Assigning dates to thin gneissic veins in high-grade metamorphic terranes: A cautionary tale from Akilia, southwest Greenland

A granodiorite from Akilia, southwest Greenland, previously suggested to date putative life-bearing rocks to greater than or equal to3.84 Ga, is re-investigated using whole-rock major and trace-element geochemistry, and detailed cathodoluminescence image-guided secondary ion mass spectrometer analyses of zircon U-Th-Pb and rare earth elements. Complex zircon internal structure reveals three episodes of zircon growth and/or recrystallization dated to c. 3.84 Ga, 3.62 Ga and 2.71 Ga. Rare earth element abundances imply a significant role for garnet in zircon generation at 3.62 Ga and 2.71 Ga. The 3.62 Ga event is interpreted as partial melting of a c. 3.84 Ga grey gneiss precursor at granulite facies with residual garnet. Migration of this 3.62 Ga magma (or melt-crystal mush) away from the melt source places a maximum age limit on any intrusive relationship. These early Archaean relationships have been complicated further by isotopic reworking in the 2.71 Ga event, which could have included a further episode of partial melting. This study highlights a general problem associated with dating thin gneissic veins in polyphase metamorphic terranes, where field relationships may be ambiguous and zircon inheritance can be expected.

Identification of a novel frameshift mutation in the giant muscle filament titin in a large Australian family with dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is an etiologically heterogeneous cardiac disease characterized by left ventricular dilation and systolic dysfunction. Approximately 25-30% of DCM patients show a family history of mainly autosomal dominant inheritance. We and others have previously demonstrated that mutations in the giant muscle filament titin (TTN) can cause DCM. However, the prevalence of titin mutations in familial DCM is unknown. In this paper, we report a novel heterozygous 1-bp deletion mutation (c.62890delG) in TTN that cosegregates with DCM in a large Australian pedigree (A3). The TTN deletion mutation c.62890delG causes a frameshift, thereby generating a truncated A-band titin due to a premature stop codon (p.E20963KfsX10) and the addition of ten novel amino acid residues. The clinical phenotype of DCM in kindred A3 demonstrates incomplete penetrance and variable expressivity. Finally, protein analysis of a skeletal muscle biopsy sample from an affected member did not reveal the predicted truncated titin isoform although the aberrant mRNA was present, suggesting posttranslational modification and degradation of the truncated protein. The identification of a novel disease-causing mutation in the giant titin gene in a third large family with DCM indicates that mutations in titin may account for a significant portion of the genetic etiology in familial DCM.

Strategies to obtain stable transgenic plants from non-embryogenic lines: complementation of the nn(1) mutation of the NORK gene in Medicago sativa MN1008

Strategies to introduce genes into non-embryogenic plants for complementation of a mutation are described and tested on tetraploid alfalfa (Medicago sativa). Genes conditioning embryogenic potential, a mutant phenotype, and a gene to complement the mutation can be combined using several different crossing and selection steps. In the successful strategy used here, the M. sativa genotype MnNC-1008(NN) carrying the recessive non-nodulating mutant allele nn(1) was crossed with the highly embryogenic alfalfa line Regen S and embryogenic hybrid individuals were identified from the F1 progeny. After transformation of these hybrids with the wild-type gene (NORK), an F2 generation segregating for the mutation and transgene were produced. Plants homozygous for the mutant allele and carrying the wild-type NORK transgene could form root nodules after inoculation with Sinorhizobium meliloti demonstrating successful complementation of the nn(1) mutation.

Transmission ratio distortion in the human body louse, Pediculus humanus (Insecta : Phthiraptera)

We studied inheritance at three microsatellite loci in eight F-1 and two F-2 families of the body (clothes) louse of humans, Pediculus humanus. The alleles of heterozygous female-parents were always inherited in a Mendelian fashion in these families. Alleles from heterozygous male-parents, however, were inherited in two different ways: (i) in a Mendelian fashion and (ii) in a non-Mendelian fashion, where males passed to their offspring only one of their two alleles, that is, 100% nonrandom transmission. In male body lice, where there was non-Mendelian inheritance, the paternally inherited set of alleles was eliminated. We interpret this pattern of inheritance as evidence for extreme transmission ratio distortion of paternal alleles in this species.

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.

Polycystic kidney disease in Bull Terriers: an autosomal dominant inherited disorder

The prevalence, mode of inheritance and urinalysis findings in Bull Terriers with polycystic kidney disease were assessed by screening 150 clinically normal dogs. The disorder was diagnosed in 39 dogs on the basis of renal ultrasound results and family history of the disease. In equivocal cases confirmation required gross and histopathological renal examination. Necropsy was performed on nine affected dogs and the kidneys from another five affected animals were also examined. Renal cysts were usually bilateral, occurred in cortex and medulla and varied from less than 1 mm to over 2.5 cm in diameter. Cysts were lined by epithelial cells of nephron origin. Abnormal urine sediment and proteinuria were common in affected dogs. The disease appears to be inherited in a highly penetrant autosomal dominant manner.

A formal framework for modelling and analysing mobile systems

This paper presents a formal framework for modelling and analysing mobile systems. The framework comprises a collection of models of the dominant design paradigms which are readily extended to incorporate details of particular technologies, i.e., programming languages and their run-time support, and applications. The modelling language is Object-Z, an extension of the well-known Z specification language with explicit support for object-oriented concepts. Its support for object orientation makes Object-Z particularly suited to our task. The system structuring techniques offered by object-orientation are well suited to modelling mobile systems. In addition, inheritance and polymorphism allow us to exploit commonalities in mobile systems by defining more complex models in terms of simpler ones.

Teaching principles of genetics through SNP analysis

An understanding of inheritance requires comprehension of genetic processes at all levels, from molecules to populations. Frequently genetics courses are separated into molecular and organismal genetics and students may fail to see the relationships between them. This is particularly true with human genetics, because of the difficulties in designing experimental approaches which are consistent with ethical restrictions, student abilities and background knowledge, and available time and materials. During 2005 we used analysis of single nucleotide polymorphisms (SNPs) in two genetic regions to enhance student learning and provide a practical experience in human genetics. Students scanned databases to discover SNPs in a gene of interest, used software to design PCR primers and a restriction enzyme based assay for the alleles, and carried out an analysis of the SNP on anonymous individual and family DNAs. The project occupied eight to ten hours per week for one semester, with some time spent in the laboratory and some spent in database searching, reading and writing the report. In completing their projects, students acquired a knowledge of Mendel’s first law (through looking at inheritance patterns), Mendel’s second law and the exceptions (the concepts of linkage and linkage disequilibrium), DNA structure (primer design and restriction enzyme analysis) and function (SNPs in coding and non-coding regions), population genetics and the statistical analysis of allele frequencies, genomics, bioinformatics and the ethical issues associated with the use of human samples. They also developed skills in presentation of results by publication and conference participation. Deficiencies in their understanding (for example of inheritance patterns, gene structure, statistical approaches and report writing) were detected and guidance given during the project. SNP analysis was found to be a powerful approach to enhance and integrate student understanding of genetic concepts.

Modelling Java concurrency with Object-Z

In this paper, we present a formal model of Java concurrency using the Object-Z specification language. This model captures the Java thread synchronization concepts of locking, blocking, waiting and notification. In the model, we take a viewpoints approach, first capturing the role of the objects and threads, and then taking a system view where we capture the way the objects and threads cooperate and communicate. As a simple illustration of how the model can, in general be applied, we use Object-Z inheritance to integrate the model with the classical producer-consumer system to create a specification directly incorporating the Java concurrency constructs.

Specification matching of object-oriented components

Object-orientation supports software reuse via features such as abstraction, information hiding, polymorphism, inheritance and redefinition. However, while libraries of classes do exist, one of the challenges that still remains is to locate suitable classes and adapt them to meet the specific requirements of the software developer. Traditional approaches to library retrieval are text-based; it is therefore difficult for the developer to express their requirements in a precise and unambiguous manner. A more promising approach is specification-based retrieval, where library component interfaces and requirements are expressed using a formal specification language. In this case retrieval is based on matching formal specifications. In this paper we describe how existing approaches to specification matching can be extended to handle object-oriented components.

UMA ÁNALISE EXEGÉTICA DA PORÇÃO DE MIQUEIAS 2,1-5: A SITUAÇÃO SOCIOECONÔMICA EM JUDÁ E SUAS IMPLICAÇÕES NA HERANÇA DOS CAMPONESES NA SEFELÁ JUDAÍTA NO SÉCULO VIII A.C.

Esta pesquisa procura examinar, à luz da metodologia exegética, a perícope de Miqueias 2,1-5, a fim de reconstruir o cenário no qual emergiu a dura crítica social do profeta. O texto apresenta, em sua análise literária, características de um dito profético coeso, em estilo poético. Sua estrutura encontra-se dividida em duas unidades (denúncia e castigo), sendo que cada uma das unidades possui outras duas subunidades (genérica e específica). O gênero literário harmoniza-se com um dito profético de julgamento geralmente conhecido como oráculo ai . A análise da dimensão histórica situa o acontecimento fundante em 701 a.C., na Sefelá judaíta. Numa análise investigativa do conteúdo da denúncia norteado pelo modelo teórico do modo de produção tributário, observa-se um conflito entre dois grupos. Nesse conflito, Miqueias faz uma acusação a um grupo de poder em Judá que planeja e executa ações criminosas contra a herança camponesa. O castigo descreve a conspiração e o plano divino contra esse grupo de poder. Javé havia planejado um mal idêntico ao que eles haviam cometido, desonra e privação de suas possessões. Os valores culturais de honra e vergonha subjazem a esse oráculo. Por descumprirem seus deveres junto a Javé e ao povo, os criminosos perderiam todos os seus direitos e, sobretudo, a honra perante a própria comunidade. Com base no modelo teórico do modo de produção tributário, constata-se que, na situação social em Judá no oitavo século, prevalecia um conflito entre campo e cidade. As comunidades aldeãs pagavam tributo à cidade em forma de produtos e serviços. A excessiva arrecadação de tributo e as falhas no sistema de ajuda mútua forçaram os indivíduos e famílias a contrair dívidas, a hipotecar suas terras herdadas dos pais e eventualmente perdê-las. O profeta Miqueias é o porta-voz do protesto da classe campesina que resolve reagir aos desmandos praticados pela elite citadina. Para ele, Javé escuta a queixa dos que estão sendo oprimidos e intervém na história tomando o partido do oprimido.(AU)