α-Synuclein pathology in very elderly Finns : A population-based clinico-neuropathologic and molecular genetic study of Dementia with Lewy bodies

Populations in developed countries are ageing fast. The elderly have the greatest incidence of de-mentia, and thus the increase in the number of demented individuals, increases the immediate costs for the governments concerning healthcare and hospital treatment. Attention is being paid to disorders behind cognitive impairment with behavioural and psychological symptoms, which are enormous contributors to the hospital care required for the elderly. The highest dreams are in prevention; however, before discovering the tools for preventing dementia, the pathogenesis behind dementia disorders needs to be understood. Dementia with Lewy bodies (DLB), a relatively recently discovered dementia disorder compared to Alzheimer’s disease (AD), is estimated to account for up to one third of primary degenerative dementia, thus being the second most common cause of dementia in the elderly. Nevertheless, the impact of neuropathological and genetic findings on the clinical syndrome of DLB is not fully established. In this present series of studies, the frequency of neuropathological findings of DLB and its relation to the clinical findings was evaluated in a cohort of subjects with primary degenerative dementia and in a population-based prospective cohort study of individuals aged 85 years or older. α-synuclein (αS) immunoreactive pathology classifiable according to the DLB consensus criteria was found in one fourth of the primary degenerative dementia subjects. In the population-based study, the corresponding figure was one third of the population, 38% of the demented and one fifth of the non-demented very elderly Finns. However, in spite of the frequent discovery of αS pathology, its association with the clinical symptoms was quite poor. Indeed, the common clinical features of DLB, hypokinesia and visual hallucinations, associated better with the severe neurofibrillary AD-type pathology than with the extensive (diffuse neocortical) αS pathology when both types of pathology were taken into account. The severity of the neurofibrillary AD-type pathology (Braak stage) associated with the extent of αS pathology in the brain. In addition, the genetic study showed an interaction between tau and αS; common variation in the αS gene (SNCA) associated significantly with the severity of the neurofibrillary AD-type pathology and nominally significantly with the extensive αS pathology. Further, the relevance and temporal course of the substantia nigra (SN) degeneration and of the spinal cord αS pathology were studied in relation to αS pathology in the brain. The linear association between the extent of αS pathology in the brain and the neuron loss in SN suggests that in DLB the degeneration of SN proceeds as the αS pathology extends from SN to the neocortex instead of early destruction of SN seen in Parkinson’s disease (PD). Furthermore, the extent of αS pathology in the brain associated with the severity of αS pathology in the thoracic and sacral autonomic nuclei of the spinal cord. The thoracic αS pathology was more common and more severe compared to sacral cord, suggesting that the progress of αS pathology proceeds downwards from the brainstem towards the sacral spinal cord.

African mahogany (Khaya senegalensis) plantations in Australia - status, needs and progress

The Australian African mahogany estate comprises over 12,000 ha of industrial plantations, farm-forestry plots and trials, virtually all derived from Africa-sourced wild seed. However, the better trees have given high-value products such as veneers, high-grade boards and award-winning furniture. Collaborative conservation and improvement by the Northern Territory (NT) and Queensland governments since 2000 realised seed orchards, hedge gardens and genetic tests revealing promising clones and families. Private sector R&D since the mid 2000s includes silvicultural-management and wood studies, participatory testing of government material and establishing over 90 African provenances and many single-tree seedlots in multisite provenance and family trials. Recent, mainly public sector research included a 5-agency project of 2009-12 resulting in advanced propagation technologies and greater knowledge of biology, wood properties and processing. Operational priority in the short term should focus on developing seed production areas and ‘rolling front’ clonal seed orchards. R&D priorities should include: developing and implementing a collaborative improvement strategy based on pooled resources; developing non-destructive evaluation of select-tree wood properties, micropropagation (including field testing of material from this source) to ‘industry ready’ and a select-tree index; optimising seed production in orchards; advancing controlled pollination techniques; and maximising benefits from the progeny, clone and provenance trials. Australia leads the world in improvement and ex situ conservation of African mahogany based on the governments’ 13-year program and more recent industry inputs such that accumulated genetic resources total over 120 provenances and many families from 15 of the 19 African countries of its range. Having built valuable genetic resources, expertise, technologies and knowledge, the species is almost ‘industry ready’. The industry will benefit if it exploits the comparative advantage these assets provide. However the status of much of the diverse germplasm introduced since the mid 2000s is uncertain due to changes in ownership. Further, recent reductions of government investment in forestry R&D will be detrimental unless the industry fills the funding gaps. Expansion and sustainability of the embryonic industry must capitalise on past and current R&D, while initiating and sustaining critical new work through all-stakeholder collaboration.

Genetic studies on Finnish lupus erythematosus patients with cutaneous manifestations

Lupus erythematosus (LE) is a chronic, heterogeneous autoimmune disorder with abnormal immune responses, including production of autoantibodies and immune complexes. Clinical presentations of the disease range from mild cutaneous manifestations to a more generalised systemic involvement of internal organs. Cutaneous (CLE) forms are further subclassified into discoid LE (DLE), subacute cutaneous LE (SCLE) and acute cutaneous lupus erythematosus (ACLE), and may later progress to systemic disease (SLE). Both genetic and environmental factors contribute to the disease, although the precise aetiology is still elusive. Furthermore, complex gene-gene or gene-environment interactions may result in different subphenotypes of lupus. The genetic background of CLE is poorly known and only a few genes are confirmed, while the number of robust genetic associations in SLE exceeds 30. The aim of this thesis was to characterise the recruited patients clinically, and identify genetic variants conferring susceptibility to cutaneous variants of LE. Given that cutaneous and systemic disease may share underlying genetic factors, putative CLE candidate genes for genotyping were selected among those showing strong evidence of association in SLE. The correlation between relevant clinical manifestations and risk genotypes was investigated in order to find specific subphenotype associations. In addition, epistatic interactions in SLE were studied. Finally, the role of tissue degrading matrix metalloproteinases (MMP) in LE tissue injury was explored. These studies were conducted in Finnish case-control and family cohort, and Swedish case-control cohort. The clinical picture of the patients in terms of cutaneous, haematological and immunological findings resembled that described in the contemporary literature. However, the proportion of daily smokers was very high supporting the role of smoking in disease aetiology. The results confirmed that, even though clinically distinct entities, CLE and SLE share predisposing genetic factors. For the first time it was shown that known SLE susceptibility genes IRF5 and TYK2 also increase the risk of CLE. A tendency toward gene-gene interaction between these genes was found in SLE. As a remarkable novel finding, it was observed that ITGAM polymorphisms associated even more strongly to DLE than SLE, and the risk estimates were substantially higher than those reported for SLE. Several other recently identified SLE susceptibility genes showed signs of good or modest association especially in DLE. Subphenotype analyses indicated possible associations to clinical features, but marginally significant results reflected lack of sufficient power for these studies. Thorough immunohistochemical analyses of several MMPs demonstrated a role in epidermal changes and dermal tissue remodelling in diseased skin, and suggested that targeted action using selective MMP inhibitors may reduce lupus-induced damage in inflamed tissues. In conclusion, the results provide an insight into the genetics of CLE and demonstrate that genetic predisposition is at least in part shared between cutaneous and systemic variants of LE. This doctoral study has contributed IRF5, TYK2, ITGAM and several other novel genes to the so far short list of genes implicated in CLE susceptibility. Detailed examination of the function of these genes in CLE pathogenesis warrants further studies. Furthermore, the results support the need of subphenotype analysis with sample sizes large enough to reveal possible specific disease associations in order to better understand the heterogeneous nature and clinical specificities of the disease. Comprehensive analysis of clinical data suggests that smoking is an environmental triggering factor.

Genetic improvement and utilisation of indigenous tilapia in southern Africa: final technical report, December 1st 1998 to June 31st, 2002

Mozambique tilapia (Oreochromis mossambicus) is an indigenous tilapia species in southern Africa, until now the majority of genetic research has been carried out on Asian species of tilapia but this project aims to look at this African species. Those most suited to further development in aquaculture in southern Africa have now been identified. The genetic characterisation of strains has been completed. This information has aided the choice of strains for use in small scale aquaculture and for genetically male tilapia (GMT) production. They will form the basis of future strategies for further genetic improvement, and management of genetic diversity of Mozambique tilapia. The information will also contribute towards responsible management and development of genetic resources, particularly with regard to indigenous species of tilapia. Good progress has been made with the adaptation and implementation of producing the supermale fish required to produce all male offspring, resulting in faster growing populations of tilapia. The presence of the project and its associated activity has been a catalyst for a surge in interest in tilapia culture throughout southern Africa. [PDF contains 183 pages]

Progress toward a global genealogy of common carp (Cyprinus carpio L.) strains using mitochondrial nucleotide sequences data

As part of a study of genetic variation in the Vietnamese strains of the common carp (Cyprinus carpio L.) using direct DNA sequencing of mitochondrial control and ATPase6/8 gene regions, samples from a number of other countries were analyzed for comparison. Results show that the levels of sequence divergence in common carp is low on a global scale, with the Asian carp having the highest diversity while Koi and European carp are invariant. A genealogical analysis supports a close relationship among Vietnamese, Koi, Chinese Color and, to a lesser extent, European carp. Koi carp appear to have originated from a strain of Chinese red carp. There is considerable scope to extend this research through the analysis of additional samples of carp from around the world, especially from China, in order to generate a comprehensive global genealogy of common carp strains.

Genetic fingerprinting of plankton community provides new insights into aquatic ecology

Over the past two decades, molecular techniques have been widely used in ecological study and molecular ecology has been one of the most important branches of ecology. Meanwhile, genetic fingerprinting analyses have significantly enhanced our knowledge of the diversity and evolutionary relations of the planktonic organisms. Compared with conventional approaches in ecological study (e. g. morphological classification), genetic fingerprinting techniques are simpler and much more effective. This review provides an overview of the principles, advantages and limitations of the commonly used DNA fingerprinting techniques in plankton research. The aim of this overview is to assess where we have been, where we are now and what the future holds for solving aquatic ecological problems with molecular-level information.

Genome mapping in aquatic animals: Progress and future perspectives

The genome of aquatic animals is poorly understood and information from different taxonomic groups is sketchy. While there have been intensive genomic studies on some fish models, investigations on other fishes and invertebrates have been scarce. Yet there are recently some coordinated studies on genome mapping in a number of aquaculture animals of economic importance. This review summarizes information available on genome mapping of the important fish models and aquaculture animals. The future perspectives of this field of studies are discussed.

Review of genetic engineering of Laminaria japonica (Laminariales, Phaeophyta) in China

Progress has been made in establishing a genetic transformation model for Laminaria japonica (Phaeophyta, Laminariales). The model includes introduction of foreign genes by biolistic bombardment, use of promoter SV40 to drive gene expression, algal regeneration by parthenogenesis and selection by chloramphenicol or hygromycin.

Genetic structure of whiting (Merlangius merlangus) in the north east Atlantic and adjacent waters

Accurate identification of stock boundaries is essential for efficient fisheries management, hence the present study focused on the genetic structure of whiting. To this aim, 488 individuals collected from the southern Bay of Biscay to the southern Norwegian coast were genotyped using seven microsatellites. A low level of genetic structuring was detected in Atlantic waters since only the Bay of Biscay differentiated from more northern samples. The lack of genetic structure along the western margin of the British Isles is consistent with a high level of passive transport of pelagic eggs and larvae due to the combined influence of the North Atlantic Current and the Shelf Edge Current. High levels of dispersal could also occur between the western British Isles and the North Sea through both the branching of the North Atlantic Current into the northern North Sea and from the residual current flowing from the English Channel to the Southern Bight. In contrast, a significant genetic structure was identified within the North Sea, and this may be associated with the complex oceanography of this basin and retention systems reducing larval dispersal. In addition, considering also genetic, phenotypic and tag-recapture data collected on whiting, a learned homing behaviour of adults toward spawning areas may be hypothesised.

Genetic and migratory evidence for sympatric spawning of tropical Pacific eels from Vanuatu

The spawning areas of tropical anguillid eels in the South Pacific are poorly known, and more information about their life histories is needed to facilitate conservation. We genetically characterized 83 out of 84 eels caught on Gaua Island (Vanuatu) and tagged 8 eels with pop-up satellite transmitters. Based on morphological evidence, 32 eels were identified as Anguilla marmorata, 45 as A. megastoma and 7 as A. obscura. Thirteen of these eels possessed a mitochondrial DNA sequence (control region, 527 bp) or nuclear haplotype (GTH2b, 268 bp) conflicting with their species designation. These individuals also had multi-locus genotypes (6 microsatellite loci) intermediate between the species, and 9 of these eels further possessed heterozygote genotypes at species-diagnostic nuclear single nucleotide polymorphisms (SNPs). We classified these individuals as possibly admixed between A. marmorata and A. megastoma. One A. marmorata and 1 A. megastoma migrated 634 and 874 km, respectively, towards the border between the South Equatorial Current and the South Equatorial Counter Current. Both species descended from around 200 m depth at night to 750 m during the day. Lunar cycle affected the upper limit of migration depths of both species. The tags remained attached for 3 and 5 mo and surfaced <300 km from the pop-up location of a previously tagged A. marmorata pop-up location. A salinity maximum at the pop-up locations corresponding to the upper nighttime eel migration depths may serve as a seamark of the spawning area. The similar pop-up locations of both species and the evidence for admixture suggest that these tropical eels share a sympatric spawning area.

Review of Aerospace Engineering Cost Modelling: The Genetic Causal Approach

The primary intention of this paper is to review the current state of the art in engineering cost modelling as applied to aerospace. This is a topic of current interest and in addressing the literature, the presented work also sets out some of the recognised definitions of cost that relate to the engineering domain. The paper does not attempt to address the higher-level financial sector but rather focuses on the costing issues directly relevant to the engineering process, primarily those of design and manufacture. This is of more contemporary interest as there is now a shift towards the analysis of the influence of cost, as defined in more engineering related terms; in an attempt to link into integrated product and process development (IPPD) within a concurrent engineering environment. Consequently, the cost definitions are reviewed in the context of the nature of cost as applicable to the engineering process stages: from bidding through to design, to manufacture, to procurement and ultimately, to operation. The linkage and integration of design and manufacture is addressed in some detail. This leads naturally to the concept of engineers influencing and controlling cost within their own domain rather than trusting this to financers who have little control over the cause of cost. In terms of influence, the engineer creates the potential for cost and in a concurrent environment this requires models that integrate cost into the decision making process.

Genetic parentage in the squat lobsters Munida rugosa and M. sarsi (Crustacea, Anomura, Galatheidae)

Munida is the most diverse and cosmopolitan genus of the galatheid squat lobsters. The group has attracted much attention in recent years from both systematic and evolutionary perspectives, yet information on the biology, ecology, and evolution of this genus is very limited. We investigated the genetic parentage of two North Atlantic species; Munida rugosa and M. sarsi sampled from the Clyde Sea on the west coast of Scotland. Microsatellite markers were used to establish the parental contribution from embryos of berried females (M. rugosa, n=25 and M. sarsi, n=5). The frequency of multiple paternity observed in both species (86% for M. rugosa and 100% for M. sarsi) is the highest ever reported for any marine crustaceans. Invariably more than two sires were involved in each case (minimum of two to three for M. rugosa and four for M. sarsi). Findings indicate that multiple paternity is likely to be the norm in both species. Within most multiply sired broods, sire contribution was highly skewed towards a single male (66% of broods for M. rugosa and 100% for M. sarsi). Furthermore, embryos from different sires were randomly distributed across the female's brood patch. This is the first report of multiple paternity in galatheids. While a number of theories can account for the high incidence of multiple paternity in these species (e.g. convenience polyandry as a result of cryptic female choice, forced copulations, the influence of fishing pressures), at present it is not possible to disentangle their individual and/or combined effects.

Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes

Hyperglycemia plays a pivotal role in the development and progression of vascular complications, which are the major sources of morbidity and mortality in diabetes. Furthermore, these vascular complications often persist and progress despite improved glucose control, possibly as a result of prior episodes of hyperglycemia. Epigenetic modifications mediated by histone methyltransferases are associated with gene-activating events that promote enhanced expression of key proinflammatory molecules implicated in vascular injury. In this study, we investigated genetic polymorphisms of the SETD7, SUV39H1, and SUV39H2 methyltransferases as predictors of risk for micro- and macrovascular complications in type 1 diabetes.

A markerless deletion method for genetic manipulation of Burkholderia cenocepacia and other multidrug-resistant gram-negative bacteria

Genetic manipulation of multidrug-resistant bacteria is often difficult and hinders progress in understanding their physiology and pathogenesis. This book chapter highlights advances in genetic manipulation of Burkholderia cenocepacia, which are also applicable to other members of the Burkholderia cepacia complex and multidrug-resistant gram-negative bacteria of other genera. The method detailed here is based on the I-SceI homing endonuclease system, which can be efficiently used for chromosomal integration, deletion, and genetic replacement. This system creates markerless mutations and insertions without leaving a genetic scar and thus can be reused successively to generate multiple modifications in the same strain.

An efficient genetic algorithm for the design optimization of cold-formed steel portal frame buildings

The design optimization of a cold-formed steel portal frame building is considered in this paper. The proposed genetic algorithm (GA) optimizer considers both topology (i.e., frame spacing and pitch) and cross-sectional sizes of the main structural members as the decision variables. Previous GAs in the literature were characterized by poor convergence, including slow progress, that usually results in excessive computation times and/or frequent failure to achieve an optimal or near-optimal solution. This is the main issue addressed in this paper. In an effort to improve the performance of the conventional GA, a niching strategy is presented that is shown to be an effective means of enhancing the dissimilarity of the solutions in each generation of the GA. Thus, population diversity is maintained and premature convergence is reduced significantly. Through benchmark examples, it is shown that the efficient GA proposed generates optimal solutions more consistently. A parametric study was carried out, and the results included. They show significant variation in the optimal topology in terms of pitch and frame spacing for a range of typical column heights. They also show that the optimized design achieved large savings based on the cost of the main structural elements; the inclusion of knee braces at the eaves yield further savings in cost, that are significant.