Engineered alpha-defensin peptides display antimicrobial activity against oral pathogens

Introduction: Human alpha defensins are a family of neutrophil-derived antimicrobial peptides also known as human neutrophil peptides (HNPs). The defensin family of peptides are characterised by six invariant cysteine residues forming three disulphide bridges. The formation of the correct disulphide pairs complicates the synthesis of full length human alpha defensin and limits its therapeutic potential as an antimicrobial peptide. Objectives: The aim of this study was to determine whether truncated alpha defensins displayed antimicrobial activity against a range of micro-organisms including oral pathogens. Methods: Engineered peptides were synthesised by solid-phase methods using standard Fmoc chemistry. Antibacterial assays were performed using a previously described ultra sensitive radial diffusion method. A total of five engineered defensin peptides and full length alpha defensin were tested for their sensitivity against eight micro-organisms, including Gram negative bacteria, Gram positive bacteria and fungal pathogens Results: Antimicrobial activity was identified as clear zones around peptide-containing wells. Zone diameters were used to calculate minimum inhibitory concentrations (MICs) for each peptide. There was considerable variability in the susceptibility of the micro-organisms to the truncated analogues. Bacillus subtilis and Enterococcus faecalis were sensitive to the majority of the engineered peptides whereas Staphylococcus aureus, Escherichia coli and Candida albicans displayed resistance (defined as an MIC of greater than 250 ug/ml) to the truncated defensins. Of the five engineered peptides synthesised, the 2-aminobenzoic acid (Abz)-containing analogues based on the C-terminal sequence of alpha defensin displayed MIC values closest to that of the full length defensin in 5 out of 8 micro-organisms studied. Conclusion: This study demonstrates that truncated alpha defensins display variable antimicrobial activity against a range of micro-organisms, including oral pathogens. The generation of truncated defensins without disulphide bridges simplifies their synthesis and increases their therapeutic potential.

Eppin: A Novel Protein Possessing Antimicrobial Properties Against Oral Pathogens

Background: Epididymal protease inhibitor (eppin) is a dual motif protein belonging to the whey acidic protein (WAP) family. Although expressed in numerous different tissues, to date, its functional characterisation is limited. It has been shown to exhibit antibacterial activity against Gram-negative bacteria (Escherichia coli) and antiprotease activity against some proteases of the serine protease family. We are interested in determining the role of eppin in innate immune defence. Objectives: This study aims to determine eppin's potential function in the innate immune response in the oral cavity by investigating the antimicrobial activity of eppin against relevant oral pathogens. Methods: Eppin was recombinantly expressed in E. coli cells and purified by immobilised metal affinity chromatography (IMAC). The antimicrobial effects of the protein were then assessed against two oral pathogens, Fusobacterium nucleatum and Candida albicans, using a double layer radial diffusion assay. Results: Eppin displayed antimicrobial activities against both oral pathogens tested and these activities were shown to be comparable to the well characterised antimicrobial peptide, LL-37. The antifungal effects of eppin were shown to be more potent than those of the human cathelicidin, LL-37. Conclusions: Eppin has been shown to possess both antibacterial and antifungal properties against oral pathogens, suggesting an important role for this protein in the innate immune response in the oral cavity. This study furthers our knowledge of the physiological role exerted by eppin and its possible role in the modulation of chronic diseases such as periodontitis and oral candidiasis.

SPLI is a Chemoattractant for Oral and Skin Fibroblasts

Objectives: Unlike adult dermal wounds, the oral mucosa demonstrates preferential healing characterized by rapid remodeling and re-epithelialisation, with minimal scar formation. Secretory leukocyte protease inhibitor (SLPI) is an epithelial-derived factor with potential for promoting scarless repair. The aims of this study were to: (i) investigate the directed migratory (chemotaxis) response of oral and skin fibroblasts to various concentrations of SLPI; and (ii) compare migratory speed of the two cell types. Methods: Paired oral and skin fibroblasts were seeded at 2x104 cells in six well plates containing glass coverslips, and cultured in DMEM supplemented with 10% FCS for 48hours. Following a period of serum starvation (18hours in DMEM plus 0.5% BSA), coverslips were incorporated within a Dunn chemotaxis chamber containing DMEM with 0.5% BSA +/- SLPI gradients at 0.5, 1 or 2µM concentrations. Using microscopy, the migratory behaviour of cells was digitally captured every 10mins for 18hours, traced with JCell tracking software and resulting co-ordinates statistically analysed using Mathmatica software. Results: At all concentrations SLPI was a significant chemoattractant (p<0.01) for both cell types. However, skin fibroblasts migrated significantly faster than oral cells at each SLPI concentration, with greatest effect observed at the highest dose (skin: 32.0±0.47µm/hr, oral: 13.6±0.23µm/hr). Conclusion: SLPI is a chemoattractant for both oral and skin fibroblasts, and may play an important role in fibroblast recruitment during wound healing. This work was funded by the R&D Office, N.Ireland.

Victims, Violence and Voice: Transitional Justice, Oral History and Dealing with the Past

Transitional justice is concerned with the legal and social processes established to deal with the legacy of violence in post-conflict and post-authoritarian contexts. These processes are essentially “creatures of law” – they are established by statute, their work is molded and shaped by lawyers, and their outcomes are benchmarked against what is or is not acceptable in domestic and international law. Concerns have mounted in recent years about the dominance of legalism within the field and the instrumentalization of those most directly affected by past violence. A commonly prescribed – but as yet largely empirically untested – corrective is that transitional justice theory and practice must become more open to interdisciplinary insights and perspectives. The interview – in different guises, contexts and settings – is at the heart of most transitional justice processes. As a historian now working in a School of Law I reflect in this article on the theoretical and practical intersections between law, history, and the interview. Drawing on more than 200 interviews concerning the Northern Ireland conflict and six other international case studies I concentrate in particular on interview-based initiatives that purport to be “victim-centered”. Having identified three interrelated risks - the manipulation of victim voice by vested interests, the affording of authority to particular voices, and the reification or “freezing” of identity - and having related these to the constraints of legal mechanisms and a wider failure to manage victims’ expectations, I argue that a greater familiarity with oral history theory and praxis can usefully illuminate the tensions between legal and historical approaches to engaging voice, and ultimately offer guidance to the shared challenge of victim-centered transitional justice.

Justice, Truth and Oral History: Legislating the Past 'From Below' in Northern Ireland

Drawing on the ‘from below’ perspective which has emerged in transitional justice scholarship and practice
over the past two decades, this article critically examines the dealing with the past debate in Northern
Ireland. The paper begins by offering an outline of the from below perspective in the context of post-conflict
or post-authoritarian societies which are struggling to come to terms with past violence and human rights
abuses. Having provided some of the legal and political background to the most recent efforts to deal with
the past in Northern Ireland, it then critically examines the relevant past-related provisions of the Stormont
House Agreement, namely the institutions which are designed to facilitate ‘justice’, truth recovery and the
establishment of an Oral History Archive. Drawing from the political science and social movement
literature on lobbying and the ways in which interests groups may seek to influence policy, the paper then
explores the efforts of the authors and others to contribute to the broader public debate, including through
drafting and circulating a ‘Model Bill’ on dealing with the past (reproduced elsewhere in this issue) as a
counterweight to the legislation which is required from the British government to implement the Stormont
House Agreement. The authors argue that the combination of technical capacity, grass-roots
credibility and ‘international-savvy’ local solutions offers a framework for praxis from below in other
contexts where activists are struggling to extend ownership of transitional justice beyond political elites.
Keywords: transitional justice; from below; dealing with the past; legislation; truth
recovery; prosecutions; oral history

Oral Bisphosphonate Exposure and the Risk of Upper Gastrointestinal Cancers

The association between oral bisphosphonate use and upper gastrointestinal cancer has been controversial. Therefore, we examined the association with esophageal and gastric cancer within the Kaiser Permanente, Northern California population. A total of 1,011 cases of esophageal (squamous cell carcinoma and adenocarcinoma) and 1,923 cases of gastric adenocarcinoma (cardia, non-cardia and other) diagnosed between 1997 and 2011 from the Kaiser Permanente, Northern California cancer registry were matched to 49,886 and 93,747 controls, respectively. Oral bisphosphonate prescription fills at least one year prior to the index date were extracted. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between prospectively evaluated oral bisphosphonate use with incident esophageal and gastric cancer diagnoses with adjustment for potential confounders. After adjustment for potential confounders, no significant associations were found for esophageal squamous cell carcinoma (OR 0.88; 95% CI: 0.51, 1.52), esophageal adenocarcinoma (OR 0.68; 95% CI: 0.37, 1.24), or gastric non-cardia adenocarcinoma (OR 0.83, 95% CI: 0.59, 1.18), but we observed an adverse association with gastric cardia adenocarcinoma (OR 1.64; 95% CI: 1.07, 2.50). In conclusion, we observed no association between oral bisphosphonate use and esophageal cancer risk within a large community-based population. A significant association was detected with gastric cardia and other adenocarcinoma risk, although this needs to be replicated.

A Internet como Novo Meio de Comunicação para os Destinos Turísticos: O caso da Ilha da Madeira

Com o aparecimento da Internet, assiste-se cada vez mais ao nascimento e desenvolvimento de novos destinos turísticos. O novo meio de comunicação faz com que os consumidores aumentem os seus patamares de exigências e de expectativas. Ao poder público e às empresas privadas cabe-lhes o papel de sensibilizar o imaginário dos turistas para visitarem as suas comunidades e regiões e não outras. O presente artigo pretende analisar a importância que o poder local e regional da Madeira atribui à Internet para a divulgação dos seus municípios como destinos turísticos a serem fruídos. A pesquisa foi baseada em entrevistas e análise dos sites municipais. O trabalho de campo realizou-se de Janeiro de 2004 a Junho de 2004. Este artigo centra-se essencialmente na análise das entrevistas e está estruturado nos seguintes tópicos: Introdução à problemática; fundamentação teórica sobre a temática; análise das entrevistas e conclusão.

Comunicação pública em territórios rurais – perceções e participação dos atores globais em Avelãs de Cima

Vivemos num mundo cada vez mais globalizado e uma das consequências é a crescente concorrência que existe entre territórios, reforçando-se a necessidade de fazer chegar aos públicos interessados, um conjunto de atributos e diferenciações, suficientemente atrativos e apelativos, para que estes territórios sejam “consumidos”, não só pelo seu reconhecimento temporal, mas também pela forma como ele se comunica. Se até ao momento esta diferenciação era apenas explicitada numa base meramente turística (pelos impactos económicos positivos que normalmente se conseguem), hoje a estratégia deve seguir um plano de marketing capaz de atrair e fixar quer residentes, excursionistas, turistas e investidores, satisfazendo-os. Dos estudos realizados é comumente aceite que o sucesso da execução de um plano de marketing territorial assenta num modelo participativo que promova e antecipe necessidades e desejos dos atores globais e que valide e identifique os pontos fortes, para ajudar a desenvolver (definir e implementar) uma estratégia sustentável, a prazo. Então é relevante chamar ao processo estes atores (públicos e privados, residentes e visitantes) envolvendo-os nesta identificação, comprometendo-os também nos seus resultados.Com este artigo apresenta-se então um estudo de caso aplicado a um território rural, na freguesia de Avelãs de Cima, tendo sido utilizada como metodologia um inquérito por questionário a todos os atores. Enumeram-se os fatores relevantes identificados, assim como os que não se desejam ver aplicados, requisitos evidentes para iniciar uma nova política de comunicação pública. Deste trabalho já resultou uma nova abordagem pelos atores públicos locais, destacando a perspetiva de utilização de sinergias pela integração dos recursos de duas outras freguesias, estando em construção um projeto comum de rotas com base nos atributos dessas localidades.-----We live in an increasingly globalized world and one of the consequences is the increasing competition that exists between areas, reinforcing the need to reach out to stakeholders, a set of attributes and differences sufficiently attractive and appealing, so that these territories are "consumed ", not only by their temporal recognition, but also for how it communicates. If so far this differentiation was only explained in a purely tourist base (by the positive economic impacts that usually can get), today the strategy must follow a marketing plan able to attract and retain residents, hikers, tourists and investors. There are studies where is commonly accepted that the successful implementation of a territorial marketing plan based on a participatory model that promotes and anticipate needs and desires of the global players and validate and identify the strengths, to help develop (define and implement) one sustainable strategy in the long term. So it is relevant to call these actors (public and private, residents and visitors) involving them in this identification and also committing them in their results. With this article we present a case study applied to a rural area in the parish of Avelãs de Cima, having been used a survey methodology for all actors. All the relevant identified factors are listed, as well as those which do not wish to see applied, clear requirements to start a new policy of public communication. This work has resulted in a new approach by local public actors, highlighting the prospect of using synergies by integrating the features of two other parishes, under construction with a common design routes based on attributes of those localities.

Lo que cuento no es mi cuento: Cultura andina y tradición oral

Alfredo Mires asumió en 1982 la conducción de la Red de Bibliotecas Rurales de Cajamarca. Apuntaló desde entonces la organícidad y principios que ahora caracterizan este movimiento. Desde antes ya habia acompañado procesos de rescate cultural y sustentó el inicio de esta tarea al interior de la Red. En 1986, via asambleas y reuniones con campesinos y en las propias comunidades, fundó el Proyecto Enciclopedia Campesina. Fruto de esos andares es este trabajo, reflexión de la experiencia que afirma la convicción de mirar hacia las raices para seguir creciendo. Aquí se suman muchas lunas y soles, armadas con Ia hoja sagrada y caminatas interminables acompañando este proceso éducativo-cultural desde y con las propias comunidades campesinas. Lo que cuento no es mi cuento fue concebido inicialmente como una tesis, pero revisado y ampliado, precisa la concepción y la experiencia sostenida. Porque hablar del saber andino y de las experiencias mencionadas, es habitual de una población que vive, recrea, fortalece y recupera de manera permanente y desde siempre el equilibrio sagrado entre sociedad y naturaleza.

Turismo : meios de comunicação e promoção : o caso da Madeira

O turismo é uma importante ferramenta para desenvolver a economia da Ilha da Madeira. Neste ãmbito é necessário influenciar os turistas potenciais. Os municípios e as instâncias regionais devem ter um papel determinante na promoção da sua localidade como um destino turístico. Os meios de comunicação são essenciais para a promoção de um destino turístico. Entre os diferentes instrumentos de promoção, a Internet é um novo meio para disseminar as vantagens de certos lugares e regiões. Neste estudo, procura-se verificar e analisar o papel dos municípios da Madeira e da DRT na promoção da sua localidade como um destino turístico, via Internet. /*** Abstract - Tourism is an important tool to develop the economy of Madeira island. On that respect it is necessary to influence potential tourists. Municipalities and regional bodies must have an important role to promote the various tourism destinations. Media tools are essential for the promotion of the communities as tourism destinations. Among the different instruments of promotion Internet is a new way to promote, compete and disseminate the advantages of certain places and regions. In this study the approach is oriented to identify and analyse the role of Madeira municipalities in the promotion of their tourism locals, via Internet.

O processo de reconhecimento e validação de competências: o impacto da aquisição de competências em tecnologias de informação e comunicação de adultos

Esta investigação insere-se no âmbito geral do Projecto de investigação científica denominado “Novas Núpcias da Qualificação no Alentejo”, promovido pelo Centro de Investigação em Educação e Psicologia da Universidade de Évora. A sua finalidade é avaliar os impactos das TIC na vida dos adultos certificados pelo processo de RVCC. A metodologia utilizada, de carácter quantitativo, baseou-se num estudo descritivo utilizando, como instrumento de investigação, o inquérito por questionário, comum a todas as investigações das “Novas Núpcias da Qualificação no Alentejo”. Este instrumento foi aplicado aos indivíduos certificados entre 2001 e 2005, pelo processo de RVCC, nos seis Centros de RVCC do Alentejo. Dos resultados obtidos, ao nível da dimensão pessoal e profissional, dos indivíduos certificados no Centro de RVCC promovido pelo Centro de Formação Profissional de Portalegre do IEFP, destacamos, na utilização do Computador e da Internet, uma evolução mais significativa nas mulheres e um maior impacto na dimensão pessoal; ABSTRACT: This research falls within the general scope of the research project entitled "Novas Núpcias da Qualificação no Alentejo”, sponsored by the Investigation Centre in Education and Psychology at the University of Évora. Its purpose is to assess the impacts of ICTs in the lives of adults certified by the RVCC program. The methodology in use, the quantitative method, was based on a descriptive study using a research instrument, the questionnaire survey, common to all investigations of "Novas Núpcias da Qualificação no Alentejo". This instrument was administered to individuals certified between the years 2001 and 2005, within the RVCC process in the six RVCC Centres of Alentejo. From the results obtained, at a personal and professional dimension, within the individuals certified in the RVCC Centre sponsored by Vocational Training Centre of Portalegre of “IEFP”, we highlight the use of computer and internet, a most significant development in women and greater impact in the personal dimension.