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Biomedical subjects

Jörg Hofmann

Publications and source records attributed to Jörg Hofmann.

10 recordsLinked to original sources
PubMed2006

Defoliation and plasmid delivery with layer-by-layer coated colloids.

The uptake of polyelectrolyte multilayer coated colloids into cells, subsequent defoliation and plasmid delivery was studied by means of confocal microscopy and flow cytometry. Silica particles coated layer-wise with protamine and dextran sulfate were given to HEK 293T cells. Optimum uptake was found with protamine as the top layer. The particle uptake likely follows an non-receptor-mediated endocytotic pathway. Defoliation of polyelectrolyte multilayer coated particles within cells was demonstrated by the release of incorporated plasmids as indicated by the expression of plasmid encoded proteins using the enhanced green fluorescence proteine (pEGFP-C1) plasmid and a red fluorescence protein (pDsRed1-N1) plasmid. This proves, together with the direct observation of fluorescent layer debris, the defoliation of coated particles and the release of layer components into the cytoplasm. Particle uptake and GFP expression.

Animals↗
PubMed2006

Analysis of the transmission of Salmonella spp. through generations of pet snakes.

Besides the 'classical' animals known as reservoirs for Salmonella spp., like poultry and cattle, reptiles have emerged as a significant source of human salmonellae infections during the last years. Reptile-associated salmonellae frequently cause severe clinical courses including fatalities due to septicaemia and meningitis. Therefore, it is of major priority to develop measures which may help preventing cases of reptile-associated salmonellae. However, as a first step the epidemiology of salmonellae in reptiles must be understood. Therefore, in this study a population analysis of the salmonellae of two female snakes was performed and the pattern of inheritance of salmonellae to their offspring was investigated. It is demonstrated that adult snakes usually harbour a population of concurrent salmonellae serovars. Colonization of their offspring during pregnancy and birth is a significant way of transmission causing 65% of the newborn to be positive for salmonellae. The effectiveness of the transmission does not seem to be due only to the frequency of a certain serovar, because the most prevailing strain of one female snake was not detectable in any of her offspring.

Animals↗
PubMed2005

Acoustic cavitation induced by ultrasonic cutting devices: a preliminary study.

Ultrasonic cutting is frequently used for the separation of foods, especially in case of commodities with multiple layers showing a different mechanical resistance. Both chemiluminescence measurements and the degradation of organochloric compounds served as an evidence for the occurrence of acoustic cavitation around excited cutting blades. Additionally, sensory experiments revealed that even a short ultrasonic treatment of edible oil is sufficient to generate a remarkable off-flavor.

Journal Article↗
PubMed2005

Cloning, expression, and characterization of the human mitochondrial beta-ketoacyl synthase. Complementation of the yeast CEM1 knock-out strain.

A human beta-ketoacyl synthase implicated in a mitochondrial pathway for fatty acid synthesis has been identified, cloned, expressed, and characterized. Sequence analysis indicates that the protein is more closely related to freestanding counterparts found in prokaryotes and chloroplasts than it is to the beta-ketoacyl synthase domain of the human cytosolic fatty acid synthase. The full-length nuclear-encoded 459-residue protein includes an N-terminal sequence element of approximately 38 residues that functions as a mitochondrial targeting sequence. The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein and is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels. To date, four components of a putative type II mitochondrial fatty acid synthase pathway have been identified in humans: acyl carrier protein, malonyl transferase, beta-ketoacyl synthase, and enoyl reductase. The substrate specificity and complementation data for the beta-ketoacyl synthase suggest that, as in plants and fungi, in humans this pathway may play an important role in the generation of octanoyl-acyl carrier protein, the lipoic acid precursor, as well as longer chain fatty acids that are required for optimal mitochondrial function.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed2004

HFA1 encoding an organelle-specific acetyl-CoA carboxylase controls mitochondrial fatty acid synthesis in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae gene, HFA1, encodes a >250-kDa protein, which is required for mitochondrial function. Hfa1p exhibits 72% overall sequence similarity (54% identity) to ACC1-encoded yeast cytoplasmic acetyl-CoA carboxylase. Nevertheless, HFA1 and ACC1 functions are not overlapping because mutants of the two genes have different phenotypes and do not complement each other. Whereas ACC1 is involved in cytoplasmic fatty acid synthesis, the phenotype of hfa1Delta disruptants resembles that of mitochondrial fatty-acid synthase mutants. They fail to grow on lactate or glycerol, and the mitochondrial cofactor, lipoic acid, is reduced to <10% of its normal cellular concentration. Other than Acc1p, the N-terminal sequence of Hfa1p comprises a canonical mitochondrial targeting signal together with a matrix protease cleavage site. Accordingly, the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment. Removal of the mitochondrial targeting sequence abolished the competence of HFA1 DNA to complement hfal null mutants. Conversely and in contrast to the intact HFA1 sequence, the signal sequence-free HFA1 gene complemented the mutational loss of cytoplasmic acetyl-CoA carboxylase. Expression of HFA1 under the control of the ACC1 promoter restored cellular ACC activity in ACC1-defective yeast mutants to wild type levels. From this finding, it is concluded that HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis.

Acetyl-CoA Carboxylase↗
PubMed2004

Microbial type I fatty acid synthases (FAS): major players in a network of cellular FAS systems.

The present review focuses on microbial type I fatty acid synthases (FASs), demonstrating their structural and functional diversity. Depending on their origin and biochemical function, multifunctional type I FAS proteins form dimers or hexamers with characteristic organization of their catalytic domains. A single polypeptide may contain one or more sets of the eight FAS component functions. Alternatively, these functions may split up into two different and mutually complementing subunits. Targeted inactivation of the individual yeast FAS acylation sites allowed us to define their roles during the overall catalytic process. In particular, their pronounced negative cooperativity is presumed to coordinate the FAS initiation and chain elongation reactions. Expression of the unlinked genes, FAS1 and FAS2, is in part constitutive and in part subject to repression by the phospholipid precursors inositol and choline. The interplay of the involved regulatory proteins, Rap1, Reb1, Abf1, Ino2/Ino4, Opi1, Sin3 and TFIIB, has been elucidated in considerable detail. Balanced levels of subunits alpha and beta are ensured by an autoregulatory effect of FAS1 on FAS2 expression and by posttranslational degradation of excess FAS subunits. The functional specificity of type I FAS multienzymes usually requires the presence of multiple FAS systems within the same cell. De novo synthesis of long-chain fatty acids, mitochondrial fatty acid synthesis, acylation of certain secondary metabolites and coenzymes, fatty acid elongation, and the vast diversity of mycobacterial lipids each result from specific FAS activities. The microcompartmentalization of FAS activities in type I multienzymes may thus allow for both the controlled and concerted action of multiple FAS systems within the same cell.

Corynebacterium↗
PubMed2004

Concentrations of N-terminal pro-brain natriuretic peptide and troponin T in plasma of 75-year-old apparently healthy persons.

Clinical chemical reference values for older persons are sparse and mostly intermixed with those for younger persons. We had a unique opportunity to obtain blood samples from volunteers who were 75 years old and living in two districts of Vienna, Austria. Consequently, we utilized stored plasma samples to obtain reference intervals for 120 apparently healthy 75-year-old participants for pro-brain natriuretic peptide (proBNP), as well as for troponin T. The N-terminal (NT)-proBNP protein assay is currently used as a diagnostic and prognostic aid in patients with heart failure and as a prognostic marker in acute coronary syndromes. Specifically, the concentration of NT-proBNP in serum or plasma aids in the prognosis of ventricular systolic dysfunction and helps to differentiate between cardiac and non-cardiac causes. The median NT-proBNP plasma value for men and women in our cohort was calculated as 98 pg/ml, comparing favorably with reported values, in that a NT-proBNP concentration less than 100 pg/ml excludes acutely decompensated heart failure. Our calculated 97.5 percentile was slightly higher (359 pg/ml) than the 97.5 percentile in a group of 50-65-year-old persons (198 and 222 pg/ml for men and women, respectively) revealing the influence of age on this parameter. Because of its high tissue-specificity, cardiac troponin T is a cardiospecific, highly sensitive marker for myocardial damage. However, the troponin T concentrations in the plasma specimens from this cohort were all below the detection limit of 0.01 ng/ml, preventing any further data handling.

Aged↗
PubMed2003

Ultrasound promoted C-alkylation of benzyl cyanide--effect of reactor and ultrasound parameters.

Phase transfer catalysis is used widely in the synthesis of various organic chemicals in both liquid-liquid and solid-liquid systems. The C-alkylation of benzyl cyanide by 2-bromopropane in the presence of sodium hydroxide was investigated. The reaction rate of the phase transfer reaction can be increased by ultrasound, but frequency and power of ultrasound and the geometry of the ultrasonic field inside the reactor influence the reaction strongly. The results demonstrate clearly, that to achieve a high efficiency of ultrasonic systems in chemical processes the ultrasonic parameters and geometry of the sonotrode had to be adopted.

Journal Article↗