Crystal size and oxygen segregation for polycrystalline GaN

The grain size for polycrystallineGaN,grown in low-temperature gallium-rich conditions, is shown to be correlated to the oxygen content of the films. Films with lower oxygen content were observed to have larger crystals with an increased tendency to a single-preferred crystal orientation.Elastic recoil detection analysis with heavy ions (i.e., 200 MeV ¹⁹⁷Au ions) was used to determine the composition of the GaN films grown for the study, including the hydrogen, carbon, gallium, nitrogen, and oxygen content. Atomic force microscopy and x-ray diffraction were used to study the sample morphology. From these measurements, the available surface area of the films was found to be sufficient for a significant proportion of the oxygen present in the films to segregate at the grain boundaries. This interpretation is consistent with earlier theoretical studies of the formation and segregation of the VGa-(ON)₃defect complex at dislocation sites in gallium-rich GaN. For this work, however, the defect complex is believed to segregate at the grain boundary of the polycrystallineGaN.The authors would like to acknowledge the support of a U. S. NICOP Contract, No. N00014-99-1-GO17 sponsored through the U. S. Office of Naval Research. One of the authors (K.S.A.B.) would like to further acknowledge the support of a Macquarie University Research Fellowship

A combinatorial TIR1/AFB–Aux/IAA co-receptor system for differential sensing of auxin

The plant hormone auxin regulates virtually every aspect of plant growth and development. Auxin acts by binding the F-box protein transport inhibitor response 1 (TIR1) and promotes the degradation of the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressors. Here we show that efficient auxin binding requires assembly of an auxin co-receptor complex consisting of TIR1 and an Aux/IAA protein. Heterologous experiments in yeast and quantitative IAA binding assays using purified proteins showed that different combinations of TIR1 and Aux/IAA proteins form co-receptor complexes with a wide range of auxin-binding affinities. Auxin affinity seems to be largely determined by the Aux/IAA. As there are 6 TIR1/AUXIN SIGNALING F-BOX proteins (AFBs) and 29 Aux/IAA proteins in Arabidopsis thaliana, combinatorial interactions may result in many co-receptors with distinct auxin-sensing properties. We also demonstrate that the AFB5–Aux/IAA co-receptor selectively binds the auxinic herbicide picloram. This co-receptor system broadens the effective concentration range of the hormone and may contribute to the complexity of auxin response

Foot pressure distribution during walking in young and old adults

BACKGROUND: Measurement of foot pressure distribution (FPD) is clinically useful for evaluation of foot and gait pathologies. The effects of healthy aging on FPD during walking are not well known. This study evaluated FPD during normal walking in healthy young and elderly subjects. METHODS: We studied 9 young (30 ± 5.2 years), and 6 elderly subjects (68.7 ± 4.8 years). FPD was measured during normal walking speed using shoe insoles with 99 capacitive sensors. Measured parameters included gait phase characteristics, mean and maximum pressure and force, and relative load. Time-series measurements of each variable for all sensors were grouped into 9 anatomical masks. RESULTS: Elderly subjects had lower normalized maximum pressure for the medial and lateral calcaneal masks, and for all medial masks combined. In the medial calcaneus mask, the elderly group also had a lower absolute maximum and lower mean and normalized mean pressures and forces, compared to young subjects. Elderly subjects had lower maximum force and normalized maximum force and lower mean force and normalized mean forces in the medial masks as well. CONCLUSION: FPD differences between the young and elderly groups were confined to the calcaneus and hallux regions and to the medial side of the foot. In elderly subjects, weight bearing on the lateral side of the foot during heel touch and toe-off phases may affect stability during walking

Three-dimensional structure of β-cell-specific zinc transporter, ZnT-8, predicted from the type 2 diabetes-associated gene variant SLC30A8 R325W

<p>Abstract</p> <p>Background</p> <p>We examined the effects of the R325W mutation on the three-dimensional (3D) structure of the β-cell-specific Zn²⁺(zinc) transporter ZnT-8.</p> <p>Methods</p> <p>A model of the C-terminal domain of the human ZnT-8 protein was generated by homology modeling based on the known crystal structure of the <it>Escherichia coli </it>(<it>E. coli</it>) zinc transporter YiiP at 3.8 Å resolution.</p> <p>Results</p> <p>The homodimer ZnT-8 protein structure exists as a Y-shaped architecture with Arg325 located at the ultimate bottom of this motif at approximately 13.5 Å from the transmembrane domain juncture. The C-terminal domain sequences of the human ZnT-8 protein and the <it>E. coli </it>zinc transporter YiiP share 12.3% identical and 39.5% homologous residues resulting in an overall homology of 51.8%. Validation statistics of the homology model showed a reasonable quality of the model. The C-terminal domain exhibited an αββαβ fold with Arg325 as the penultimate N-terminal residue of the α2-helix. The side chains of both Arg325 and Trp325 point away from the interface with the other monomer, whereas the ε-NH₃⁺group of Arg325 is predicted to form an ionic interaction with the β-COO^-group of Asp326 as well as Asp295. An amino acid alignment of the β2-α2 C-terminal loop domain revealed a variety of neutral amino acids at position 325 of different ZnT-8 proteins.</p> <p>Conclusions</p> <p>Our validated homology models predict that both Arg325 and Trp325, amino acids with a helix-forming behavior, and penultimate N-terminal residues in the α2-helix of the C-terminal domain, are shielded by the planar surface of the three cytoplasmic β-strands and hence unable to affect the sensing capacity of the C-terminal domain. Moreover, the amino acid residue at position 325 is too far removed from the docking and transporter parts of ZnT-8 to affect their local protein conformations. These data indicate that the inherited R325W abnormality in SLC30A8 may be tolerated and results in adequate zinc transfer to the correct sites in the pancreatic islet cells and are consistent with the observation that the <it>SLC30A8 </it>gene variant R325W has a low predicted value for future type 2 diabetes at population-based level.</p

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors:Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure

Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?

Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic cells and by its IGF-1 related properties. However, insulin-stimulated angiogenesis could be an additional factor involved in tumour progression and clinical outcomes associated with cancer. Five types of human adenocarcinoma (breast, colon, pancreas, lung and kidney) were evaluated for the presence of insulin receptors (IRs) on angiogenic structures. In an in vitro angiogenesis assay, various commercially available insulin compounds were evaluated for their potential to increase capillary-like tube formation of human microvascular endothelial cells (hMVEC). Insulin compounds used were: human insulin, insulin lispro (B28Lys,B29Pro human insulin), insulin glargine and insulin detemir (B29Lys[e-tetradecanoyl],desB30 human insulin). Insulin receptors were found to be strongly expressed on the endothelium of microvessels in all evaluated adenocarcinomas, in addition to variable expression on tumour cells. Low or no detectable expression of IRs was seen on microvessels in extratumoral stroma. Incubation with commercially available insulin compounds increased capillary-like tube formation of hMVEC in vitro. Our results suggest that all tested insulin compounds may stimulate tumour growth by enhancing local angiogenesis. Future studies need to confirm the association between insulin therapy in type 2 diabetes and tumour progressio

Echocardiography protocol for early detection of cardiac dysfunction in childhood cancer survivors in the multicenter DCCSS LATER 2 CARD study:Design, feasibility, and reproducibility

Background Cardiotoxicity is a well-known side effect after anthracyclines and chest radiotherapy in childhood cancer survivors (CCS). The DCCSS LATER 2 CARD (cardiology) study includes evaluation of echocardiographic measurements for early identification of CCS at highest risk of developing heart failure. This paper describes the design, feasibility, and reproducibility of the echocardiography protocol. Methods Echocardiograms from CCS and sibling controls were prospectively obtained at the participating centers and centrally analyzed. We describe the image acquisition, measurement protocol, and software-specific considerations for myocardial strain analyses. We report the feasibility of the primary outcomes of systolic and diastolic function, as well as reproducibility analyses in 30 subjects. Results We obtained 1,679 echocardiograms. Biplane ejection fraction (LVEF) measurement was feasible in 91% and 96% of CCS and siblings, respectively, global longitudinal strain (GLS) in 80% and 91%, global circumferential strain (GCS) in 86% and 89%, and >= 2 diastolic function parameters in 99% and 100%, right ventricle free wall strain (RVFWS) in 57% and 65%, and left atrial reservoir strain (LASr) in 72% and 79%. Intra-class correlation coefficients for inter-observer variability were 0.85 for LVEF, 0.76 for GLS, 0.70 for GCS, 0.89 for RVFWS and 0.89 for LASr. Intra-class correlation coefficients for intra-observer variability were 0.87 for LVEF, 0.82 for GLS, 0.82 for GCS, 0.85 for RVFWS and 0.79 for LASr. Conclusion The DCCSS LATER 2 CARD study includes a protocolized echocardiogram, with feasible and reproducible primary outcome measurements. This ensures high-quality outcome data for prevalence estimates and for reliable comparison of cardiac function parameters

Genes of Both Parental Origins Are Differentially Involved in Early Embryogenesis of a Tobacco Interspecies Hybrid

BACKGROUND: In animals, early embryonic development is largely dependent on maternal transcripts synthesized during gametogenesis. However, in higher plants, the extent of maternal control over zygote development and early embryogenesis is not fully understood yet. Nothing is known about the activity of the parental genomes during seed formation of interspecies hybrids. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that an interspecies hybridization system between SR1 (Nicotiana tabacum) and Hamayan (N. rustica) has been successfully established. Based on the system we selected 58 genes that have polymorphic sites between SR1 and Hamayan, and analyzed the allele-specific expression of 28 genes in their hybrid zygotes (Hamayan x SR1). Finally the allele-specific expressions of 8 genes in hybrid zygotes were repeatedly confirmed. Among them, 4 genes were of paternal origin, 1 gene was of maternal origin and 3 genes were of biparental origin. These results revealed obvious biparental involvement and differentially contribution of parental-origin genes to zygote development in the interspecies hybrid. We further detected the expression pattern of the genes at 8-celled embryo stage found that the involvement of the parental-origin genes may change at different stages of embryogenesis. CONCLUSIONS/SIGNIFICANCE: We reveal that genes of both parental origins are differentially involved in early embryogenesis of a tobacco interspecies hybrid and functions in a developmental stage-dependent manner. This finding may open a window to seek for the possible molecular mechanism of hybrid vigor