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Biomedical subjects

J S Pedersen

Publications and source records attributed to J S Pedersen.

At least 19 recordsLinked to original sources
PubMed2006

Bone nanostructure near titanium and porous tantalum implants studied by scanning small angle x-ray scattering.

Bone sections including either titanium or porous tantalum implant devices used for interbody spinal fusion were investigated with position-resolved small angle X-ray scattering (sSAXS). The samples were obtained from six-month-old pigs that had undergone surgery three months prior to sacrifice. The aim of the study was to explore the possibility of using sSAXS to obtain information about thickness, orientation and shape/arrangement of the mineral crystals in bone near the implant surfaces. Detailed sSAXS scans were carried out in two different regions of bone adjacent to the implant in each of the implant samples. In the implant vicinity the mineral crystals tended to be aligned with the surface of the implants. The mean crystal thickness was between 2.1 and 3.0 nm. The mineral crystal thickness increased linearly with distance from the implant in both regions of the porous tantalum implant and in one of the regions in the titanium sample. In the second region of the titanium sample the thickest mineral crystals were found close to the implant surface. The observed differences in mineral thickness with distance from the implant surfaces might be explained by differences in mechanical load induced by the implant material and the geometrical design of the implant. The study shows that sSAXS is a powerful tool to characterize the nanostructure of bone near implant surfaces.

Humans↗
PubMed2006

The UCSC genome browser database: update 2007.

The University of California, Santa Cruz Genome Browser Database contains, as of September 2006, sequence and annotation data for the genomes of 13 vertebrate and 19 invertebrate species. The Genome Browser displays a wide variety of annotations at all scales from the single nucleotide level up to a full chromosome and includes assembly data, genes and gene predictions, mRNA and EST alignments, and comparative genomics, regulation, expression and variation data. The database is optimized for fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. In the past year, 22 new assemblies and several new sets of human variation annotation have been released. New features include VisiGene, a fully integrated in situ hybridization image browser; phyloGif, for drawing evolutionary tree diagrams; a redesigned Custom Track feature; an expanded SNP annotation track; and many new display options. The Genome Browser, other tools, downloadable data files and links to documentation and other information can be found at http://genome.ucsc.edu/.

Animals↗
PubMed2006

The UCSC Genome Browser Database: update 2006.

The University of California Santa Cruz Genome Browser Database (GBD) contains sequence and annotation data for the genomes of about a dozen vertebrate species and several major model organisms. Genome annotations typically include assembly data, sequence composition, genes and gene predictions, mRNA and expressed sequence tag evidence, comparative genomics, regulation, expression and variation data. The database is optimized to support fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. The Genome Browser displays a wide variety of annotations at all scales from single nucleotide level up to a full chromosome. The Table Browser provides direct access to the database tables and sequence data, enabling complex queries on genome-wide datasets. The Proteome Browser graphically displays protein properties. The Gene Sorter allows filtering and comparison of genes by several metrics including expression data and several gene properties. BLAT and In Silico PCR search for sequences in entire genomes in seconds. These tools are highly integrated and provide many hyperlinks to other databases and websites. The GBD, browsing tools, downloadable data files and links to documentation and other information can be found at http://genome.ucsc.edu/.

Amino Acid Sequence↗
PubMed2005

Loss of Wolbachia infection during colonisation in the invasive Argentine ant Linepithema humile.

WOLBACHIA are maternally inherited bacteria, which are very common in arthropods and nematodes. Wolbachia infection may affect host reproduction through feminisation, parthenogenesis, male-killing, cytoplasmic incompatibility and increased fecundity. Previous studies showing discrepancies between the phylogenies of Wolbachia and its arthropod hosts indicate that infection is frequently lost, but the causes of symbiont extinction have so far remained elusive. Here, we report data showing that colonisation of new habitats is a possible mechanism leading to the loss of infection. The presence and prevalence of Wolbachia were studied in three native and eight introduced populations of the Argentine ant Linepithema humile. The screening shows that the symbiont is common in the three native L. humile populations analysed. In contrast, Wolbachia was detected in only one of the introduced populations. The loss of infection associated with colonisation of new habitats may result from drift (founder effect) or altered selection pressures in the new habitat. Furthermore, a molecular phylogeny based on sequences of the Wolbachia wsp gene indicates that L. humile has been infected by a single strain. Horizontal transmission of the symbiont may be important in ants as suggested by the sequence similarity of strains in the three genera Linepithema, Acromyrmex, and Solenopsis native from South and Central America.

Animals↗
PubMed2002

Convergent development of low-relatedness supercolonies in Myrmica ants.

Many ant species have independently evolved colony structures with multiple queens and very low relatedness among nestmate workers, but it has remained unclear whether low-relatedness kin structures can repeatedly arise in populations of the same species. Here we report a study of Danish island populations of the red ant Myrmica sulcinodis and show that it is likely that such repeated developments occur. Two microsatellite loci were used to estimate genetic differentiation (F(ST)) among three populations and nestmate relatedness within these populations. The F(ST) values were highly significant due to very different allele frequencies among the three populations with relatively few common alleles and relatively many rare alleles, possibly caused by single queen foundation and rare subsequent immigration. Given the isolation of the islands and the low investment in reproduction, we infer that each of the populations was most likely established by a single queen, even though all three extant populations now have within-colony relatedness 95%), and the genetic differentiation of nests showed a significantly positive correlation with the distance between them. Both male-biased sex-ratio and genetic viscosity are expected characteristics of populations where queens have very local dispersal and where new colonies are initiated through nest-budding. Based on a comparison with other M. sulcinodis populations we hypothesise a distinct succession of population types and suggest that this may be a possible pathway to unicoloniality, ie, development towards a complete lack of colony kin structure and unrelated nestmate workers.

Animals↗
PubMed2001

Block copolymer micelle coronas as quasi-two-dimensional dilute or semidilute polymer solutions.

Chain-chain interactions in a corona of polymers tethered to a spherical core under good solvent conditions are studied using Monte Carlo simulations. The total scattering function of the corona as well as different partial contributions are sampled. By combining the different contributions in a self-consistent approach, it is demonstrated that the corona can be regarded as a quasi-two-dimensional polymer solution, with a concentration dependence analogous to that of an ordinary polymer solution. Scattering due to the corona profile and density fluctuation correlations are separated in this approach. The osmotic compressibility is extracted from the latter, and it is shown to be a universal function of surface coverage, with some deviations at high coverage due to surface curvature effects.

Biophysics↗
PubMed2001

Droplet polydispersity and shape fluctuations in AOT [bis(2-ethylhexyl)sulfosuccinate sodium salt] microemulsions studied by contrast variation small-angle neutron scattering.

Microemulsions consisting of AOT water, and decane or iso-octane are studied in the region of the phase diagram where surfactant covered water droplets are formed. The polydispersity and shape fluctuations of the microemulsion droplets are determined and compared in the two different alkane types. Conductivity measurements show that there is a pronounced dependence of the temperature behavior of the microemulsion on the type of alkane used. In both cases the microemulsion droplets start to form larger aggregates when the temperature increases. But in the system with decane this aggregation temperature occurs at a temperature about 10 degrees C lower than in a similar system with iso-octane. Aggregation phenomena are avoided and the two systems are at approximately the same reduced temperature with respect to the aggregation temperature when the temperature of the AOT/D(2)O/decane microemulsion is 10 degrees C and the temperature of the AOT/D(2)O/iso-octane microemulsion is 20 degrees C. Contrast variation small-angle neutron scattering measurements are performed at these temperatures on systems with volume fractions of 5% D2O+AOT by varying the scattering length density of the alkane. The small-angle scattering for 11 different contrasts evenly distributed around the match points are studied for each sample. The scattering data for the different contrasts are analyzed using a molecular constrained model for ellipsoidal droplets of water covered by AOT, interacting as polydisperse hard spheres. All contrasts are fitted simultaneously by taking the different contrast factors into account. The analysis show that at the same reduced temperature with respect to the aggregation temperature the droplet size, polydispersity index, the size of the shape fluctuations are similar in the two systems. A polydispersity index (sigma/R of the Gaussian size distribution) of 16% and an average axis ratio of the droplets of 1.56 is found in the AOT/D(2)O/decane microemulsion. In the AOT/D(2)O/iso-octane system the polydispersity index is also 16% while the axis ratio is 1.72. The bending elastic constant kappa and the Gaussian bending elastic constant kappa; can be estimated from these numbers. For AOT/D(2)O/decane we find kappa=3.4 k(B)T and kappa=-5.9 k(B)T and for AOT/D(2)O/iso-octane we find kappa=2.35k(B)T and kappa=-3.8k(B)T, where k(B) is the Boltzmann constant and T is the absolute temperature.

Journal Article↗
PubMed2001

Phase II clinical trial of preoperative combined chemoradiation for T3 and T4 resectable rectal cancer: preliminary results.

PURPOSE: Although preoperative chemoradiation for high-risk rectal cancer may improve survival and local recurrence rate, its adverse effects are not well defined. This prospective study evaluated the use of preoperative chemoradiation for T3 and T4 resectable rectal cancer, with special emphasis on treatment morbidity, pathologic remission rate, quality of life, and anorectal function. METHODS: Forty-two patients (30 men, 12 women) were enrolled in the study. Median distance of the distal tumor margin from the anal verge was 6.5 cm. Preoperative staging was based on digital rectal examination, endorectal ultrasound, and computed tomography. None of the patients had distant metastases. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (350 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33. Quality of life was assessed with the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire (QLQ-C30) and its colorectal cancer-specific module (QLQ-CR38) questionnaires. Objective anorectal function was assessed by anorectal manometry and pudendal nerve terminal motor latency. Surgery was performed 46 (range, 24-63) days after completion of adjuvant therapy. RESULTS: Nineteen patients (45 percent) had Grade 3 or 4 chemoradiation-induced toxic reactions. Four patients developed intercurrent distant metastases or intraperitoneal carcinomatosis at completion of chemoradiation. Thirty-eight patients underwent surgical resection: abdominoperineal resection, anterior resection, and Hartmann's procedure were performed in 55 percent, 39 percent (11 of 15 patients had a diverting stoma), and 5 percent, respectively. Major surgical complications occurred in 7 patients (18 percent) and included anastomotic leak (n = 1), pelvic abscess (n = 1), small-bowel obstruction (n = 3), and wound breakdown (n = 2). Final pathology was Stage 0 (no residual disease), I, II, and III in 6 (16 percent), 7 (18 percent), 9 (24 percent), and 16 (42 percent) patients, respectively. There was a deterioration, after chemoradiation and surgery, in the quality of life on all subscales assessed, with physical, role, and social function being most severely affected. The symptoms most adversely affected were micturition, defecation, and gastrointestinal problems. Body image and sexual enjoyment deteriorated in both men and women. Chemoradiation alone led to prolonged pudendal nerve terminal motor latency in 57 percent of 7 patients assessed. CONCLUSION: Preliminary results have identified defined costs with preoperative chemoradiation, which included treatment-induced toxicity, a high stoma rate, and adverse effects on quality of life and anorectal function.

Adenocarcinoma↗
PubMed1999

Association behavior of native beta-lactoglobulin.

The association behavior of beta-lactoglobulin has been studied by small-angle neutron scattering as a function of protein concentration, temperature, pH, and NaCl concentration of the solution. By indirect Fourier transformation of the spectra, pair-distance distribution functions for the various samples were obtained. These functions provided information on the maximum size, the weight-averaged molecular mass, and the z-averaged radius of gyration of the beta-lactoglobulin particles. At room temperature and pH values below 4 and above 5.2 the protein consists predominantly of monomers and dimers, consistent with literature. In these pH regimes the formation of dimers is favored upon increasing ionic strength and decreasing protein charge (pH values closer to the isoelectric point of the protein). Around pH 4.7, larger oligomeric structures are formed, enhanced by a decrease in temperature and a decrease in ionic strength. beta-Lactoglobulin A associates more strongly than beta-lactoglobulin B. Surprisingly, at pH 6.9 larger structures than dimers seem to be formed at high protein concentrations (> 30 mg mL-1).

Animals↗
PubMed1998

Ancient conservation of trinucleotide microsatellite loci in polistine wasps.

Microsatellites have proven to be very useful genetic markers for studies of kinship, parentage, and gene mapping. If microsatellites are conserved among species, then those developed for one species can be used on related species, which would save the time and effort of developing new loci. We evaluated conservation of 27 trinucleotide loci that were derived from 2 species of Polistes wasps in cross-species applications on 27 species chosen from the major lineages of the Vespidae, which diverged as much as 144 million years ago. We further investigated cross-species polymorphism levels for 18 of the loci. There was a clear relationship between cladistic distance and both conservation of the priming sites and heterozygosity. However the loci derived from P. bellicosus were much more widely conserved and polymorphic than were those derived from P. annularis. The disparity in cross-species utility between these sets of loci means that caution should be used in generalizing from conservation rates derived from single species. We found no relationship between locus conservation or heterozygosity and GC content of flanks, repeat motif, repeat length, or heterozygosity in the original species, which suggests that generalizations from other studies reporting such patterns are premature.

Animals↗
PubMed1998

Loss of the expression and localization of inhibin alpha-subunit in high grade prostate cancer.

Serum inhibin levels are elevated in postmenopausal women with granulosa and mucinous epithelial tumors of the ovary. In contrast, functional deletion of the inhibin alpha gene in male and female mice results in the development of primary gonadal granulosa/Sertoli cell tumors. The aim of this study was to determine whether inhibin alpha-subunit gene and protein expression are altered in prostate cancer. Messenger ribonucleic acid expression was studied by in situ hybridization, and protein localization was studied by immunohistochemistry. Inhibin alpha-subunit messenger ribonucleic acid expression and protein localization were observed in the epithelium of tissues from men with benign prostatic hyperplasia, in regions of basal cell hyperplasia, and in nonmalignant regions of tissue from men with high grade prostate cancer. In the malignant regions of tissue from men with high grade prostate cancer, the expression of the inhibin alpha-subunit gene was suppressed and was not detectable in poorly differentiated tumor cells. These results demonstrate that in contrast to ovarian granulosa cell tumors, inhibin alpha gene expression is down-regulated in poorly differentiated prostate cancer.

Carcinoma↗
PubMed1997

Solution scattering structural analysis of the 70 S Escherichia coli ribosome by contrast variation. I. Invariants and validation of electron microscopy models.

Solutions of selectively deuterated 70 S Escherichia coli ribosomes and of free 30 S and 50 S subunits were studied by neutron scattering using contrast variation. The integrity of the partially deuterated particles was controlled by parallel X-ray measurements. Integral parameters of the entire ribosome, of its subunits and of the protein and rRNA moieties were evaluated. The data allow an experimental validation of the two most recent electron microscopy reconstructions of the 70 S ribosome presented by the groups of J. Frank (Albany) and of M. van Heel & R. Brimacombe (Berlin). For each reconstruction, integral parameters and theoretical scattering curves from the 70 S and its subunits were calculated and compared with the experimental data. Although neither of the two models yields a comprehensive agreement with the experimental data, Frank's model provides a better fit. For the 50 S subunit of van Heel & Brimacombe's model the fit with the experimental data improves significantly when the internal channels and tunnels are filled up. The poorer fit of the latter model is thus caused by its "sponge"-like structure which may partly be due to an enhancement of high frequency contributions in some of the steps of the three-dimensional image reconstruction. It seems therefore unlikely that the ribosome has a "sponge"-like structure with a pronounced network of channels.

Deuterium↗
PubMed1997

Solution scattering structural analysis of the 70 S Escherichia coli ribosome by contrast variation. II. A model of the ribosome and its RNA at 3.5 nm resolution.

Selectively deuterated 70 S E. coli ribosomes and isolated 30 S and 50 S subunits were analyzed by X-ray and neutron solution scattering. The resulting contrast variation data set (42 curves in total) was proven to be consistent in describing the ribosome as a four-phase system composed of the protein and rRNA moieties of both subunits. This data set thus provides ten times more information than a single scattering curve. A solid body four-phase model of the 70 S ribosome at low resolution was built from the envelope functions of the 30 S and 50 S subunits and of those of the corresponding RNA moieties. The four envelopes were parameterized at a resolution of 3.5 nm using spherical harmonics and taking into account interface layers between the phases. The initial approximation for the envelopes of the subunits was taken from electron microscopic data presented recently by J. Frank and co-workers (Albany); the rRNA envelopes were initially approximated by spheres. The optimization and the refinement of the model proceeded by non-linear least squares minimization fitting the available experimental data. The refined envelopes of the subunits differ by about 10% from the starting approximation and the shape of the final 70 S model lies between the outer envelopes of the models by Frank and by M. von Heel & R. Brimacombe (Berlin). The rRNA moiety in the 30 S subunit is more anisometric than the subunit itself, whereas the rRNA of the 50 S subunit forms a compact core. The rRNAs protrude to the surfaces of the subunits and occupy approximately 30 to 40% of the corresponding surface areas. X-ray scattering curves of the two main functional elongation 70 S complexes (pre- and post-translocational) differ only marginally from those of the non-programmed ribosomes, suggesting that the low resolution four-phase model is also valid for the elongating 70 S ribosome.

Escherichia coli↗
PubMed1996

Structural model of the 50S subunit of E. coli ribosomes from solution scattering.

The application of new methods of small-angle scattering data interpretation to a contrast variation study of the 50S ribosomal subunit of Escherichia coli in solution is described. The X-ray data from contrast variation with sucrose are analyzed in terms of the basic scattering curves from the volume inaccessible to sucrose and from the regions inside this volume occupied mainly by RNA and by proteins. From these curves models of the shape of the 50S and its RNA-rich core are evaluated and positioned so that their difference produces a scattering curve which is in good agreement with the scattering from the protein moiety. Based on this preliminary model, the X-ray and neutron contrast variation data of the 50S subunit in aqueous solutions are interpreted in the frame of the advanced two-phase model described by the shapes of the 50S subunit and its RNA-rich core taking into account density fluctuations inside the RNA and the protein moiety. The shape of the envelope of the 50S subunit and of the RNA-rich core are evaluated with a resolution of about 40 A. The shape of the envelope is in good agreement with the models of the 50S subunit obtained from electron microscopy on isolated particles. The shape of the RNA-rich core correlates well with the model of the entire particle determined by the image reconstruction from ordered sheets indicating that the latter model which is based on the subjective contouring of density maps is heavily biased towards the RNA.

Escherichia coli↗
PubMed1994

Solution scattering from 50S ribosomal subunit resolves inconsistency between electron microscopic models.

Models of the 50S ribosomal subunit from electron microscopy on isolated particles and on ordered sheets display significantly different features. A model of the shape of the native Escherichia coli 50S subunit in solution and of its RNA-rich core at 4-nm resolution has been produced by using methods for joint interpretation of x-ray and neutron small-angle scattering data obtained by contrast variation. The good agreement between the shape of the entire 50S subunit and the electron microscopic models of isolated particles and between the RNA-rich core and the model obtained from ordered sheets leads to the conclusion that the latter, which is based on the subjective contouring of density maps, is heavily biased toward the RNA.

Escherichia coli↗
PubMed1994

Structural model of the 50 S subunit of Escherichia coli ribosomes from solution scattering. II. Neutron scattering study.

The X-ray and neutron contrast variation data of the 50 S ribosomal subunit of Escherichia coli in solution are interpreted in the frame of a two-phase model described by the shapes of the 50 S subunit and its RNA-rich core taking into account density fluctuations inside the RNA and the protein moiety. The shape of the envelope of the 50 S subunit and of the RNA-rich core are evaluated with a resolution of about 4 nm. The shape of the envelope is in good agreement with the models of the 50 S subunit obtained from electron microscopy on isolated particles. The shape of the RNA-rich core correlates well with the model of the entire particle determined by the image reconstruction from ordered sheets indicating that the latter model which is based on the subjective contouring of density maps is heavily biased towards the RNA.

Escherichia coli↗