How lifetimes shape epigenotype within and across generations

Despite our detailed characterization of the human genome at the level of the primary DNA sequence, we are still far from understanding the molecular events underlying phenotypic variation. Epigenetic modifications to the DNA sequence and associated chromatin are known to regulate gene expression and, as such, are a significant contributor to phenotype. Studies of inbred mice and monozygotic twins show that variation in the epigenotype can be seen even between genetically identical individuals and that this, in some cases at least, is associated with phenotypic differences. Moreover, recent evidence suggests that the epigenome can be influenced by the environment and these changes can last a lifetime. However, we also know that epigenetic states in real-time are in continual flux and, as a result, the epigenome exhibits instability both within and across generations. We still do not understand the rules governing the establishment and maintenance of the epigenotype at any particular locus. The underlying DNA sequence itself and the sequence at unlinked loci (modifier loci) are certainly involved. Recent support for the existence of transgenerational epigenetic inheritance in mammals suggests that the epigenetic state of the locus in the previous generation may also play a role. Over the next decade, many of these processes will be better understood, heralding a greater capacity for us to correlate measurable molecular marks with phenotype and providing the opportunity for improved diagnosis and presymptomatic healthcare.

Genetic and environmental influences on dentofacial structures and oral health: studies of Australian twins and their families

Our studies of the teeth and faces of Australian twins commenced at the School of Dentistry, The University of Adelaide in the early 1980s. There are now over 900 pairs of twins enrolled in our continuing investigations, together with 1200 relatives. There are 3 main cohorts of participants. The first cohort comprises around 300 pairs of teenage twins for whom various records have been collected, including dental casts, facial photographs, finger and palm prints and information on laterality, including handedness. The second cohort comprises around 300 pairs of twins who have been examined at 3 stages of dental development from approximately 4 years of age to about 14 years: at primary, mixed, and permanent dentition (excluding 3rd molars) stages. The most recent study of tooth emergence and oral health, for which we are currently recruiting twins, will provide a third cohort of around 500 twin pairs aged from around birth to 3 to 4 years of age. Our broad aim in these studies has been to improve our understanding of how genetic and environmental factors contribute to variation in dental and facial features, and to oral health. We have also used our data to investigate aspects of the determination of laterality, particularly the fascinating phenomenon of mirror imaging. We plan to maximize the use of the longitudinal data and DNA we have collected, and continue to collect, by performing genome-wide scans for putative genetic linkage peaks for a range of dental features, and then to test for association between a series of likely candidate genes and our phenotypes.

Non-major-histocompatibility-complex genetics of ankylosing spondylitis

There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-I gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-IA. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.

Effect of extrusion parameters on flavour retention, functional and physical properties of mixtures of starch and D-limonene encapsulated in milk protein

The purpose of this research was to investigate the retention of flavour volatiles encapsulated in water-insoluble systems during high temperature–short time extrusion process. A protein precipitation method was used to produce water-insoluble capsules encapsulating limonene, and the capsules were added to the extruder feed material (cornstarch). A twin-screw extruder was used to evaluate the effect of capsule level of addition (0–5%), barrel temperature (125–145 °C) and screw speed (145–175 r.p.m.) on extruder parameters (torque, die pressure, specific mechanical energy, residence time distribution) and extrudate properties [flavour retention, texture, colour, density, expansion, water absorption index, water solubility index (WSI)]. Capsule level had a significant effect on extrusion conditions, flavour retention and extrudate physical properties. Flavour retention increased with the increase in capsule level from 0% to 2.5%, reached a maximum value at capsule level of 2.5% and decreased when the capsule level increased from 2.5% to 5%. The die pressure, torque, expansion ratio, hardness and WSI exhibited the opposite effect with the presence of capsules.

Soil exploration by sorghum root systems in wide row cropping systems

Wide and ‘skip row’ row configurations have been used as a means to improve yield reliability in grain sorghum production. However, there has been little effort put to design of these systems in relation to optimal combinations of root system characteristics and row configuration, largely because little is known about root system characteristics. The studies reported here aimed to determine the potential extent of root system exploration in skip row systems. Field experiments were conducted under rain-out shelters and the extent of water extraction and root system growth measured. One experiment was conducted using widely-spaced twin rows grown in the soil. The other experiment involved the use of specially constructed large root observation chambers for single plants. It was found that the potential extent of root system exploration in sorghum was beyond 2m from the planted rows using conventional hybrids and that root exploration continued during grain filling. Preliminary data suggested that the extent of water extraction throughout this region depended on root length density and the balance between demand for, and supply of, water. The results to date suggest that simultaneous genetic and management manipulation of wide row production systems might lead to more effective and reliable production in specific environments. Further study of variation in root-shoot dynamics and root system characteristics is required to exploit possible opportunities.

BM+-tree: A hyperplane-based index method for high-dimensional metric spaces

In this paper, we propose a novel high-dimensional index method, the BM+-tree, to support efficient processing of similarity search queries in high-dimensional spaces. The main idea of the proposed index is to improve data partitioning efficiency in a high-dimensional space by using a rotary binary hyperplane, which further partitions a subspace and can also take advantage of the twin node concept used in the M+-tree. Compared with the key dimension concept in the M+-tree, the binary hyperplane is more effective in data filtering. High space utilization is achieved by dynamically performing data reallocation between twin nodes. In addition, a post processing step is used after index building to ensure effective filtration. Experimental results using two types of real data sets illustrate a significantly improved filtering efficiency.

Biodegradable starch-based nanocomposite packaging materials

Polymer processing experiments have been conducted with a twin screw extruder. Different formulations of starch-based nanocomposites are being tested in a pilot scale film blowing tower. The physical properties of different starch-based films have been examined with thermal and mechanical analysis and X-ray diffraction. The results show that the addition of organoclay significantly improves both the processing and tensile properties over the original starch blends. The mechanical and thermal properties of the blends are also sensitive to the scale the clay particles are dispersed.

Reweaving the Silk Road through outsourcing and offshoring: The need for an externalisation theory

The reweaving and repaving of the modern Silk Road passes through outsourcing and offshoring activities that have a profound impact on both global business psyche and landscape. Firms, in particular, and their global value chain are being shaped and reshaped through a complex concoction of vertical integration and disintegration. The boundary of the firm and the firm/market interface has been of interest to students of organisation and economics for some time. It has provided the context for Internalisation Theory. Within the new economy, the twin trends of globalisation and advancing technologies are giving rise to a hitherto unknown “worldwide market for market transactions? and increased opportunities for international expansion by firms via market-based modes of organisation. We describe these trends and offer an early modeling approach for explaining why some firm’s externalise the marginal transaction in the so-called new economy. The paper further draws attention on the need to articulate an “Externalisation Theory? that adequately accounts for the firm’s offshoring and outsourcing activities, and that parallels as well as complement “Internalisation Theory? for a full explanation of today’s firms behaviour.

Conflitos e Esperanças: um estudo em Gênesis 25-36 e na literatura profética da Bíblia Hebraica sobre a relação entre os descendentes de Esaú e Jacó

Na história da humanidade, a realidade de conflitos e de guerras entre povos vizinhos têm sido comum. O que mais assusta é o fato que, o discurso religioso, ao invés de desencorajar tais realidades pode incentivar e justificar os projetos de poder dessas nações. O estudo da Bíblia Hebraica pode lançar luzes para o entendimento das realidades de conflito entre nações e para o papel do discurso religioso nestes. Para isto, essa pesquisa propôs-se a estudar narrativas que abordam a origem e o desenvolvimento de rivalidades e de conflitos internacionais. Especialmente, estudou as narrativas familiares e os oráculos proféticos que abordaram a rivalidade, os conflitos e o ódio entre Israel/Judá e Edom para propor uma releitura capaz de encorajar projetos de paz. Os exercícios exegéticos nas narrativas familiares (Gn 35-36) e nos oráculos proféticos contra Edom (nas coleções de oráculos contra as nações, no livro de Obadias, e em perícopes de Is 63,1-6 e de Ml 1,2-5) abordaram o material literário da Bíblia Hebraica para investigar sobre a origem e o desenvolvimento dos conflitos entre Israel/Judá e Edom. Especial atenção foi dada ao estudo da construção histórica do ódio e o papel da literatura religiosa no crescente desenvolvimento das rivalidades, animosidades e conflitos. O primeiro capítulo estudou a saga de Isaque como documento histórico e teológico que abordou a origem familiar da rivalidade entre os irmãos gêmeos, com diferenças significativas na construção de suas vidas e identidades. O segundo capítulo estudou, na literatura profética, os Oráculos contra as Nações e, mais especificamente, os oráculos contra Edom. Nesta fase estudou a importância desse gênero literário na construção de uma teologia mais universal que atribuía a Deus o controle da história, visando maior cuidado com Israel. O terceiro capítulo também avaliou outro material profético que abordou o conflito e, até mesmo, o ódio divino contra os edomitas (Is 63,1-6 e Ml 1,2-5). Nestes, percebeu-se o acirramento dos conflitos e a construção de um discurso religioso mais animoso contra Edom. Os estudos nas narrativas de rivalidade e de conflitos entre Israel/Judá e Edom na Bíblia Hebraica procuraram destacar, na dinâmica história de conflitos, as esperanças de paz para as relações internacionais. Sobretudo, propôs reler esses textos para a construção de um discurso religioso-teológico que estimule a tolerância e a ética da paz.

OLHARES SOBRE O OUTRO Estudo das representações do Islã nos jornais Estado de S. Paulo e Folha de S. Paulo

A premissa do estudo compreende a existência de forças de poder nos retratos sobre o Islã no jornalismo internacional. Sabe-se que o Islã, em termos culturais e políticos, apresenta maior visibilidade a partir dos atos de 11 de setembro de 2001. Nesse sentido, a pesquisa entende que esse momento desempenha, na história, um fenômeno político de forte impacto e significação ideológica. Como objeto de análise, o estudo aborda as representações discursivas (Análise de Discurso) e as interconexões com (e do) Islã na Folha de S. Paulo e no Estado de S. Paulo, tendo por corpus o material publicado pelos jornais, na Editoria Internacional, nos 15 dias anteriores e posteriores à data que marcou, historicamente, os 10 anos do ataque às Torres Gêmeas. A tese também faz um inventário histórico-cultural da formação do Oriente Moderno e do Islã, da construção do Diferente na história e do Outro-Islã, além do resgate do jornalismo internacional. Observou-se, nas generalizações e nas simplificações das representações do Islã da mídia analisada, um retrato aproximado das ações dos fundamentalistas islâmicos, instruindo o contexto complexo do Islã como o Outro, o Diferente da história atual, denegando a ele suas atribuições culturais de autenticidade e de alteridade.

Efeito do laser de baixa intensidade no procedimento de expansão rápida da maxila

A proposta do presente estudo foi avaliar os efeitos do laser de baixa intensidade na regeneração óssea no procedimento de expansão rápida da maxila. Utilizou-se 27 indivíduos com média de idade de 10,2 anos, divididos em dois grupos: grupo laser (n=14), no qual se realizou a expansão rápida da maxila, associada ao laser e grupo sem laser (n=13), que realizou somente a expansão rápida da maxila. O protocolo de ativação do parafuso expansor foi de 1 volta completa no primeiro dia e ½ volta diária até a sobrecorreção. O laser utilizado foi o de diodo (TWIN Laser MMOptics®, São Carlos), seguindo o protocolo de aplicação: comprimento de onda de 780nm, potência de 40mW, densidade de 10J/cm2, em 10 pontos localizados ao redor da sutura palatina mediana. Os estágios de aplicação foram: L1 (do primeiro ao quinto dia de aplicação), L2 (travamento do parafuso e 3 dias seguidos), L3, L4 e L5 (após 7, 14 e 21 dias do L2, respectivamente). Radiografias oclusais da maxila foram realizadas com auxílio de uma escala de alumínio, para referencial densitométrico, em diferentes tempos: T1 (inicial), T2 (dia de travamento do parafuso), T3 (3 a 5 dias do T2), T4 (30 dias do T3), T5 (60 dias do T4). As radiografias foram digitalizadas e submetidas a um programa de imagem (Image Tool - UTHSCSA, Texas, USA), para mensuração da densidade óptica das áreas previamente selecionadas. Para realização do teste estatístico, utilizou-se a Análise de Covariância usando como covariável o tempo para a fase avaliada. Em todos os testes foi adotado nível de significância de 5% (p<0,05).Para o Grupo Laser, os dados mostram que houve uma queda significante de densidade durante a abertura do parafuso (T2-T1), um aumento significante da mesma no período final de avaliação (T5-T4), e um aumento também da densidade no período de regeneração propriamente dito (T5-T2), ou seja, a partir do momento em que finalizou a fase de abertura do parafuso expansor. Enquanto que no Grupo Sem Laser, a densidade não mostrou diferença estatisticamente significantemente em nenhum período analisado. Os resultados mostraram que o laser propiciou consideravelmente uma melhor abertura da sutura palatina mediana, além de influenciar no processo de regeneração óssea da sutura, acelerando seus processos de reparo.(AU)

Binocular contrast vision at and above threshold

A fundamental problem for any visual system with binocular overlap is the combination of information from the two eyes. Electrophysiology shows that binocular integration of luminance contrast occurs early in visual cortex, but a specific systems architecture has not been established for human vision. Here, we address this by performing binocular summation and monocular, binocular, and dichoptic masking experiments for horizontal 1 cycle per degree test and masking gratings. These data reject three previously published proposals, each of which predict too little binocular summation and insufficient dichoptic facilitation. However, a simple development of one of the rejected models (the twin summation model) and a completely new model (the two-stage model) provide very good fits to the data. Two features common to both models are gently accelerating (almost linear) contrast transduction prior to binocular summation and suppressive ocular interactions that contribute to contrast gain control. With all model parameters fixed, both models correctly predict (1) systematic variation in psychometric slopes, (2) dichoptic contrast matching, and (3) high levels of binocular summation for various levels of binocular pedestal contrast. A review of evidence from elsewhere leads us to favor the two-stage model. © 2006 ARVO.

Contrast discrimination with simultaneous monocular and dichoptic masks

In experiments reported elsewhere at this conference, we have revealed two striking results concerning binocular interactions in a masking paradigm. First, at low mask contrasts, a dichoptic masking grating produces a small facilitatory effect on the detection of a similar test grating. Second, the psychometric slope for dichoptic masking starts high (Weibull ß~4) at detection threshold, becomes low (ß~1.2) in the facilitatory region, and then unusually steep at high mask contrasts (ß~5.5). Neither of these results is consistent with Legge's (1984 Vision Research 24 385 - 394) model of binocular summation, but they are predicted by a two-stage gain control model in which interocular suppression precedes binocular summation. Here, we pose a further challenge for this model by using a 'twin-mask' paradigm (cf Foley, 1994 Journal of the Optical Society of America A 11 1710 - 1719). In 2AFC experiments, observers detected a patch of grating (1 cycle deg-1, 200 ms) presented to one eye in the presence of a pedestal in the same eye and a spatially identical mask in the other eye. The pedestal and mask contrasts varied independently, producing a two-dimensional masking space in which the orthogonal axes (10X10 contrasts) represent conventional dichoptic and monocular masking. The resulting surface (100 thresholds) confirmed and extended the observations above, and fixed the six parameters in the model, which fitted the data well. With no adjustment of parameters, the model described performance in a further experiment where mask and test were presented to both eyes. Moreover, in both model and data, binocular summation was greater than a factor of v2 at detection threshold. We conclude that this two-stage nonlinear model, with interocular suppression, gives a good account of early binocular processes in the perception of contrast. [Supported by EPSRC Grant Reference: GR/S74515/01]