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Biomedical subjects

D Suter

Publications and source records attributed to D Suter.

At least 19 recordsLinked to original sources

Biomass allocation is an important determinant of the tannin concentration in growing plants.

BACKGROUND AND AIMS: Condensed tannins (CTs) in the diet affect consumers in a concentration-dependent manner. Because of their importance in plant defence against herbivores and pathogens as well as their potential application against gastrointestinal parasites of ruminants in agronomy, an understanding of the seasonal dynamics of CT concentrations during plant growth is essential. METHODS: Over a vegetation period, CT concentrations in leaves, stems and roots and the biomass proportions between these organs were investigated in Onobrychis viciifolia, Lotus corniculatus and Cichorium intybus. Based on the experimental data, a model has been suggested to predict CT concentrations in harvestable biomass of these species. KEY RESULTS: During the experiment, leaf mass fractions of plants decreased from 85, 64, 85 to 30, 18, 39 % d. wt in Onobrychis, Lotus and Cichorium, respectively, and proportions of stems and roots increased accordingly. While CT concentrations almost doubled in leaves in Onobrychis (from 52 to 86 mg g(-1) d. wt, P<0.001) and Lotus (from 25 to 54 mg g(-1) d. wt, P<0.001), they were stable at low levels in expanding leaves of Cichorium (5 mg g(-1) d. wt) and in stems and roots of all investigated species. Due to an inverse effect of the increasing CT concentrations in leaves and simultaneous dilution from increasing proportions of 'CT-poor' stems, CT concentrations in harvestable biomass were stable over time in all investigated species: 62, 26 and 5 mg g(-1) d. wt for Onobrychis, Lotus and Cichorium, respectively. CONCLUSIONS: As a consequence of the unequal distribution of tannins in different plant parts and due to the changing biomass proportions between them, various herbivores (e.g. a leaf-eating insect and a grazing ruminant) may find not only different concentrations of CT in their diets but also different CT dynamics during the season. For the prediction of seasonal variations of CT concentrations, biomass allocation and accumulation of none-CT plant material are likely to be as important predictors as the knowledge of CT synthesis and its regulation.

Biomass↗

Antimicrobial resistance of Yersinia enterocolitica strains from human patients, pigs and retail pork in Switzerland.

To obtain basic data for future resistance monitoring programs, 386 Yersinia enterocolitica strains from human patients, raw retail pork and pig feces were tested for their susceptibilities to 16 antimicrobial agents and two antimicrobial growth promoters (carbadox and olaquindox). No strains were resistant to ceftriaxone, cefuroxime, ciprofloxacine, gentamicin, kanamycin, neomycin or polymyxin. Although in Switzerland carbadox and olaquindox were used as growth promoters for pigs for over 25 years, all strains were susceptible to them. In contrast, there were high levels of resistance to ampicillin, cefalothin and amoxicillin/clavulanic acid. Less than 10% of clinical isolates and strains from pig feces were resistant to streptomycin, sulfonamide, trimethoprim/sulfamethoxazole, tetracyclin, trimethoprim and chloramphenicol, but strains from retail pork were all susceptible to these antimicrobial agents. This finding suggested that pork is probably not a major source of Y. enterocolitica that cause human infections in Switzerland. A difference between clinical isolates and strains from pork was also shown by serotyping. Clinical isolates frequently belonged to the O3 and O9 groups whereas these two serotypes were not found in strains from pork. Resistance to multiple antimicrobial agents was rare. When examined by pulsed field gel electrophoresis (PFGE), two strains of fecal origin with an identical pattern of resistance to six antimicrobial agents were shown to be unrelated. Of four clinical isolates with resistances to five antimicrobial agents, two were of the same pulsotype. Retrospectively, it was found that these strains came from two members of the same household and thus represented a mini-outbreak.

Animals↗

Planar microresonators for EPR experiments.

EPR resonators on the basis of standing-wave cavities are optimised for large samples. For small samples it is possible to design different resonators that have much better power handling properties and higher sensitivity. Other parameters being equal, the sensitivity of the resonator can be increased by minimising its size and thus increasing the filling factor. Like in NMR, it is possible to use lumped elements; coils can confine the microwave field to volumes that are much smaller than the wavelength. We discuss the design and evaluation of EPR resonators on the basis of planar microcoils. Our test resonators, which operate at a frequency of 14 GHz, have excellent microwave efficiency factors, achieving 24 ns pi/2 EPR pulses with an input power of 17 mW. The sensitivity tests with DPPH samples resulted in the sensitivity value 2.3 x 10(9) spins.G(-1) Hz(-1/2) at 300 K.

Journal Article↗

Hypoxia aggravates lipopolysaccharide-induced lung injury.

The animal model of inflammatory response induced by intratracheal application of lipopolysaccharide includes many typical features of acute lung injury or the acute respiratory distress syndrome. A number of experimental investigations have been performed to characterize the nature of this injury more effectively. In inflammatory conditions, hypoxia occurs frequently before and in parallel with pulmonary and non-pulmonary pathological events. This current study was designed to examine the in vivo effect of hypoxia as a potentially aggravating condition in endotoxin-induced lung injury. Lipopolysaccharide, 150 microg, was instilled intratracheally into rat lungs, and thereafter animals were exposed to either normoxia or hypoxia (10% oxygen). Lungs were collected 2, 4, 6 and 8 h later. Inflammatory response and tissue damage were evaluated by quantitative analysis of inflammatory cells and mediators, surfactant protein and vascular permeability. A significantly enhanced neutrophil recruitment was seen in lipopolysaccharide-animals exposed to hypoxia compared to lipopolysaccharide-animals under normoxia. This increased neutrophil accumulation was triggered by inflammatory mediators such as tumour necrosis factor-alpha and macrophage inflammatory protein-1beta, secreted by alveolar macrophages. Determination of vascular permeability and surfactant protein-B showed enhanced concentrations in lipopolysaccharide-lungs exposed to hypoxia, which was absent in animals previously alveolar macrophage-depleted. This study demonstrates that hypoxia aggravates lipopolysaccharide injury and therefore represents a second hit injury. The additional hypoxia-induced inflammatory reaction seems to be predominantly localized in the respiratory compartment, underlining the compartmentalized nature of the inflammatory response.

Animals↗

Wave-vector-dependent exciton exchange interaction.

The exchange interaction for the yellow 1S orthoexciton in Cu2O is derived up to the order K2. The resulting exchange splittings are verified experimentally using high resolution spectroscopy. In agreement with theory the fine structure shows a characteristic dependence on the direction of the wave vector.

Journal Article↗

U7 snRNAs induce correction of mutated dystrophin pre-mRNA by exon skipping.

Most cases of Duchenne muscular dystrophy are caused by dystrophin gene mutations that disrupt the mRNA reading frame. Artificial exclusion (skipping) of a single exon would often restore the reading frame, giving rise to a shorter, but still functional dystrophin protein. Here, we analyzed the ability of antisense U7 small nuclear (sn)RNA derivatives to alter dystrophin pre-mRNA splicing. As a proof of principle, we first targeted the splice sites flanking exon 23 of dystrophin pre-mRNA in the wild-type muscle cell line C2C12 and showed precise exon 23 skipping. The same strategy was then successfully adapted to dystrophic immortalized mdx muscle cells where exon-23-skipped dystrophin mRNA rescued dystrophin protein synthesis. Moreover, we observed a stimulation of antisense U7 snRNA expression by the murine muscle creatine kinase enhancer. These results demonstrate that alteration of dystrophin pre-mRNA splicing could correct dystrophin gene mutations by expression of specific U7 snRNA constructs.

Animals↗

Deconvolution and assignment of different optical transitions of the blue copper protein azurin from optically detected electron paramagnetic resonance spectroscopy.

Magnetic circular dichroism is a powerful spectroscopic tool for the assignment of optical resonance lines. An extension of this technique, microwave-modulated circular dichroism, provides additional details, in particular information about the orientation of optical transition moments. It arises from magnetization precessing around the static magnetic field, excited by a microwave field, in close analogy to electron paramagnetic resonance (EPR). In this paper we investigate the visible and near-infrared spectrum of the blue copper protein Pseudomonas aeruginosa azurin. Using a nonoriented sample (frozen solution), we apply this technique to measure the variation of the optical anisotropy with the wavelength. A comparison with the optical anisotropies of the possible ligand-field and charge-transfer transitions allows us to identify individual resonance lines in the strongly overlapping spectrum and assign them to specific electronic transitions. The technique is readily applicable to other proteins with transition metal centers.

Anisotropy↗

Functional magnetic resonance imaging in real time (FIRE): sliding-window correlation analysis and reference-vector optimization.

New algorithms for correlation analysis are presented that allow the mapping of brain activity from functional MRI (fMRI) data in real time during the ongoing scan. They combine the computation of the correlation coefficients between measured fMRI time-series data and a reference vector with "detrending", a technique for the suppression of non-stimulus-related signal components, and the "sliding-window technique". Using this technique, which limits the correlation computation to the last N measurement time points, the sensitivity to changes in brain activity is maintained throughout the whole experiment. For increased sensitivity in activation detection a fast and robust optimization of the reference vector is proposed, which takes into account a realistic model of the hemodynamic response function to adapt the parameterized reference vector to the measured data. Based on the described correlation method, real-time fMRI experiments using visual stimulation paradigms have been performed successfully on a clinical MR scanner, which was linked to an external workstation for image analysis.

Adult↗

Probing the electronic structure of transition metal ion centres in proteins by coherent Raman-detected electron paramagnetic resonance spectroscopy.

The simultaneous excitation of a paramagnetic sample with optical (laser) and microwave radiation can cause an amplitude or phase modulation of the transmitted light at the microwave frequency. The detection of this modulation indicates the presence of coupled optical and electron paramagnetic resonance (EPR) transitions in the sample. Here we report the first application of this technique to a biomolecule: the blue copper centre of Pseudomonas aeruginosa azurin. Using optical excitation at 686 nm, in the thiol to copper(II) charge transfer band, we measure a coherent Raman-detected EPR spectrum of a frozen aqueous solution. Its lineshape is characteristic of the magnetic circular dichroism along each principal g-value axis. This information allows electronic and structural models of transition metal ion centres in proteins to be tested.

Electron Spin Resonance Spectroscopy↗

Left ventricular motion reconstruction based on elastic vector splines.

In medical imaging it is common to reconstruct dense motion estimates, from sparse measurements of that motion, using some form of elastic spline (thin-plate spline, snakes and other deformable models, etc.). Usually the elastic spline uses only bending energy (second-order smoothness constraint) or stretching energy (first-order smoothness constraint), or a combination of the two. These elastic splines belong to a family of elastic vector splines called the Laplacian splines. This spline family is derived from an energy minimization functional, which is composed of multiple-order smoothness constraints. These splines can be explicitly tuned to vary the smoothness of the solution according to the deformation in the modeled material/tissue. In this context, it is natural to question which members of the family will reconstruct the motion more accurately. We compare different members of this spline family to assess how well these splines reconstruct human cardiac motion. We find that the commonly used splines (containing first-order and/or second-order smoothness terms only) are not the most accurate for modeling human cardiac motion.

Computer Simulation↗

Double-target antisense U7 snRNAs promote efficient skipping of an aberrant exon in three human beta-thalassemic mutations.

We have used three beta-thalassemic mutations, IVS2-654, -705 and -745, that create aberrant 5' splice sites (5' ss) and activate a common cryptic 3' ss further upstream in intron 2 of the human beta-globin gene to optimize a generally applicable exon-skipping strategy using antisense derivatives of U7 small nuclear RNA (snRNA). Introducing a modified U7 snRNA gene carrying an antisense sequence against the cryptic 3' ss into cultured cells expressing the mutant beta-globin genes, restored correct beta-globin mRNA splicing for all three mutations, but the efficiency was much weaker for IVS2-654 than for the other mutations. The length of antisense sequence influenced the efficiency with an optimum of approximately 24 nucleotides. Combining two antisense sequences directed against different target sites in intron 2, either on separate antisense RNAs or, even better, on a single U7 snRNA, significantly enhanced the efficiency of splicing correction. One double-target U7 RNA was expressed on stable transformation resulting in permanent and efficient suppression of the IVS2-654 mutation and production of beta-globin. These results suggest that forcing the aberrant exon into a looped secondary structure may strongly promote its exclusion from the mRNA and that this approach may be used generally to induce exon skipping.

Exons↗

Stable alteration of pre-mRNA splicing patterns by modified U7 small nuclear RNAs.

In several forms of beta-thalassemia, mutations in the second intron of the beta-globin gene create aberrant 5' splice sites and activate a common cryptic 3' splice site upstream. As a result, the thalassemic beta-globin pre-mRNAs are spliced almost exclusively via the aberrant splice sites leading to a deficiency of correctly spliced beta-globin mRNA and, consequently, beta-globin. We have designed a series of vectors that express modified U7 snRNAs containing sequences antisense to either the aberrant 5' or 3' splice sites in the IVS2-705 thalassemic pre-mRNA. Transient expression of modified U7 snRNAs in a HeLa cell line stably expressing the IVS2-705 beta-globin gene restored up to 65% of correct splicing in a sequence-specific and dose-dependent manner. Cell lines that stably coexpressed IVS2-705 pre-mRNA and appropriately modified U7 snRNA exhibited up to 55% of permanent restoration of correct splicing and expression of full-length beta-globin protein. This novel approach provides a potential alternative to gene replacement therapies.

Base Sequence↗

Fanconi-Bickel syndrome--the original patient and his natural history, historical steps leading to the primary defect, and a review of the literature.

UNLABELLED: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism recently demonstrated to be caused by mutations in Glut2, the gene for the glucose transporter protein 2 expressed in liver, pancreas, intestine and kidney. The disease was first described in a 3-year-old Swiss boy in 1949. Here we report a follow up of this original patient over more than 50 years and show that the typical clinical and laboratory findings of FBS (hepatomegaly secondary to glycogen accumulation, glucose and galactose intolerance, fasting hypoglycaemia, a characteristic proximal tubular nephropathy and severe short stature) persist into adulthood. We further summarize the historical observations that eventually led to the identification of the basic defect of FBS and give an overview of the 82 cases from 70 families in the published literature and from personal communications. CONCLUSION: Although with the first description of a congenital defect of facilitative glucose transport the main steps in the pathophysiology of Fanconi-Bickel syndrome have been elucidated, numerous pathophysiological mechanisms are far from clear and thus encourage the ongoing study of patients with this disorder.

Child, Preschool↗

Histone H4 mRNA from the nematode Ascaris lumbricoides is cis-spliced and polyadenylated.

A histone H4 gene from Ascaris lumbricoides contains an intron of approx. 2040 bp. Transcripts of the gene are spliced and polyadenylated. This is the first intron-containing H4 gene described for a metazoan. Notably, H4 mRNA from another nematode, Caenorhabditis elegans, is intron-less and lacks poly A (Roberts, S.B., Emmons, S.W. and Childs, G. (1989) J. Mol. Biol. 206, 567-577).

Animals↗

DT diaphorase exists as a dimer-tetramer equilibrium in solution.

The quaternary behaviour of DT diaphorase in solution has been investigated by hydrodynamics under a range of conditions. At neutral pH DT diaphorase is shown to exist as a tightly-associated homodimer in a dimer-tetramer equilibrium. Concentrations of the chaotropic agent potassium thiocyanate (KSCN) of greater than 200 mM result in irreversible loss of the FAD cofactor and denaturation of the homodimer though this agent appears to be ineffective in disrupting intermolecular association. These data conform to a model in which under extreme dissociation conditions, the folded dimer is in equilibrium with the unfolded monomer and are consistent with evidence from the X-ray structure and proposed catalytic mechanism where both monomers are catalytically interdependent.

Animals↗

[A nursing intervention study in interdisciplinary cooperation: challenges and problem solving strategies].

Doing a nursing intervention study in two hospitals in collaboration with physicians challenged all participating parties. The course of the study was influenced and partially changed by unforeseen problems. This article presents organizational perspectives on carrying through an intervention study while daily patient care is taking place and discusses specific issues of collaborating with physicians and nurses. Problem solving strategies and consequences from experiences with this study are presented.

Cooperative Behavior↗