Biomedical subjects

Anders Berglund

Publications and source records attributed to Anders Berglund.

11 recordsLinked to original sources

PubMed2005

Sequence signature analysis of chromosome identity in three Drosophila species.

BACKGROUND: All eukaryotic organisms need to distinguish each of their chromosomes. A few protein complexes have been described that recognise entire, specific chromosomes, for instance dosage compensation complexes and the recently discovered autosome-specific Painting of Fourth (POF) protein in Drosophila. However, no sequences have been found that are chromosome-specific and distributed over the entire length of the respective chromosome. Here, we present a new, unbiased, exhaustive computational method that was used to probe three Drosophila genomes for chromosome-specific sequences. RESULTS: By combining genome annotations and cytological data with multivariate statistics related to three Drosophila genomes we found sequence signatures that distinguish Muller's F-elements (chromosome 4 in D. melanogaster) from all other chromosomes in Drosophila that are not attributable to differences in nucleotide composition, simple sequence repeats or repeated elements. Based on these signatures we identified complex motifs that are strongly overrepresented in the F-elements and found indications that the D. melanogaster motif may be involved in POF-binding to the F-element. In addition, the X-chromosomes of D. melanogaster and D. yakuba can be distinguished from the other chromosomes, albeit to a lesser extent. Surprisingly, the conservation of the F-element sequence signatures extends not only between species separated by approximately 55 Myr, but also linearly along the sequenced part of the F-elements. CONCLUSION: Our results suggest that chromosome-distinguishing features are not exclusive to the sex chromosomes, but are also present on at least one autosome (the F-element) in Drosophila.

Animals↗

PubMed2005

The equilibrium unfolding of MerP characterized by multivariate analysis of 2D NMR data.

A general problem when analysing NMR spectra that reflect variations in the environment of target molecules is that different resonances are affected to various extents. Often a few resonances that display the largest frequency changes are selected as probes to reflect the examined variation, especially in the case, where the NMR spectra contain numerous resonances. Such a selection is dependent on more or less intuitive judgements and relying on the observed spectral variation being primarily caused by changes in the NMR sample. Second, recording changes observed for a few (albeit significant) resonances is inevitably accompanied by not using all available information in the analysis. Likewise, the commonly used chemical shift mapping (CSM) [Biochemistry 39 (2000) 26, Biochemistry 39 (2000) 12595] constitutes a loss of information since the total variation in the data is not retained in the projection into this single variable. Here, we describe a method for subjecting 2D NMR time-domain data to multivariate analysis and illustrate it with an analysis of multiple NMR experiments recorded at various folding conditions for the protein MerP. The calculated principal components provide an unbiased model of variations in the NMR spectra and they can consequently be processed as NMR data, and all the changes as reflected in the principal components are thereby made available for visual inspection in one single NMR spectrum. This approach is much less laborious than consideration of large numbers of individual spectra, and it greatly increases the interpretative power of the analysis.

Fourier Analysis↗

PubMed2005

Genetic structure in the coral-reef-associated Banggai cardinalfish, Pterapogon kauderni.

In this study, we used 11 polymorphic microsatellite loci to show that oceanic distances as small as 2-5 km are sufficient to produce high levels of population genetic structure (multilocus F(ST) as high as 0.22) in the Banggai cardinalfish (Pterapogon kauderni), a heavily exploited reef fish lacking a pelagic larval dispersal phase. Global F(ST) among all populations, separated by a maximum distance of 203 km, was 0.18 (R(ST) = 0.35). Moreover, two lines of evidence suggest that estimates of F(ST) may actually underestimate the true level of genetic structure. First, within-locus F(ST) values were consistently close to the theoretical maximum set by the average within-population heterozygosity. Second, the allele size permutation test showed that R(ST) values were significantly larger than F(ST) values, indicating that populations have been isolated long enough for mutation to have played a role in generating allelic variation among populations. The high level of microspatial structure observed in this marine fish indicates that life history traits such as lack of pelagic larval phase and a good homing ability do indeed play a role in shaping population genetic structure in the marine realm.

Animals↗

PubMed2004

A high-resolution transcript profile across the wood-forming meristem of poplar identifies potential regulators of cambial stem cell identity.

Plant growth is the result of cell proliferation in meristems, which requires a careful balance between the formation of new tissue and the maintenance of a set of undifferentiated stem cells. Recent studies have provided important information on several genetic networks responsible for stem cell maintenance and regulation of cell differentiation in the apical meristems of shoots and roots. Nothing, however, is known about the regulatory networks in secondary meristems like the vascular cambium of trees. We have made use of the large size and highly regular layered organization of the cambial meristem to create a high-resolution transcriptional map covering 220 microm of the cambial region of aspen (Populus tremula). Clusters of differentially expressed genes revealed substantial differences in the transcriptomes of the six anatomically homogenous cell layers in the meristem zone. Based on transcriptional and anatomical data, we present a model for the position of the stem cells and the proliferating mother cells in the cambial zone. We also provide sets of marker genes for different stages of xylem and phloem differentiation and identify potential regulators of cambial meristem activity. Interestingly, analysis of known regulators of apical meristem development indicates substantial similarity in regulatory networks between primary and secondary meristems.

Cell Differentiation↗

PubMed2004

ProVal: a protein-scoring function for the selection of native and near-native folds.

A low-resolution scoring function for the selection of native and near-native structures from a set of predicted structures for a given protein sequence has been developed. The scoring function, ProVal (Protein Validate), used several variables that describe an aspect of protein structure for which the proximity to the native structure can be assessed quantitatively. Among the parameters included are a packing estimate, surface areas, and the contact order. A partial least squares for latent variables (PLS) model was built for each candidate set of the 28 decoy sets of structures generated for 22 different proteins using the described parameters as independent variables. The C(alpha) RMS of the candidate structures versus the experimental structure was used as the dependent variable. The final generalized scoring function was an average of all models derived, ensuring that the function was not optimized for specific fold classes or method of structure generation of the candidate folds. The results show that the crystal structure was scored best in 64% of the 28 test sets and was clearly separated from the decoys in many examples. In all the other cases in which the crystal structure did not rank first, it ranked within the top 10%. Thus, although ProVal could not distinguish between predicted structures that were similar overall in fold quality due to its inherently low resolution, it can clearly be used as a primary filter to eliminate approximately 90% of fold candidates generated by current prediction methods from all-atom modeling and further evaluation. The correlation between the predicted and actual C(alpha) RMS values varies considerably between the candidate fold sets.

Computational Biology↗

PubMed2004

An overview of the current status of national reporting systems for adverse reactions to dental materials.

OBJECTIVES: Since all dental materials pose a potential risk to patients and members of the dental team, the post-market monitoring of adverse reactions caused by dental materials should be considered essential. This article reviews the current status of post-market monitoring of adverse reactions to dental materials and highlights some of the issues that arise in trying to establish an evidence base on the characteristics of adverse reactions to dental materials. METHODS: Norway, Sweden and more recently the UK have sought to monitor adverse reactions to dental materials systematically and proactively in an effort to add to the evidence base on the safety of dental materials. Their experiences in undertaking post-market surveillance have been combined in preparing this article. RESULTS: To date the Norwegian, Swedish and the UK projects has received 1268 reports over 11 years, 848 reports over 5.5 years and 1117 reports over 3 years, respectively, relating to adverse reactions seen or experienced by dental personnel and patients. Presently, there are no harmonized criteria for what can be classified as an adverse reaction related to dental materials. Under reporting is a recognised problem and lack of awareness and lack of clarity as to what constitutes an adverse reaction may be contributory factors. A pro-active reporting system takes a considerable time to become established, but can generate a lot of potentially useful information. CONCLUSIONS: There is a need to raise the awareness among dental professionals of the potential for adverse reactions due to dental materials and to develop an internationally accepted system of data gathering that can produce the evidence that reflect the extent, severity and incidence of adverse reactions to dental materials.

Adult↗

PubMed2003

What affects mRNA levels in leaves of field-grown aspen? A study of developmental and environmental influences.

We have analyzed the abundance of mRNAs expressed from 11 nuclear genes in leaves of a free-growing aspen (Populus tremula) tree throughout the growing season. We used multivariate statistics to determine the influence of environmental factors (i.e. the weather before sampling) and developmental responses to seasonal changes at the mRNA level for each of these genes. The gene encoding a germin-like protein was only expressed early in the season, whereas the other tested genes were expressed throughout the season and showed mRNA variations on a day-to-day basis. For six of the genes, reliable models were found that described the mRNA level as a function of weather, but the leaf age was also important for all genes except one encoding an early light-inducible protein (which appeared to be regulated purely by environmental factors under these conditions). The results confirmed the importance of several environmental factors previously shown to regulate the genes, but we also detected a number of less obvious factors (such as the variation in weather parameters and the weather of the previous day) that correlated with the mRNA levels of individual genes. The study shows the power of multivariate statistical methods in analyzing gene regulation under field conditions.

Gene Expression Regulation, Developmental↗

PubMed2003

A multivariate approach applied to microarray data for identification of genes with cell cycle-coupled transcription.

We have analyzed microarray data using a modeling approach based on the multivariate statistical method partial least squares (PLS) regression to identify genes with periodic fluctuations in expression levels coupled to the cell cycle in the budding yeast, Saccharomyces cerevisiae. PLS has major advantages for analyzing microarray data since it can model data sets with large numbers of variables and with few observations. A response model was derived describing the expression profile over time expected for periodically transcribed genes, and was used to identify budding yeast transcripts with similar profiles. PLS was then used to interpret the importance of the variables (genes) for the model, yielding a ranking list of how well the genes fitted the generated model. Application of an appropriate cutoff value, calculated from randomized data, allows the identification of genes whose expression appears to be synchronized with cell cycling. Our approach also provides information about the stage in the cell cycle where their transcription peaks. Three synchronized yeast cell microarray data sets were analyzed, both separately and combined. Cell cycle-coupled periodicity was suggested for 455 of the 6,178 transcripts monitored in the combined data set, at a significance level of 0.5%. Among the candidates, 85% of the known periodic transcripts were included. Analysis of the three data sets separately yielded similar ranking lists, showing that the method is robust.

Algorithms↗

PubMed2003

Impact of azaproline on amide cis-trans isomerism: conformational analyses and NMR studies of model peptides including TRH analogues.

The beta-turn is a well-studied motif in both proteins and peptides. Four residues, making almost a complete 180 degree-turn in the direction of the peptide chain, define the beta-turn. Several types of the beta-turn are defined according to Phi and Psi torsional angles of the backbone for residues i + 1 and i + 2. One special type of beta-turn, the type VI-turn, usually contains a proline with a cis-amide bond at residue i + 2. In an aza-amino acid, the alpha-carbon of the amino acid is changed to nitrogen. Peptides containing azaproline (azPro) have been shown to prefer the type VI beta-turn both in crystals and in organic solvents by NMR studies. MC/MD simulations using the GB/SA solvation model for water explored the conformational preferences of azPro-containing peptides in aqueous systems. An increase in the conformational preference for the cis-amide conformer of azPro was clearly seen, but the increased stability was relatively minor with respect to the trans-conformer as compared to previous suggestions. To test the validity of the calculations in view of the experimental data from crystal structures and NMR in organic solvents, [azPro(3)]-TRH and [Phe(2), azPro(3)]-TRH were synthesized, and their conformational preferences were determined by NMR in polar solvents as well as the impact of the azPro substitution on their biological activities.

Aza Compounds↗

PubMed2003

Surface analysis of dental amalgams by X-ray photoelectron spectroscopy and X-ray diffraction.

OBJECTIVES: It is important to characterize the surface of dental amalgam in order to understand the process of mercury release from amalgam restorations in the oral cavity. The mercury evaporation occurs not only from the newly made restoration but also from the set material. METHODS: The surfaces of four different types of amalgams, which had been well set, were analyzed with X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) and the relationship between surface compositions and mercury release was studied. Fresh amalgam surfaces as well as aged surfaces, which were stored for 30 days in air, were investigated using XPS and the chemical states of amalgam components and oxygen were studied. The aged surfaces were also characterized with XRD and grazing angle XRD. RESULTS: With increased oxidation, the surface contents of tin and oxygen were increased in all amalgams. In contrast, the surface contents of copper and mercury were decreased. An increase of zinc or indium content were observed in zinc or indium containing amalgams, respectively. A surface layer enriched with indium and oxygen was clearly detected by XPS but not with grazing angle XRD. SIGNIFICANCE: The thickness of the enriched surface layer is estimated to be in the order of few nanometer, which is approximately equal to the analysis depth of XPS. In addition, the presence of metallic elements, like tin and zinc, that readily form a stable oxide layer at the surface suppress the release of mercury.

Copper↗

PubMedDate not supplied

Hierarchical PLS modeling for predicting the binding of a comprehensive set of structurally diverse protein-ligand complexes.

A new approach is presented for predicting ligand binding to proteins using hierarchical partial-least-squares regression to latent structures (Hi-PLS). Models were based on information from the 2002 release of the PDBbind database containing (after in-house refinement) high-resolution X-ray crystallography and binding affinity (Kd or Ki) data for 612 protein-ligand complexes. The complexes were characterized by four different descriptor blocks: three-dimensional (3D) structural descriptors of the proteins, protein-ligand interactions according to the Validate scoring function, binding site surface areas, and ligand 2D and 3D descriptors. These descriptor blocks were used in Hi-PLS models, generated using both linear and nonlinear terms, to relate the characterizations to pKd/i. The results show that each of the four descriptor blocks contributed to the model, and the predictions of pKd/i of the internal test set gave a root-mean-square error of prediction (RMSEP) of 1.65. The data were further divided according to the structural classification of the proteins, and Hi-PLS models were constructed for the resulting subclasses. The models for the four subclasses differed considerably in terms of both their ability to predict pKd/i (with RMSEPs ranging from 0.8 to 1.56) and the descriptor block that had the strongest influence. The models were validated with an external test set of 174 complexes from the 2003 release of the PDBbind database. The overall results show that the presented Hi-PLS methodology could facilitate the difficult task of predicting binding affinity.

Crystallography, X-Ray↗