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.

Self-condensation of a thiazole-peptide bearing a 21-membered loop into a library of giant macrocycles with multiple orthogonal loops

Tetrapeptide analogue H-[Glu-Ser-Lys(Thz)]-OH, containing a turn-inducing thiazole constraint, was used as a template to produce a 21-membered structurally characterized loop by linking Glu and Lys side chains with a Val-Ile dipeptide. This template was oligomerized in one pot to a library (cyclo-[1](n), n = 2-10) of giant symmetrical macrocycles (up to 120-membered rings), fused to 2-10 appended loops that were carried intact through multiple oligomerization (chain extension) and cyclization (chain terminating) reactions of the template. A three-dimensional solution structure for cyclo-[1](3) shows all three appended loops projecting from the same face of the macrocycle. This is a promising approach to separating pepticle motifs over large distances.

Thelastomatoidea (Nematoda : Oxyurida) of the Australian giant burrowing cockroach, Macropanesthia rhinoceros (Blaberidae : Geoscapheinae)

The thelastomatoid fauna of Macropanesthia rhinoceros was examined from 13 localities across its range in Queensland, Australia. Nine species of thelastomatoids, including two representing new genera, Geoscaphenema megaovum n. g., n. sp. and Jaidenema rhinoceratum n. g., n. sp., were found. Macropanesthia rhinoceros is reported as a new host for seven species previously recorded from Panesthia cribrata (Blaberidae: Panesthiinae) and P. tryoni tryoni, viz, Blattophila sphaerolaima, Leidynemella fusiformis, Cordonicola gibsoni, Travassosinema jaidenae, Coronostoma australiae, Hammerschmidtiella hochi and Desmicola ornata. Overall estimated richness for the system ranged from 10.1-13.5 species. The high degree of parasite faunal overlap between M. rhinoceros and the two Panesthia species is surprising given the disparate ecological niches that they occupy; P. cribrata and P. tryoni tryoni burrow in, and feed upon, moist decaying wood and require a climate that is moist all year round, whereas M. rhinoceros burrows in loose soil, feeds on fallen leaf litter and is tolerant of much drier environments.

Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice

Mammalian placentation is dependent upon the action of trophoblast cells at the time of implantation. Appropriate fetal growth, regulated by maternal nutrition and nutrient transport across the placenta, is a critical factor for adult offspring long-term health. We have demonstrated that a mouse maternal low-protein diet (LPD) fed exclusively during preimplantation development (Emb-LPD) increases offspring growth but programmes adult cardiovascular and metabolic disease. In this study, we investigate the impact of maternal nutrition on post-implantation trophoblast phenotype and fetal growth. Ectoplacental cone explants were isolated at day 8 of gestation from female mice fed either normal protein diet (NPD: 18% casein), LPD (9% casein) or Emb-LPD and cultured in vitro. We observed enhanced spreading and cell division within proliferative and secondary trophoblast giant cells (TGCs) emerging from explants isolated from LPD-fed females when compared with NPD and Emb-LPD explants after 24 and 48 h. Moreover, both LPD and Emb-LPD explants showed substantial expansion of TGC area during 24-48 h, not observed in NPD. No difference in invasive capacity was observed between treatments using Matrigel transwell migration assays. At day 17 of gestation, LPD- and Emb-LPD-fed conceptuses displayed smaller placentas and larger fetuses respectively, resulting in increased fetal:placental ratios in both groups compared with NPD conceptuses. Analysis of placental and yolk sac nutrient signalling within the mammalian target of rapamycin complex 1 pathway revealed similar levels of total and phosphorylated downstream targets across groups. These data demonstrate that early post-implantation embryos modify trophoblast phenotype to regulate fetal growth under conditions of poor maternal nutrition.

On the shoulders of a giant:his legacy will live on

Editorial

Waking the sleeping giant: Beliefs of Brazilian and *American teachers concerning liberation curriculum

The school curriculum is a matter mandated by the educational system rather than determined by the school stakeholders of a community, as Freire (1993) suggests. At the present time, one significant vision of school is challenging the current order of curriculum practice. It focuses on school as a liberating agency grounded on the belief that the abilities to access information and to think critically about it will educate an individual capable of making independent decisions. This dissertation investigates teacher's beliefs concerning curriculum. It was assumed that there is a discrepancy between what has been the position proposed by critical theorists including Freire (1998a, 1993); Apple (1979); Giroux (1998), and the position on curriculum which school systems are typically advancing. ^ There were four purposes of this study. The major purpose of this study was to determine whether or not Brazilian and American Teachers believe that a school curriculum based on Freirean principles could be implemented in the schools in which they worked. Also, this study sought to determine the differences found between teachers' beliefs in the Brazilian and American contexts. Another purpose was to determine how Brazilian and American teachers justify their beliefs and actions when these may represent conflicting values. Finally, this study sought to determine if these teachers believe that the curriculum is in need of change or if they accept the current curriculum as adequate. This study consisted of quantitative and qualitative data collection through multiple methods involving surveys and interviews. The study involved 171 teachers (88 Brazilian and 83 American) from multiple settings with the majority working for public systems. Overall, it seems that Brazilian and American teachers believe that a curriculum based on Freirean principles of education can be implemented in their schools, if ongoing education is provided. The majority of Brazilian teachers believe a curriculum change is necessary while half of the American teachers believe a curriculum change is needed and the other half seems to believe curriculum is adequate. Teachers explain that it is hard to implement a curriculum they believe to be most appropriate for students because the current curriculum is mandated by the school system or by national guidelines. The majority of Brazilian teachers and those American teachers who believed a curriculum change is necessary explained their rationale for change in terms of social justice, problem-solving, collective work, student-centered and context-based curriculum. American teachers, who believed that the curriculum is adequate, explained that they are satisfied with their student's achievements. They stated that their students are doing well on tests and are learning what is required. ^

Giant piezoresistance in silicon-germanium alloys

We use first-principles electronic structure methods to show that the piezoresistive strain gauge factor of single-crystalline bulk n-type silicon-germanium alloys at carefully controlled composition can reach values of G = 500, three times larger than that of silicon, the most sensitive such material used in industry today. At cryogenic temperatures of 4 K we find gauge factors of G = 135 000, 13 times larger than that observed in Si whiskers. The improved piezoresistance is achieved by tuning the scattering of carriers between different (Delta and L) conduction band valleys by controlling the alloy composition and strain configuration.

Giant enhancement of n-type carrier mobility in highly strained germanium nanostructures

First-principles electronic structure methods are used to predict the rate of n-type carrier scattering due to phonons in highly-strained Ge. We show that strains achievable in nanoscale structures, where Ge becomes a direct bandgap semiconductor, cause the phonon-limited mobility to be enhanced by hundreds of times that of unstrained Ge, and over a thousand times that of Si. This makes highly tensile strained Ge a most promising material for the construction of channels in CMOS devices, as well as for Si-based photonic applications. Biaxial (001) strain achieves mobility enhancements of 100 to 1000 with strains over 2%. Low temperature mobility can be increased by even larger factors. Second order terms in the deformation potential of the Gamma valley are found to be important in this mobility enhancement. Although they are modified by shifts in the conduction band valleys, which are caused by carrier quantum confinement, these mobility enhancements persist in strained nanostructures down to sizes of 20 nm.

(Table 1) Types of giant magnetofossils in ODP holes

Magnetotactic bacteria biomineralize magnetic minerals with precisely controlled size, morphology, and stoichiometry. These cosmopolitan bacteria are widely observed in aquatic environments. If preserved after burial, the inorganic remains of magnetotactic bacteria act as magnetofossils that record ancient geomagnetic field variations. They also have potential to provide paleoenvironmental information. In contrast to conventional magnetofossils, giant magnetofossils (most likely produced by eukaryotic organisms) have only been reported once before from Paleocene-Eocene Thermal Maximum (PETM; 55.8 Ma) sediments on the New Jersey coastal plain. Here, using transmission electron microscopic observations, we present evidence for abundant giant magnetofossils, including previously reported elongated prisms and spindles, and new giant bullet-shaped magnetite crystals, in the Southern Ocean near Antarctica, not only during the PETM, but also shortly before and after the PETM. Moreover, we have discovered giant bullet-shaped magnetite crystals from the equatorial Indian Ocean during the Mid-Eocene Climatic Optimum (~40 Ma). Our results indicate a more widespread geographic, environmental, and temporal distribution of giant magnetofossils in the geological record with a link to "hyperthermal" events. Enhanced global weathering during hyperthermals, and expanded suboxic diagenetic environments, probably provided more bioavailable iron that enabled biomineralization of giant magnetofossils. Our micromagnetic modelling indicates the presence of magnetic multi-domain (i.e., not ideal for navigation) and single domain (i.e., ideal for navigation) structures in the giant magnetite particles depending on their size, morphology and spatial arrangement. Different giant magnetite crystal morphologies appear to have had different biological functions, including magnetotaxis and other non-navigational purposes. Our observations suggest that hyperthermals provided ideal conditions for giant magnetofossils, and that these organisms were globally distributed. Much more work is needed to understand the interplay between magnetofossil morphology, climate, nutrient availability, and environmental variability.

Melt climatology estimates for small to giant Antarctic icebergs, links to NetCDF files

We present four melt climatology estimates based on a simulation of Antarctic iceberg drift and melting that includes small, medium-sized, and giant tabular icebergs with a realistic size distribution. Drift and meltdown is simulated using vertical profiles of ocean currents, temperature, and salinity, which goes beyond the present standard in iceberg modeling. The climatology estimates based on simulations of small (SMA), 'small-to-medium'-sized (MED12 & MED123), and small-to-giant icebergs (ALL) exhibit differential characteristics: successive inclusion of larger icebergs leads to a reduced seasonality of iceberg melt and a shift of the mass input to the area north of 58°S, while less melt water is released into the coastal areas. This highlights the necessity to account for larger and giant icebergs in order to obtain accurate melt climatologies. The four monthly melt climatologies [mm/day] are available as netCDF files with 1°x1° spatial resolution and can be used, e.g., for sensitivity studies with uncoupled sea ice-ocean models, or as spatio-temporal templates for the redistribution of land ice from the Antarctic ice sheet over the Southern Ocean in climate models.

Understanding arsenic mobility and speciation in lake sediments impacted by ore roasting near Giant mine, NWT

The roasting of gold-bearing arsenopyrite at Giant mine (Northwest Territories) between 1949 and 1999 released approximately 20,000 tonnes of toxic arsenic-bearing aerosols in the local aerial environment. Detailed examination of lake sediments, sediment porewaters, surface waters and lake hydrology sampled from three lakes of differing limnological characteristics was conducted in summer and winter conditions. Samples were analyzed for solid and dissolved elemental concentrations, speciation and mineralogy. The three lakes are located less than 5km from the mine roaster, and downwind, based on predominant wind direction. The objective of the study was to assess the controls on the mobility and fate of arsenic in these roaster-impacted subarctic lacustrine environments. Results show that the occurrence of arsenic trioxide in lake sediments coincides with the regional onset of industrial activities. The bulk of arsenic in sediments is contained in the form of secondary sulphide precipitates, with iron oxides hosting a minimal amount of arsenic near the surface-water interface. The presence of geogenic arsenic is likely contained as dilute impurities in common rock-forming minerals, and is not believed to be a significant source of arsenic to sediments, porewaters or lake waters. Furthermore, the well correlated depth-profiles of arsenic, antimony and gold in sediments may help reveal roaster impact. The soluble arsenic trioxide particles contained in sediments act as the primary source of arsenic into porewaters. Dissolved arsenic in reducing porewaters both precipitate as secondary sulphides in situ, and diffuse upwards into the overlying lake waters. Arsenic diffusion out of porewaters, combined with watercourse-driven residence time, are estimated to be the predominant mechanisms controlling arsenic concentrations in overlying lake waters. The sequestration of arsenic from porewaters as sulphide precipitates, in the study lakes, is not an effective process in keeping lake-water arsenic concentrations below guidelines for the protection of the freshwater environment and drinking water. Seasonal impacts on lake geochemistry derive from ice covering lake waters, cutting them off from of atmospheric oxygen, along with the exclusion of solutes from the ice. Such effects are limited in deep lakes but are can be an important factor controlling arsenic precipitation and mobility in ponds.