Mutations in cardiac T-Box Factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.

Industrial land price and its impact on urban growth : a Chinese case study

China is experiencing rapid progress in industrialization, with its own rationale toward industrial land development based on a deliberate change from an extensive to intensive form of urban land use. One result has been concerted attempts by local government to attract foreign investment by a low industrial land price strategy, which has resulted in a disproportionally large amount of industrial land within the total urban land use structure at the expense of the urban sprawl of many cities. This paper first examines “Comparable Benchmark Price as Residential land use” (CBPR) as the theoretical basis of the low industrial land price phenomenon. Empirical findings are presented from a case study based on data from Jinyun County, China. These data are analyzed to reveal the rationale of industrial land price from 2000 to 2010 concerning the CBPR model. We then explore the causes of low industrial land prices in the form of a “Centipede Game Model”, involving two neighborhood regions as “major players” to make a set of moves (or strategies). When one of the players unilaterally reduces the land price to attract investment with the aim to maximize profits arising from the revenues generated from foreign investment and land premiums, a two-player price war begins in the form of a dynamic game, the effect of which is to produce a downward spiral of prices. In this context, the paradox of maximizing profits for each of the two players are not accomplished due to the inter-regional competition of attracted investment leading to a lose-lose situation for both sides’ in competing for land premium revenues. A short-term solution to the problem is offered involving the establishment of inter-regional cooperative partnerships. For the longer term, however, a comprehensive reform of the local financial system, more adroit regional planning and an improved means of evaluating government performance is needed to ensure the government's role in securing pubic goods is not abandoned in favor of one solely concerned with revenue generation.

Capturing gazelles : features of high potential firms and new venture growth

This paper investigates the characteristics of ventures which have the potential to reach high growth and compares this with ‘everyday’ new ventures. Findings of interest in this paper include: • HP firms are characterised by higher human capital, are more likely to have a team of founders, are more likely to be product based. • HP firms are more likely to achieve more extreme levels of growth (both positive and negative). • HP ventures that make a loss are more likely to do so early in the venture process. Those that do hold on show that there can higher levels of loss made later on in firm development. HP firms have higher resource needs, in terms of seeking external finance, but are no more likely to receive external finance than regular firms.

Postdiagnosis personal growth in an Australian population of parents raising children with developmental disability

Background Parenting a child with a developmental disability presents a variety of long-term physical and emotional challenges. When exploring parent wellbeing, the disability field is dominated by a deficit model despite parents reportedly demonstrating coping and resilience. The current study is embedded in a salutogenic theory (Antonovsky, 1979) and explores the potential for parents of children diagnosed with a developmental disability to undergo positive changes. Method Participants were 6 fathers and 27 mothers who completed measures of distress and posttraumatic growth. Results Compared with a number of other Australian samples, participants reported significantly higher levels of posttraumatic growth. Reports of growth did not negate reports of distress. Results also indicated that constructs of distress and growth were independent. Conclusions The research has important implications for disability support services, reminding providers to be cognisant of the potential for growth, as well as distress, thereby permitting an atmosphere conducive to exploring such outcomes.

Phenotypic changes in artemisinin-resistant plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition

The appearance of Plasmodium falciparum parasites with decreased in vivo sensitivity but no measurable in vitro resistance to artemisinin has raised the urgent need to characterize the artemisinin resistance phenotype. Changes in the temporary growth arrest (dormancy) profile of parasites may be one aspect of this phenotype. In this study, we investigated the link between dormancy and resistance, using artelinic acid (AL)-resistant parasites. Our results demonstrate that the AL resistance phenotype has (i) decreased sensitivity of mature-stage parasites, (ii) decreased sensitivity of the ring stage to the induction of dormancy, and (iii) a faster recovery from dormancy.

Entrepreneurial growth : the role of international knowledge acquisition as moderated by firm age

In line with repeated recent calls for research on specific forms of growth rather than on an undifferentiated notion of “total growth,” our study contributes to the understanding of entrepreneurial growth. By this we mean growth through expansion into new geographic markets and/or via the introduction of new products or services. Building on Penrose's theory of the growth of the firm and on the research streams she has in part inspired, we investigate the impact of knowledge acquisition from international markets on entrepreneurial growth both at home and abroad. We further suggest that the effects of international knowledge acquisition on entrepreneurial growth will vary with firm age. Utilizing longitudinal data on 138 small and medium-sized enterprises (SMEs), we find that the acquisition of knowledge from international markets fuels growth through market development, and that this effect is stronger for international expansion than domestic expansion. Our results also show that firm age negatively moderates the relationship between international knowledge acquisition and entrepreneurial growth via the introduction of new products or services. Specifically, international knowledge acquisition has a positive effect on growth via new products/services development in young firms, but a negative effect in mature firms. We assume this reflects changes over time in how international knowledge is managed.

Molecular genetic analyses of RFLPs for PCR-amplified growth hormone gene, renal kallikrein gene and atrial natriuretic factor gene in essential hypertension

The present study examined polymorphisms of genes that might be involved in the onset of essential hypertension (HT). These included the (i) growth hormone gene (GH1), whose locus has recently been linked to elevated blood pressure (BP) in the stroke-prone SHR, although recent sib-pair analysis of a polymorphism near the human chorionic somatomammotropin gene (a member of the GH cluster) was unable to show linkage with HT; (ii) renal kallikrein gene (KLK1); and (iii) atrial natriuretic factor gene (ANF), where a primary defect in production or activity of kallikrein or ANF could cause NaCl retention and vasoconstriction. Association analyses were conducted to compare restriction fragment length polymorphisms (RFLPs) of each gene in 85 HT and 95 normotensive (NT) Caucasian subjects whose parents had a similar BP status at age ≥50 years. The frequency of the minor allele of (i) a RsaI RFLP in the promoter of GH1, amplified from leukocyte DNA by the polymerase chain reaction, was 0.15 in the HT group and 0.14 in the NT group (χ1=0.34, P=0.55); (ii) a TaqI RFLP for KLK1 was 0.035 in the HT group and 0.015 in the NT group (χ2=1.5, P=0.21); and (iii) a XhoI RFLP for ANF was 0.50 in HTs and 0.46 in NTs (χ2=0.20, P=0.65). Studies of HT pedigrees found one family in which the ANF locus and HT were not linked, owing to an obligate recombinant. The present data thus provide no evidence for involvement of the growth hormone, renal kallikrein, nor ANF gene in the causation of essential hypertension.

Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse

Reasons for performing the study As growth hormone increases lean body mass, it could be a therapy for obese horses. However, growth hormone use induces hyperinsulinaemia in some species, so further investigation is warranted. Objectives To investigate the effects of feeding, exercise and growth hormone therapy on basal insulin concentrations in healthy horses. Study design In vivo experimental study. Methods Blood samples were obtained every 30 min from 12 geldings over 24 h, to establish basal serum insulin concentrations, before they underwent a 3-week exercise programme. Horses were allocated into 2 groups and exercised for another 4 weeks. Group A received daily i.m. injections of recombinant equine growth hormone; 5 mg/day for 5 days, then 12.5 mg/day for 16 days. Blood samples were taken daily before feeding. Insulin vs. time area under curve of Groups A and B were compared using a Student's unpaired t test. Results Horses demonstrated insulin peaks within 2 h of feeding of 577 ± 108.3 pmol/l at 09.30 h and 342.4 ± 75.7 pmol/l at 17.30 h, despite receiving the same meal. The nadir was between midnight and 07.30 h. Exercise had no effect on basal insulin concentrations prior to equine growth hormone administrations. The equine growth hormone injections increased serum insulin concentrations (P = 0.01) within Group A, from 44.4 ± 15.3 pmol/l initially to 320.9 ± 238.2 pmol/l by Day 12. Exogenous growth hormone caused variable hyperinsulinaemia, which was alleviated once equine growth hormone administration ceased. Conclusions Single serum samples taken prior to the morning meal provide basal insulin concentrations. Exercise did not change basal insulin concentrations. However, equine growth hormone injections increased basal insulin concentrations, which were not ameliorated by exercise. Potential relevance This therapy is not recommended to address obesity in insulin-resistant equids.

Converse consumption : the converse blank canvas project

Research background For almost 80 years the Chuck Taylor (or Chuck T's) All Star basketball shoe has been an iconic item of fashion apparel. The Chuck T's were first designed in 1921 by Converse, an American shoe company and over the decades they became a popular item not purely for sports and athletic purposes but rather evolved into the shoe of choice for many subcultural groups as a fashion item. In some circles the Chuck Taylor is still seen as the "coolest" sneaker of all time - one which will never go out of fashion regardless of changing trends. With over 600 millions pairs sold all over the world since its release, the Converse shoe is representative of not only a fashion culture - but also of a consumption culture - that evolved as the driving force behind the massive growth of the Western economic system during the 20th Century. Artisan Gallery (Brisbane), in conjunction with the exhibition Reboot: Function, Fashion and the Sneaker, a history of the sneaker, selected 20 designers to customise and re-design the classic Converse Chuck Taylor All Stars shoe and in doing so highlighted the diversity of forms possible for creative outcomes. As Artisan Gallery Curator Kirsten Fitzpatrick states “We were expecting people to draw and paint on them. Instead, we had shoes... mounted as trophies.." referring to the presentation of "Converse Consumption". The exhibition ran from 21 June – 16 August 2012: Research question The Chuck T’s is one of many overwhelmingly commercially successful designs of the last century. Nowadays we are faced with the significant problems of overconsumption and the stress this causes on the natural ecosystem; and on people as a result. As an active member of the industrial design fraternity – a discipline that sits at the core of this problem - how can I use this opportunity to comment on the significant issue of consumption? An effective way to do this was to associate consumption of goods with consumption of sugar. There are significant similarities between our ceaseless desires to consume products and our fervent need to consume indulgent sweet foods. Artisan Statement Delicious, scrumptious, delectable... your pupils dilate, your blood pressure spikes, your liver goes into overdrive. Immediately, your brain cuts off the adenosine receptors, preventing drowsiness. Your body increases dopamine production, in-turn stimulating the pleasure receptors in your brain. Your body absorbs all the sweetness and turns it into fat – while all the nutrients that you actually require are starting to be destroyed, about to be expelled. And this is only after one bite! After some time though, your body comes crashing back to earth. You become irritable and begin to feel sluggish. Your eyelids seem heavy while your breathing pattern changes. Your body has consumed all the energy and destroyed all available nutrients. You literally begin to shut down. These are the physiological effects of sugar consumption. A perfect analogy for our modern day consumer driven world. Enjoy your dessert! Research contribution “Converse Consumption” contributes to the conversation regarding over-consumption by compelling people to reflect on their consumption behaviour through the reconceptualising of the deconstructed Chuck T’s in an attractive edible form. By doing so the viewer has to deal with the desire to consume the indulgent looking dessert with the contradictory fact that it is comprised of a pair of shoes. The fact that the shoes are Chuck T’s make the effect even more powerful due to their iconic status. These clashing motivations are what make “Converse Consumption” a bizarre yet memorable experience. Significance The exhibition was viewed by an excess of 1000 people and generated exceptional media coverage and public exposure/impact. As Artisan Gallery Curator Kirsten Fitzpatrick states “20 of Brisbane's best designers were given the opportunity to customise their own Converse Sneakers, with The Converse Blank Canvas Project.” And to be selected in this category demonstrates the calibre of importance for design prominence.

A meta-analytic clarification of the relationship between posttraumatic growth and symptoms of posttraumatic distress disorder

Traumatic experiences can have a powerful impact on individuals and communities but the relationship between perceptions of beneficial and pathological outcomes are not known. Therefore, this meta-analysis examined both the strength and the linearity of the relationship between symptoms of posttraumatic stress disorder (PTSD) and perceptions of posttraumatic growth (PTG) as well as identifying the potential moderating roles of trauma type and age. Literature searches of all languages were conducted using the ProQuest, Wiley Interscience, ScienceDirect, Informaworld and Web of Science databases. Linear and quadratic (curvilinear) rs as well as βs were analysed. Forty-two studies (N=11, 469) that examined both PTG and symptoms of PTSD were included in meta-analytic calculations. The combined studies yielded a significant linear relationship between PTG and PTSD symptoms (r=.315, CI = 0.299, 0.331), but also a significantly stronger (as tested by Fisher’s transformation) curvilinear relationship (r=.372, CI = 0.353, 0.391). The strength and linearity of these relationships differed according to trauma type and age. The results remind those working with traumatised people that positive and negative post-trauma outcomes can co-occur. A focus only on PTSD symptoms only may limit or slow recovery and mask the potential for growth.

Controls on mid-Holocene fringing reef growth and termination in a high latitude, estuarine setting, Wellington Point, Southeast Queensland

Several fringing coral reefs in Moreton Bay, Southeast Queensland, some 300 km south of the Great Barrier Reef (GBR), are set in a relatively high latitude, estuarine environment that is considered marginal for coral growth. Previous work indicated that these marginal reefs, as with many fringing reefs of the inner GBR, ceased accreting in the mid-Holocene. This research presents for the first time data from the subsurface profile of the mid-Holocene fossil reef at Wellington Point comprising U/Th dates of in situ and framework corals, and trace element analysis from the age constrained carbonate fragments. Based on trace element proxies the palaeo-water quality during reef accretion was reconstructed. Results demonstrate that the reef initiated more than 7,000 yr BP during the post glacial transgression, and the initiation progressed to the west as sea level rose. In situ micro-atolls indicate that sea level was at least 1 m above present mean sea level by 6,680 years ago. The reef remained in "catch-up" mode, with a seaward sloping upper surface, until it stopped aggrading abruptly at ca 6,000 yr BP; no lateral progradation occurred. Changes in sediment composition encountered in the cores suggest that after the laterite substrate was covered by the reef, most of the sediment was produced by the carbonate factory with minimal terrigenous influence. Rare earth element, Y and Ba proxies indicate that water quality during reef accretion was similar to oceanic waters, considered suitable for coral growth. A slight decline in water quality on the basis of increased Ba in the later stages of growth may be related to increased riverine input and partial closing up of the bay due to either tidal delta progradation, climatic change and/or slight sea level fall. The age data suggest that termination of reef growth coincided with a slight lowering of sea level, activation of ENSO and consequent increase in seasonality, lowering of temperatures and the constrictions to oceanic flushing. At the cessation of reef accretion the environmental conditions in the western Moreton Bay were changing from open marine to estuarine. The living coral community appears to be similar to the fossil community, but without the branching Acropora spp. that were more common in the fossil reef. In this marginal setting coral growth periods do not always correspond to periods of reef accretion due to insufficient coral abundance. Due to several environmental constraints modern coral growth is insufficient for reef growth. Based on these findings Moreton Bay may be unsuitable as a long term coral refuge for most species currently living in the GBR.

YBCO thin films on Yttria stabilized Zirconia and LaAlO3-growth and properties

Laser deposition was used to deposit YBaCuO thin films on Yttria-stabilized Zirconia substrates, at substrate holder temperatures of 710-765 °C. We observed a transition from singlecrystalline to polycrystalline growth at a temperature of ∼750 °C. All films were highly c-axis oriented and had critical temperatures between 89.5 and 92 K. In the twinned singlecrystalline films, the lowest measured microwave surface resistance was 0.37 mΩ at 4.2 K and 21.5 GHz, and the highest critical current 5×106 A/cm2 at 77 K. The polycrystalline films had up to a factor of 50 higher surface resistance and a factor of 10 lower critical current. A meander line resonator made of a film on a LaAlO3 substrate, showed a microwave surface resistance of 5μΩ at 4.2 K and 2.5 GHz. © 1991.

Early stages of growth of YBa2Cu3O7-δ high Tc superconducting films on (001) Y-ZrO2 substrates

The early stages of growth of high quality YBa2Cu 3O7-δ (YBCO) films grown on (001) Y-ZrO2 (YSZ) substrates by pulsed laser deposition have been studied using a combination of atomic force microscopy and transmission electron microscopy. A one unit cell thick YBCO layer and relatively large CuO particles formed in the initial stages. Additional YBCO grew on top of the first layer in the form of one or a few unit cell high c-axis oriented islands about 30 nm in diameter. The rounded islands subsequently coalesced into faceted domains. Elongated Y 2BaCuO5 particles nucleated after the first layer of YBCO. A highly textured BaZrO3 layer formed between the YSZ and the YBCO with a cube-on-cube dominant orientation relationship with respect to the YBCO film.

Growth and properties of a multilayer system based on Y1Ba 2Cu3Ox and amorphous Y-ZrO2

The growth of c-axis oriented Y1Ba2Cu 3Ox thin films on an amorphous buffer layer of Y-ZrO 2, deposited on sapphire substrates, was investigated. Both films were grown by a pulsed laser deposition technique. A strong correlation was observed between the properties of Y1Ba2Cu 3Ox and the thickness of the buffer layer. A Tc of 89 K was obtained for an optimal buffer layer thickness of 9 nm. A model that adequately describes the film growth process was developed. A multilayer system of Y1Ba2Cu3Ox and amorphous Y-ZrO2 was grown and a Tc of 87 K for the upper c-axis oriented layer was measured.