Biomedical subjects

Andreas Weber

Publications and source records attributed to Andreas Weber.

7 recordsLinked to original sources

PubMed2006

GADD45alpha is highly expressed in pancreatic ductal adenocarcinoma cells and required for tumor cell viability.

Pancreatic ductal adenocarcinoma is one of the most common causes of cancer death in the western civilization. Recently, NF-kappaB has been shown to be activated in pancreatic ductal adenocarcinoma through constitutive activation of IkappaB kinase (IKK). Inhibition of NF-kappaB by a super-inhibitor of NF-kappaB--delta-N-IkappaBalpha--resulted in impaired proliferation and induction of apoptosis, suggesting an important role of NF-kappaB in pancreatic tumorigenesis. Downstream target genes of IkappaBalpha have not been elucidated in pancreatic ductal adenocarcinoma in detail. Using expression profiling by cDNA array analysis of pancreatic ductal adenocarcinoma cell lines stably transfected with super-IkappaBalpha, we identified GADD45alpha as a significant regulated gene. GADD45alpha is overexpressed in pancreatic ductal adenocarcinoma at the mRNA and protein level. Using RNAi we show that downregulation of GADD45alpha reduces proliferation and induces apoptosis in pancreatic cancer cells. These findings provide evidence that GADD45alpha contributes to pancreatic cancer cell proliferation and viability.

Adenocarcinoma↗

PubMed2005

Radiological findings, pulmonary function and dyspnea in underground coal miners.

BACKGROUND: Respiratory disability induced by dust exposure in coal workers is assessed by pulmonary function tests and radiological evidence of pneumoconiosis. High-resolution computed tomography (HR-CT) improves the visibility of tissue changes, but the value of the findings for the clinical evaluation is controversial. OBJECTIVES: It was the aim of this study to evaluate the correlation between the International Labour Office (ILO) classification and the degree of emphysema in HR-CT with self-reported dyspnea and pulmonary function tests including diffusion capacity for CO (DL,CO). METHODS: We investigated 87 coal miners (aged 67+/-6 years), having worked underground for 26+/-9 years, with pulmonary function tests and HR-CT. Univariate associations were tested with correlation coefficients, and multivariable analyses used a stepwise forward regression model. RESULTS: No aspect of the ILO classification showed a univariate correlation with dyspnea or forced expiratory flow in 1 s (FEV1). Emphysema CT score was strongly associated with DL,CO (rs=-0.40; p<0.001) and FEV1/maximal vital capacity (r=-0.38; p<0.001) in univariate analysis, but not with the clinical grade of dyspnea (r=-0.14; p=0.256). CT emphysema score but not ILO classification was associated with FEV1 in multivariable analyses (rs=-0.37; p<0.001). Dyspnea was best approximated by DL,CO (r=-0.312; p=0.008). CONCLUSION: The clinical grade of breathlessness was best approximated by DL,CO. HR-CT showed a good association with expiratory flow limitation. ILO classification of the chest radiograph may be a marker of exposure but conveys little information about the degree of respiratory impairment.

Coal Mining↗

PubMed2003

The phenotype of the Arabidopsis cue1 mutant is not simply caused by a general restriction of the shikimate pathway.

The Arabidopsis thalianachlorophyll a/b binding protein underexpressed (cue1) mutant, which has been isolated in a screen for chlorophyll a/b binding protein (CAB) underexpressors, exhibits a reticulate leaf phenotype combined with delayed chloroplast development and aberrant shape of the palisade parenchyma cells. The affected gene in cue1 is a phosphoenolpyruvate (PEP)/phosphate translocator (PPT) of the plastid inner envelope membrane. The proposed function of the PPT in C3-plants is the import of PEP into the stroma as one of the substrates for the shikimate pathway, from which aromatic amino acids and a variety of secondary plant products derive. The mutant phenotype could be: (i) complemented by constitutive overexpression of a heterologous PPT from cauliflower; and (ii) rescued by overexpression of a C4-type pyruvate,orthophosphate dikinase (PPDK). The latter approach indicates that PEP deficiency within plastids triggers developmental constraints in cue1. The impact of the mutation on aspects of primary and secondary metabolism was assessed in cue1 as well as in the individual transformant lines. The majority of the data obtained in this and an accompanying paper suggest that the mutant phenotype is not simply caused by a general restriction of the shikimate pathway because of a defect in a PPT.

Arabidopsis↗

PubMed2002

Transport of carbon in non-green plastids.

Non-green plastids are important sites for the biosynthesis of starch and fatty acids, which are essential for plant development and reproduction, and have a significant role in human nutrition. Unlike chloroplasts, all the metabolites for these processes in non-green plastids have to be imported via specific transport proteins. Recent advances in unravelling the molecular structures and substrate specificities of the transporters connecting the biochemical pathways between cytosol and stroma now make it possible to develop models for metabolic fluxes in these pathways. The basic principle of adapting the transport capacities of the plastid envelope to the physiological needs of the plant is the variable production of closely related transporters with overlapping substrate specificities.

Adenosine Diphosphate Glucose↗

PubMed2002

Interaction of cytosolic and plastidic nitrogen metabolism in plants.

In angiosperms, the assimilation of ammonia resulting from nitrate reduction and from photorespiration depends on the operation of the plastidic GS/GOGAT cycle. The precursor for ammonia assimilation, 2-oxoglutarate, is synthesized in the mitochondria and in the cytosol. It is imported into the plastid by a 2-oxoglutarate/malate translocator (DiT1). In turn, the product of ammonia assimilation, glutamate, is exported from the plastids by a glutamate/malate translocator (DiT2). These transport processes link plastidic and cytosolic nitrogen metabolism and are essential for plant metabolism. DiT1 was purified to homogeneity from spinach chloroplast envelope membranes and identified as a protein with an apparent molecular mass of 45 kDa. Peptide sequences were obtained from the protein and the corresponding cDNA was cloned. The function of the DiT1 protein and its substrate specificity were confirmed by expression of the cDNA in yeast cells and functional reconstitution of the recombinant protein into liposomes. Recent advances in the molecular cloning of DiT2 and in the analysis of the in vivo function of DiT1 by antisense repression in transgenic tobacco plants will be discussed. In non-green tissues, the reducing equivalents required for glutamate formation by NADH-GOGAT are supplied by the oxidative pentose phosphate pathway. Glucose 6-phosphate, the immediate precursor of the oxidative pentose phosphate pathway is generated in the cytosol and imported into the plastids by the plastidic glucose 6-phosphate/phosphate translocator.

Amino Acid Oxidoreductases↗

PubMed2002

The rolB-like part of the Agrobacterium rhizogenes orf8 gene inhibits sucrose export in tobacco.

Many Agrobacterium T-DNA genes belong to the highly diverse rolB family. The mode of action of most of these genes is still unknown. rolB-like sequences also are present at the 5' ends of the T-DNA-located iaaM genes and the iaaM homolog orf8, whereas iaaM genes from Pseudomonas and Erwinia spp. lack such sequences. iaaM genes encode tryptophan monooxygenases; these enzymes convert tryptophan into indole-3-acetamide, a precursor of indole-3-acetic acid. Tobacco plants expressing the rolB-like part of the A4 orf8 gene (2x35S-A4-Norf8 plants) accumulate glucose, fructose, sucrose, and starch and resemble sucrose transporter (NtSUT1) antisense plants. Different lines of evidence indicate that 2x35S-A4-Norf8 plants export less sucrose from source leaves. Glucose, fructose, sucrose, and starch accumulate in source leaves during sink-source transition, whereas sink tissues like petioles and midveins contain lower levels than normal. Petiole exudation experiments demonstrate a significant decrease in export of label after 14C-sucrose infiltration and after 14CO2 labeling. Grafting of stunted homozygous 2x35S-A4-Norf8 plants onto wild-type rootstocks restores growth, indicating that unloading is not affected. Growth of 2x35S-A4-Norf8 seedlings is inhibited on naphthalene acetic acid-containing media, suggesting a link between sucrose transport and auxin sensitivity.

Bacterial Proteins↗

PubMedDate not supplied

Light scattering from filaments.

Photo realistic visualization of a huge number of individual filaments like in the case of hair, fur, or knitwear is a challenging task: Explicit rendering approaches for simulating radiance transfer at a filament get totally impracticable with respect to rendering performance and it is also not obvious how to derive efficient scattering functions for different levels of (geometric) abstraction or how to deal with very complex scattering mechanisms. We present a novel uniform formalism for light scattering from filaments in terms of radiance, which we call the Bidirectional Fiber Scattering Distribution Function (BFSDF). We show that previous specialized approaches, which have been developed in the context of hair rendering, can be seen as instances of the BFSDF. Similar to the role of the BSSRDF for surface scattering functions, the BFSDF can be seen as a general approach for light scattering from filaments, which is suitable for deriving approximations in a canonic and systematic way. For the frequent cases of distant light sources and observers, we deduce an efficient far field approximation (Bidirectional Curve Scattering Distribution Function, BCSDF). We show that on the basis of the BFSDF, parameters for common rendering techniques can be estimated in a non-ad-hoc, but physically-based way.

Algorithms↗