extended family and tribes. This paper will discuss whether familial affiliations can contribute to community‐based reconciliation in the Middle Eastern Arab countries.

Exercise, skeletal muscle and circulating microRNAs

Regular exercise stimulates numerous structural, metabolic, and morphological adaptations in skeletal muscle. These adaptations are vital to maintain human health over the life span. Exercise is therefore seen as a primary intervention to reduce the risk of chronic disease. Advances in molecular biology, biochemistry, and bioinformatics, combined with exercise physiology, have identified many key signaling pathways as well as transcriptional and translational processes responsible for exercise-induced adaptations. Noncoding RNAs, and specifically microRNAs (miRNAs), constitute a new regulatory component that may play a role in these adaptations. The short single-stranded miRNA sequences bind to the 3' untranslated region of specific messenger RNAs (mRNAs) on the basis of sequence homology. This results in the degradation of the target mRNA or the inhibition of protein translation causing repression of the corresponding protein. While tissue specificity or enrichment of certain miRNAs makes them ideal targets to manipulate and understand tissue development, function, health, and disease, other miRNAs are ubiquitously expressed; however, it is uncertain whether their mRNA/protein targets are conserved across different tissues. miRNAs are stable in plasma and serum and their altered circulating expression levels in disease conditions may provide important biomarker information. The emerging research into the role that miRNAs play in exercise-induced adaptations has predominantly focused on the miRNA species that are regulated in skeletal muscle or in circulation. This chapter provides an overview of these current research findings, highlights the strengths and weaknesses identified to date, and suggests where the exercise-miRNA field may move into the future.

Disruption of the class IIa HDAC corepressor complex increases energy expenditure and lipid oxidation

Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase) transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid oxidation. An existing HDAC inhibitor, Scriptaid, had similar phenotypic effects through disruption of the class IIa HDAC corepressor complex. Acute Scriptaid administration to mice increased the expression of metabolic genes, which required an intact class IIa HDAC corepressor complex. Chronic Scriptaid administration increased exercise capacity, whole-body energy expenditure and lipid oxidation, and reduced fasting blood lipids and glucose. Therefore, compounds that disrupt class IIa HDAC function could be used to enhance metabolic health in chronic diseases driven by physical inactivity.

Fluoroquinolone efflux in Streptococcus suis is mediated by SatAB and not by SmrA

Streptococcus suis is an emerging zoonotic pathogen. With the lack of an effective vaccine, antibiotics remain the main tool to fight infections caused by this pathogen. We have previously observed a reserpine-sensitive fluoroquinolone (FQ) efflux phenotype in this species. Here, SatAB and SmrA, two pumps belonging to the ATP binding cassette (ABC) and the major facilitator superfamily (MFS), respectively, have been analyzed in the fluoroquinolone-resistant clinical isolate BB1013. Genes encoding these pumps were overexpressed either constitutively or in the presence of ciprofloxacin in this strain. These genes could not be cloned in plasmids in Escherichia coli despite strong expression repression. Finally, site-directed insertion of smrA and satAB in the amy locus of the Bacillus subtilis chromosome using ligated PCR amplicons allowed for the functional expression and study of both pumps. Results showed that SatAB is a narrow-spectrum fluoroquinolone exporter (norfloxacin and ciprofloxacin), susceptible to reserpine, whereas SmrA was not involved in fluoroquinolone resistance. Chromosomal integration in Bacillus is a novel method for studying efflux pumps from Gram-positive bacteria, which enabled us to demonstrate the possible role of SatAB, and not SmrA, in fluoroquinolone efflux in S. suis.

Aspectos cognitivos en torno a la novela y el cine de la memoria histórica: "La voz dormida" de Dulce Chacón y su adaptación fílmica

Culture, history, and biology are inseparable. Cultural manifestations are necessarily immersed in a context, originate in the embodied minds that create them, and are directed to the embodied minds that receive them and recreate them within their contexts (individual and collective). The novel and the film of historical memory in Spain aim to connect their audiences with a problem that has not been solved, as the Civil War, the postwar, and the pact of forgetfulness left a wide sector of the Spanish society voiceless. During the last few years, a series of initiatives coming from the arts, as well as other realms such as the legal, have sought to reexamine the unhealed wound that still haunts Spanish subjects. La voz dormida [The Sleeping Voice] is one of those initiatives. It begins as testimony, develops into a hybrid and intertextual novel, and later becomes a film. It constitutes an inclusive project, one of offering an alternative version to the “official history”, while incorporating the marginal voices of women that had been left out of the memory of the war and the dictatorship. Objective and Results By examining both the literary and the cinematic versions of Chacón’s work I aimed to evidence the connections that exist between the artistic portrayal of the postwar repression (particularly how it affects women) and the current movement of recovery of historical memory in Spain. Specifically, I was interested in showing how both the novel and the film employ a series of narrative strategies that emphasize the body and intentionality, with the purpose of creating in readers and spectators an empathetic response that may lead to prosocial behavior. In order to carry out this interdisciplinary study, which relates fiction, mind, and socio-historical context, I draw on cognitive theories of literature and film, as well as theories from social and developmental psychology, such as the Richard Gerrig’s theory of narrative experience, Keith Oatley’s psychology of fiction, Suzanne Keen’s theory of narrative empathy, and the empathy-altruism hypothesis, derived form the ideas of Jean Decety, among others...

Analysis of Transmission System Adequacy Considering the Constrained Fuzzy Power Flow

Power flow calculations are one of the most important tools for power system planning and operation. The need to account for uncertainties when performing power flow studies led, among others methods, to the development of the fuzzy power flow (FPF). This kind of models is especially interesting when a scarcity of information exists, which is a common situation in liberalized power systems (where generation and commercialization of electricity are market activities). In this framework, the symmetric/constrained fuzzy power flow (SFPF/CFPF) was proposed in order to avoid some of the problems of the original FPF model. The SFPF/CFPF models are suitable to quantify the adequacy of transmission network to satisfy “reasonable demands for the transmission of electricity” as defined, for instance, in the European Directive 2009/72/EC. In this work it is illustrated how the SFPF/CFPF may be used to evaluate the impact on the adequacy of a transmission system originated by specific investments on new network elements

Constrained fuzzy power flow models with correlation between nodal injections

This paper extends the symmetric/constrained fuzzy powerflow models by including the potential correlations between nodal injections. Therefore, the extension of the model allows the specification of fuzzy generation and load values and of potential correlations between nodal injections. The enhanced version of the symmetric/constrained fuzzy powerflow model is applied to the 30-bus IEEE test system. The results prove the importance of the inclusion of data correlations in the analysis of transmission system adequacy.

Probabilistic Security Constrained Fuzzy Power Flow Models

In restructured power systems, generation and commercialization activities became market activities, while transmission and distribution activities continue as regulated monopolies. As a result, the adequacy of transmission network should be evaluated independent of generation system. After introducing the constrained fuzzy power flow (CFPF) as a suitable tool to quantify the adequacy of transmission network to satisfy 'reasonable demands for the transmission of electricity' (as stated, for instance, at European Directive 2009/72/EC), the aim is now showing how this approach can be used in conjunction with probabilistic criteria in security analysis. In classical security analysis models of power systems are considered the composite system (generation plus transmission). The state of system components is usually modeled with probabilities and loads (and generation) are modeled by crisp numbers, probability distributions or fuzzy numbers. In the case of CFPF the component’s failure of the transmission network have been investigated. In this framework, probabilistic methods are used for failures modeling of the transmission system components and possibility models are used to deal with 'reasonable demands'. The enhanced version of the CFPF model is applied to an illustrative case.

Critical pedagogy theory and the family business

In contemporary times family business research has been dominated by three theoretical perspectives; principal-agent theory, stewardship theory, and resource-based view theory (Siebels 2012) but at the same time scholars argue that what still needs further attention is how underlying processes and phenomena can be explained (Melin, Nordqvist & Sharma  2014). In order to understand themes such as repression or relations of asymmetry the suggestion in this chapter is to move towards a critical stance of thinking which involves problematizing the obvious issues in family firms (Alvesson & Deetz 2000) and moreover allowing the critical perspective to destabilize assumptions made within earlier research (Freire, 1974). By discussing critical theory in general but foremost the Freirean  (1970, 1974) critical pedagogy specifically, the arguments in the chapter revolves around how critical pedagogy can open up for a more novel view on family business. The purpose is via critical pedagogy discuss family business from a limited situation perspective, and to argue for a Freirean (1970) dialogue as means of developing a critical consciousness for family members in the family business context. The chapter concludes with some recommendations on platforms or common grounds in which dialogue and raising of consciousness can occur in which the concept can open up possibilities for interesting learning transfer and bring multidimensional knowledge into the family firm.

Democracy and its aspiration in Hong Kong

This chapter addresses aspirations for more direct, representative democratic process in Hong, manifested in the street protests and occupations of 2014.

Caractérisation structurale de Miz-1 dans le cadre de la répression génique causée par le complexe c-Myc/Miz-1

Résumé : c-Myc est un facteur de transcription (FT) dont les niveaux cellulaires sont dérégulés dans la majorité des cancers chez l’homme. En hétérodimère avec son partenaire obligatoire Max, c-Myc lie préférentiellement les séquences E-Box (CACGTG) et cause l’expression de gènes impliqués dans la biosynthèse des protéines et des ARNs, dans le métabolisme et dans la prolifération cellulaire. Il est maintenant bien connu que c-Myc exerce aussi son potentiel mitogène en liant et inhibant différents FTs impliqués dans l’expression de gènes cytostatiques. Entre autres, c-Myc est en mesure d’inhiber Miz-1, un FT comportant 13 doigts de zinc de type Cys2-His2 (ZFs) impliqué dans l’expression de plusieurs gènes régulateurs du cycle cellulaire comprenant les inhibiteurs de CDK p15[indice supérieur INK4], p21[indice supérieur CIP1] et p57[indice supérieur KIP2]. Plus récemment, il fut démontré qu’en contrepartie, Miz-1 est aussi en mesure de renverser les fonctions activatrices de c-Myc et de prévenir la prolifération de cellules cancéreuses dépendantes de c-Myc. Ces différentes observations ont mené à la suggestion de l’hypothèse intéressante que la balance des niveaux de Miz-1 et c-Myc pourrait dicter le destin de la cellule et a permis d’établir Miz-1 comme nouvelle cible potentielle pour le développement d’agents anti-cancéreux. Malgré le fait que ces deux protéines semblent centrales à la régulation du cycle cellulaire, les mécanismes moléculaires leur permettant de s’inhiber mutuellement ainsi que les déterminants moléculaires permettant leur association spécifique demeurent assez peu documentés pour le moment. De plus, la biologie structurale de Miz-1 demeure à être explorée puisque qu’aucune structure de ses 13 ZFs, essentiels à sa liaison à l’ADN, n’a été déterminée pour l’instant. Les travaux réalisés dans le cadre cette thèse visent la caractérisation structurale et biophysique de Miz-1 dans le contexte de la répression génique causée par le complexe c-Myc/Miz-1. Nous présentons des résultats d’éxpériences in vitro démontrant que Miz-1 interagit avec c-Myc via un domaine contenu entre ses ZFs 12 et 13. De plus, nous démontrons que Miz-1 et Max sont en compétition pour la liaison de c-Myc. Ces résultats suggèrent pour la permière fois que Miz-1 inhibe les activités de c-Myc en prévenant son interaction avec son partenaire obligatoire Max. De plus, ils laissent présager que que Miz-1 pourrait servir de référence pour le développement d’inhibiteurs peptidiques de c-Myc. Finalement, nous avons réalisé la caractérisation structurale et dynamique des ZFs 1 à 4 et 8 à 10 de Miz-1 et avons évalué leur potentiel de liaison à l’ADN. Les résultats obtenus, couplés à des analyses bio-informatiques, nous permettent de suggérer un modèle détaillé pour la liaison spécifique de Miz-1 à son ADN consensus récemment identifié.

Élucidation et identification des différents interacteurs impliqués dans le mécanisme de régulation du LDLR par la protéine PCSK9

Résumé : Les maladies cardiovasculaires représentent la principale cause de mortalité mondiale, soit le tiers des décès annuels selon l’Organisation mondiale de la Santé. L’hypercholestérolémie, caractérisée par une élévation des niveaux plasmatiques de lipoprotéines de faible densité (LDL), est l’un des facteurs de risque majeur pour les maladies cardiovasculaires. La proprotéine convertase subtilisine/kexine type 9 (PCSK9) joue un rôle essentiel dans l’homéostasie du cholestérol sanguin par la régulation des niveaux protéiques du récepteur LDL (LDLR). PCSK9 est capable de se lier au LDLR et favorise l’internalisation et la dégradation du récepteur dans les lysosomes. L’inhibition de PCSK9 s’avère une cible thérapeutique validée pour le traitement de l’hypercholestérolémie et la prévention des maladies cardiovasculaires. Par contre, plusieurs mécanismes responsables de la régulation et la dégradation du complexe PCSK9-LDLR n’ont pas encore été complètement caractérisés comme la régulation par la protéine annexin A2 (AnxA2), un inhibiteur endogène de PCSK9. De plus, plusieurs évidences suggèrent la présence d’une ou plusieurs protéines, encore inconnues, impliquées dans le mécanisme d’action de PCSK9. Celles-ci pourraient réguler l’internalisation et le transport du complexe PCSK9-LDLR vers les lysosomes. Les objectifs de cette thèse sont de mieux définir le rôle et l’impact de l’AnxA2 sur la protéine PCSK9 en plus d’identifier de nouveaux partenaires d’interactions de PCSK9 pour mieux caractériser son mécanisme d’action sur la régulation des niveaux de LDLR. Nous avons démontré que l’inhibition de PCSK9 par l’AnxA2 extracellulaire s’effectue via sa liaison aux domaines M1+M2 de la région C-terminale de PCSK9 et nous avons mis en évidence les premières preuves d’un contrôle intracellulaire de l’AnxA2 sur la traduction de l’ARNm de PCSK9. Nos résultats révèlent une liaison de l’AnxA2 à l’ARN messager de PCSK9 qui cause une répression traductionnelle. Nous avons également identifié la protéine glypican-3 (GPC3) comme un nouveau partenaire d’interaction extracellulaire avec le PCSK9 et intracellulaire avec le complexe PCSK9-LDLR dans le réticulum endoplasmique des cellules HepG2 et Huh7. Nos études démontrent que GPC3 réduit l’activité extracellulaire de PCSK9 en agissant comme un compétiteur du LDLR pour la liaison avec PCSK9. Une meilleure compréhension des mécanismes de régulation et de dégradation du complexe PCKS9-LDLR permettra de mieux évaluer l’impact et l’efficacité des inhibiteurs de la protéine PCSK9.

Exploring the role of miR-34a in regulating adipose inflammation during obesity

Background: Obesity is not a new disease, with roots that can be traced back to 400 BC. However, with the staggering increase in individuals that are overweight and obese since the 1980s, now over a quarter of individuals in Europe and the Americas are classed as obese. This presents a global health problem that needs to be addressed with novel therapies. It is now well accepted that obesity is a chronic, low-grade inflammatory condition that could predispose individuals to a number of comorbidities. Obesity is associated with cardiovascular diseases (CVDs) and type 2 diabetes (T2D) as part of “the metabolic syndrome,” and as first identified by Dr Vauge, central distribution of white adipose tissue (WAT) is an important risk factor in the development of these diseases. Subsequently, visceral WAT (vWAT) was shown to be an important factor in this association with CVDs and T2D, and increasing inflammation. As the obese WAT expands, mainly through hypertrophy, there is an increase in inflammation that recruits numerous immune cells to the tissue that further exacerbate this inflammation, causing local and systemic inflammatory and metabolic effects. One of the main types of immune cell involved in this pathogenic process is pro-inflammatory M1 adipose tissue macrophages (ATMs). MicroRNAs (miRNAs) are a species of small RNAs that post-transcriptionally regulate gene expression by targeting gene mRNA, causing its degradation or translational repression. These miRNAs are promiscuous, regulating numerous genes and pathways involved in a disease, making them useful therapeutic targets, but also difficult to study. miR-34a has been shown to increase in the serum, liver, pancreas, and subcutaneous (sc)WAT of patients with obesity, non- alcoholic fatty liver disease (NAFLD) and T2D. Additionally, miR-34a has been shown to regulate a number of metabolic and inflammatory genes in numerous cell types, including those in macrophages. However, the role of miR-34a in regulating vWAT metabolism and inflammation is poorly understood. Hypothesis: miR-34a is dysregulated in the adipose tissue during obesity, causing dysregulation of metabolic and inflammatory pathways in adipocytes and ATMs that contribute to adipose inflammation and obesity’s comorbidities, particularly T2D. Method/Results: The role of miR-34a in adipose inflammation was investigated using a murine miR-34a-/- diet-induced obesity model, and primary in vitro models of adipocyte differentiation and inflammatory bone marrow-derived macrophages (BMDMs). miR-34a was shown to be ubiquitously expressed throughout the murine epididymal (e)WAT of obese high-fat diet (HFD)-fed WT mice and ob/ob mice, as well as omental WAT from patients with obesity. Additionally, miR-34a transcripts were increased in the liver and brown adipose tissue (BAT) of ob/ob and HFD-fed WT mice, compared to WT controls. When miR-34a-/- mice were fed HFD ad libitum for 24 weeks they were significantly heavier than their WT counterparts by the end of the study. Ex vivo examinations showed that miR-34a-/- eWAT had a smaller adipocyte area on chow, which significantly increased to WT levels during HFD-feeding. Additionally, miR-34a-/- eWAT showed basal increases in cholesterol and fatty acid metabolism genes Cd36, Hmgcr, Lxrα, Pgc1α, and Fasn. miR-34a-/- iBAT showed basal reductions in Cebpα and Cebpβ, with increased Pgc1α expression during HFD- feeding. The miR-34a-/- liver additionally showed increased basal transcript expression of Pgc1α, suggesting miR-34a may broadly regulate PGC1α. Accompanying the ex vivo changes in cholesterol and fatty acid metabolism genes, in vitro miR-34a-/- white adipocytes showed increased lipid content. An F4/80high macrophage population was identified in HFD-fed miR-34a-/- eWAT, with increased Il-10 transcripts and serum IL-5 protein. Following these ex vivo observations, BMDMs from WT mice upregulated miR-34a expression in response to TNFα stimulation. Additionally, miR-34a-/- BMDMs showed an ablated CXCL1 response to TNFα. Conclusion: These findings suggest miR-34a has a multi-factorial role in controlling a susceptibility to obesity, by regulating inflammatory and metabolic pathways, potentially through regulation of PGC1α.