Screening the Schistosoma mansoni transcriptome for genes differentially expressed in the schistosomulum stage in search for vaccine candidates

Schistosomiasis affects more than 200 million people worldwide; another 600 million are at risk of infection. The schistosomulum stage is believed to be the target of protective immunity in the attenuated cercaria vaccine model. In an attempt to identify genes up-regulated in the schistosomulum stage in relation to cercaria, we explored the Schistosoma mansoni transcriptome by looking at the relative frequency of reads in EST libraries from both stages. The 400 genes potentially up-regulated in schistosomula were analyzed as to their Gene Ontology categorization, and we have focused on those encoding-predicted proteins with no similarity to proteins of other organisms, assuming they could be parasite-specific proteins important for survival in the host. Up-regulation in schistosomulum relative to cercaria was validated with real-time reverse transcription polymerase chain reaction (RT-PCR) for five out of nine selected genes (56%). We tested their protective potential in mice through immunization with DNA vaccines followed by a parasite challenge. Worm burden reductions of 16-17% were observed for one of them, indicating its protective potential. Our results demonstrate the value and caveats of using stage-associated frequency of ESTs as an indication of differential expression coupled to DNA vaccine screening in the identification of novel proteins to be further investigated as potential vaccine candidates.

Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease

There is evidence of increased systemic expression of active GSK3B in Alzheimer`s disease patients, which apparently is associated with the formation of senile plaques and neurofibrillary tangles. Due to its central role in the pathogenesis of AD, GSK3B is currently a promising target of the pharmaceutical industry. Whilst trials with specific GSK inhibitors in AD are under way, major attention has been focused on the neuroprotective effects of lithium. Whereas the direct and indirect inhibitory effects of lithium over GSK3 activity have been documented by several groups, its effects over Gsk3 transcription have not yet been addressed. We used quantitative PCR to evaluate the transcriptional regulation of Gsk3a and Gsk3b in lithium-treated primary cultures of rat cortical and hippocampal neurons. We found a significant and dose-dependent reduction in the expression of Gsk3b, which was specific to hippocampal cells. This same effect was further confirmed in vivo by measuring Gsk3 expression in different brain regions and in peripheral leukocytes of adult rats treated with lithium. Our studies show that LiCl can modulate Gsk3b transcription in vitro and in vivo. This observation suggest new regulatory effects of lithium over Gsk3b, contributing to the better understanding of its mechanisms of action, offering a new and complementary explanation for Gsk3b modulation and reinforcing its potential for the inhibition of key pathological pathways in Alzheimer`s disease.

Simple Question, Complex Answer : Pathways Towards a 50% Decrease in Building Energy Use

Addressing building energy use is a pressing issue for building sector decision makers across Europe. In Sweden, some regions have adopted a target of reducing energy use in buildings by 50% until 2050. However, building codes currently do not support as ambitious objectives as these, and novel approaches to addressing energy use in buildings from a regional perspective are called for. The purpose of this licentiate thesis was to provide a deeper understanding of most relevant issues with regard to energy use in buildings from a broad perspective and to suggest pathways towards reaching the long-term savings objective. Current trends in building sector structure and energy use point to detached houses constructed before 1981 playing a key role in the energy transition, especially in the rural areas of Sweden. In the Swedish county of Dalarna, which was used as a study area in this thesis, these houses account for almost 70% of the residential heating demand. Building energy simulations of eight sample houses from county show that there is considerable techno-economic potential for energy savings in these houses, but not quite enough to reach the 50% savings objective. Two case studies from rural Sweden show that savings well beyond 50% are achievable, both when access to capital and use of high technology are granted and when they are not. However, on a broader scale both direct and indirect rebound effects will have to be expected, which calls for more refined approaches to energy savings. Furthermore, research has shown that the techno-economic potential is in fact never realised, not even in the most well-designed intervention programmes, due to the inherent complexity of human behaviour with respect to energy use. This is not taken account of in neither current nor previous Swedish energy use legislation. Therefore an approach that considers the technical prerequisites, economic aspects and the perspective of the many home owners, based on Community-Based Social Marketing methodology, is suggested as a way forward towards reaching the energy savings target.

Deakin as a national leader in teaching and learning

Deakin University has set itself the ambitious goal of becoming a national leader in teaching and learning and in the provision of high quality flexible education. The Vice-Chancellor, Professor Sally Walker, recently reinforced the target of Deakin being in the top third of Australian universities in relation to teaching and learning by 2012.

Factors influencing attitudes to violence against women

Attitudes toward men's violence against women shape both the perpetration of violence against women and responses to this violence by the victim and others around her. For these reasons, attitudes are the target of violence-prevention campaigns. To improve understanding of the determinants of violence against women and to aid the development of violence-prevention efforts, this article reviews the factors that shape attitudes toward violence against women. It offers a framework with which to comprehend the complex array of influences on attitudes toward violent behavior perpetrated by men against women. Two clusters of factors, associated with gender and culture, have an influence at multiple levels of the social order on attitudes regarding violence. Further factors operate at individual, organizational, communal, or societal levels in particular, although their influence may overlap across multiple levels. This article concludes with recommendations regarding efforts to improve attitudes toward violence against women.

Explanations or justifications?

Western governments are the current target of terrorist revolt. But rather than learning from the past, they continue to hide behind a veneer of civilised values and moral purity. (on the eve of war).

Examining and quantifying the drivers behind alterations and extensions to commercial buildings in a central business district

The drive to undertake building adaptation has increased in momentum, the primary reason being adaptation can be less expensive than new build and conventionally result in faster project delivery times. The issue of sustainable development is another clear driver for adaptation and collectively buildings contribute around half of all greenhouse gas emissions. At the same time governments seek effective and efficient ways of reducing the contribution of cities to climate change and building adaptation appears to offer a practical means of reducing building-related emissions. One example is the ‘1200 building program’ which aims to increase adaptation rates with a target of 1200 city centre office adaptations by 2020 as part of the strategy to achieve carbon neutrality. Through a longitudinal examination of building adaptations it is possible to identify the nature and extent of typical levels of adaptation, as well as determining the inter-relationship between different types of adaptation and building attributes. Melbourne city centre was used for a case study which analysed 5290 building adaptation events between 1998 and 2008. The findings promote the adaptive reuse of buildings in specific circumstances and are directly applicable for increasing sustainability in the built environment. The case study focused on existing buildings in a global city to ensure relevance to urban centres where existing commercial buildings can become part of the solution to mitigate climate change.

Scaling-up foreign aid : will the 'big push' work?

International donors are substantially scaling-up aid programmes. At the same time, there are widespread reservations over how much aid recipient countries can use effectively. Such concerns are supported by the aid effectiveness literature which finds that there are limits to the amounts of aid recipients can efficiently absorb. This article demonstrates that a ‘big push’ in foreign aid will not lead to diminishing returns as long as donors get the inter-country allocation of aid right. This is true even if donors provide aid at levels equal to the well-known target of 0.7 per cent of their gross national income

Modelling urban growth futures within inner metropolitan Melbourne

In the light of the Victorian State Government's move towards the development of 'Plan Melbourne' - a new metropolitan planning strategy currently being prepared to take Melbourne forward to 2050 - the following paper attempts to address the issue of how an inner city target of 90,000 new dwellings (Inner Metropolitan Action Plan - IMAP Strategy 5) will impact on existing inner Melbourne activity centres. Working with the prospect of establishing a more compact city within the inner Melbourne region, the paper will focus on key suburbs within the Port Phillip area. Working with a 'Housing Variance Model' based on household structure and dwelling type, the paper will attempt to assess the impact on urban morphology as capacity is progressively altered through a range of built form permutations.

Working with 'housing variance' to model urban growth futures with inner metropolitan Melbourne

Continued population growth in Melbourne over the past decade has led to the development of a range of strategies and policies by State and Local levels of government to set an agenda for a more sustainable form of urban development. As the Victorian State government moves towards the development of 'Plan Melbourne', a new metropolitan planning strategy currently being prepared to take Melbourne forward to 2050, the following paper addresses the issue of how new residential built form will impact on and be accommodated in existing Inner Melbourne activity centres. Working with the prospect of establishing a more compact city in order to meet an inner city target of 90,000 new dwellings (Inner Metropolitan Action Plan - IMAP Strategy 5), the paper presents a 'Housing Variance Model' based on household structure and dwelling type. As capacity is progressively altered through a range of built form permutations, the research attempts to assess the impact on the urban morphology of a case study of four Major Activity Centres in the municipality of Port Phillip.

A helical conotoxin from Conus imperialis has a novel cysteine framework and defines a new superfamily

Cone snail venoms are a rich source of peptides, many of which are potent and selective modulators of ion channels and receptors. Here we report the isolation and characterization of two novel conotoxins from the venom of Conus imperialis. These two toxins contain a novel cysteine framework, C-C-C-CC-C, which has not been found in other conotoxins described to date. We name it framework XXIII and designate the two toxins im23a and im23b; cDNAs of these toxins exhibit a novel signal peptide sequence, which defines a new K-superfamily. The disulfide connectivity of im23a has been mapped by chemical mapping of partially reduced intermediates and by NMR structure calculations, both of which establish a I-II, III-IV, V-VI pattern of disulfide bridges. This pattern was also confirmed by synthesis of im23a with orthogonal protection of individual cysteine residues. The solution structure of im23a reveals that im23a adopts a novel helical hairpin fold. A cluster of acidic residues on the surface of the molecule is able to bind calcium. The biological activity of the native and recombinant peptides was tested by injection into mice intracranially and intravenously to assess the effects on the central and peripheral nervous systems, respectively. Intracranial injection of im23a or im23b into mice induced excitatory symptoms; however, the biological target of these new toxins has yet to be identified.

Interventions designed to promote exclusive breastfeeding in high-income countries: a systematic review

Worldwide, women fail to reach the recommended exclusive breastfeeding target of 6 months postpartum. The objective of this study was to present a conceptual and methodological synthesis of interventions designed to promote exclusive breastfeeding to 6 months in high-income countries.

Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes

Phenotypic screening is making a comeback in drug discovery as the maturation of chemical proteomics methods has facilitated target identification for bioactive small molecules. A limitation of these approaches is that time-consuming genetic methods or other means are often required to determine the biologically relevant target (or targets) from among multiple protein-compound interactions that are typically detected. Here, we have combined phenotypic screening of a directed small-molecule library with competitive activity-based protein profiling to map and functionally characterize the targets of screening hits. Using this approach, we identify carboxylesterase 3 (Ces3, also known as Ces1d) as a primary molecular target of bioactive compounds that promote lipid storage in adipocytes. We further show that Ces3 activity is markedly elevated during adipocyte differentiation. Treatment of two mouse models of obesity-diabetes with a Ces3 inhibitor ameliorates multiple features of metabolic syndrome, illustrating the power of the described strategy to accelerate the identification and pharmacologic validation of new therapeutic targets.

Graphene quantum dots directly generated from graphite via magnetron sputtering and the application in thin-film transistors

This work presents a novel method to prepare graphene quantum dots (GQDs) directly from graphite. A composite film of GQDs and ZnO was first prepared using the composite target of graphite and ZnO via magnetron sputtering, followed with hydrochloric acid treatment and dialysis. Morphology and optical properties of the GQDs were investigated using a number of techniques. The as-prepared GQDs are 4-12 nm in size and 1-2 nm in thickness. They also exhibited typical excitation-dependent properties as expected in carbon-based quantum dots. To demonstrate the potential applications of GQDs in electronic devices, pure ZnO and GQD-ZnO thin-film transistors (TFTs) using ZrOx dielectric were fabricated and examined. The ZnO TFT incorporating the GQDs exhibited enhanced performance: an on/off current ratio of 1.7 × 107, a field-effect mobility of 17.7 cm2/Vs, a subthreshold swing voltage of 90 mV/decade. This paper provides an efficient, reproducible and eco-friendly approach for the preparation of monodisperse GQDs directly from graphite. Our results suggest that GQDs fabricated using magnetron sputtering method may envision promising applications in electronic devices.

Implementação de CRM em indústria petroquímica de 2ª geração e análise do nível de satisfação do cliente resultante

A competitividade das empresas apresenta forte ligação com a qualidade do relacionamento com o cliente. Para competir em tempo real é preciso dotar a empresa de meios que permitam conhecer e relacionar-se de forma cada vez mais eficiente com os clientes. O uso intensivo da tecnologia é fator que contribui para que o relacionamento com o cliente se torne mais efetivo. CRM (Customer Relationship Management) faz uso da tecnologia de informação com o objetivo de desenvolver e gerenciar relações entre empresas e seus clientes, de forma individualizada e mutuamente benéfica. O presente trabalho refere-se à implementação de um sistema CRM, abrangendo as etapas de seleção da solução de CRM, definição do organograma, cronograma e metodologia de trabalho, redesenho dos processos de atendimento ao cliente e configuração do software. Também é objeto deste trabalho a verificação do nível de satisfação do cliente resultante. O estudo foi desenvolvido junto a uma empresa do setor petroquímico, caso pioneiro de implantação de CRM no país, considerando o segmento de mercado em análise. O texto discute a relação existente entre um sistema de CRM e a satisfação do cliente, apresentando os resultados de uma pesquisa de satisfação aplicada aos clientes da empresa em estudo.