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Biomedical subjects

A Andreeva

Publications and source records attributed to A Andreeva.

9 recordsLinked to original sources
PubMed2006

Spastin gene mutations in Bulgarian patients with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is an extremely heterogeneous group of neurodegenerative disorders affecting the longest axons in the central nervous system. The most common genetic form accounting for about 40% of the autosomal-dominant HSP (ADHSP) cases is spastin gene, SPG4. We performed mutation screening of the spastin gene on 36 unrelated HSP patients from three different ethnic groups (Bulgarian, Turks and Gypsies) and found four new mutations and one already reported. The phenotype-genotype correlations in Bulgarian SPG4 patients showed a great difference in the age at disease onset between patients with missense mutations and those harboring deletions and splice-site mutations. Our study is the first to present corroborative clinical data in favor of the general hypothesis that the clinical course of the disease is related to the type of the spastin mutation. The clinical and genealogical findings in Bulgarian SPG4 patients suggest that a positive family history for inheritance as an autosomal-dominant trait is a strong indication for spastin mutation screening.

Adenosine Triphosphatases↗
PubMed2001

Assessment of the CASP4 fold recognition category.

We present the assessment of the CASP4 fold recognition category. The tasks we had to execute include the splitting of multidomain targets into single domains, the classification of target domains in terms of prediction categories, the numerical evaluation of predictions, the mapping of numerical scores to quality indices, the ranking of predictors, the selection of top-performing groups, and the analysis and critical discussion of the state of the art in this field. The 125 fold recognition groups were assessed by a total score that summarizes their performance over all targets and a quality score reflecting the average quality of the submitted models. Most of the top-performing groups achieved respectable results on both scores simultaneously. Several groups submitted models that were much closer to the respective target structures than any of the known folds in the Protein Data Bank. The CASP4 assessment included the automated servers of the parallel CAFASP experiment. For the total score, the highest rank achieved by a fully automated server is 12. Two thirds of the predictors have rather low scores.

Computer Simulation↗
PubMed2000

Structure-based evaluation of sequence comparison and fold recognition alignment accuracy.

The biological role, biochemical function, and structure of uncharacterized protein sequences is often inferred from their similarity to known proteins. A constant goal is to increase the reliability, sensitivity, and accuracy of alignment techniques to enable the detection of increasingly distant relationships. Development, tuning, and testing of these methods benefit from appropriate benchmarks for the assessment of alignment accuracy.Here, we describe a benchmark protocol to estimate sequence-to-sequence and sequence-to-structure alignment accuracy. The protocol consists of structurally related pairs of proteins and procedures to evaluate alignment accuracy over the whole set. The set of protein pairs covers all the currently known fold types. The benchmark is challenging in the sense that it consists of proteins lacking clear sequence similarity. Correct target alignments are derived from the three-dimensional structures of these pairs by rigid body superposition. An evaluation engine computes the accuracy of alignments obtained from a particular algorithm in terms of alignment shifts with respect to the structure derived alignments. Using this benchmark we estimate that the best results can be obtained from a combination of amino acid residue substitution matrices and knowledge-based potentials.

Algorithms↗
PubMed2000

Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration.

Evidence garnered from both human autopsy studies and genetic animal models has suggested a potential role for astrocytes in the pathogenesis of amyotrophic lateral sclerosis (ALS). Currently, mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) represent the only known cause of motoneuron loss in the disease, producing 21q linked familial ALS (FALS). To determine whether astrocytic dysfunction has a primary role in familial ALS, we have generated multiple lines of transgenic mice expressing G86R mutant SOD1 restricted to astrocytes. In GFAP-m SOD1 mice, astrocytes exhibit significant hypertrophy and increased GFAP reactivity as the animals mature. However, GFAP-mutant SOD1 transgenic mice develop normally and do not experience spontaneous motor deficits with increasing age. Histological examination of spinal cord in aged GFAP-mSOD1 mice reveals normal motoneuron and microglial morphology. These results indicate that 21q linked FALS is not a primary disorder of astrocytes, and that expression of mutant SOD1 restricted to astrocytes is not sufficient to cause motoneuron degeneration in vivo. Expression of mutant SOD1 in other cell types, most likely neurons, is critical for the initiation of disease.

Aging↗
PubMed2000

Effect of modification of light-harvesting complex II on fluorescence properties of thylakoid membranes of Arabidopsis thaliana.

The 77 K chlorophyll fluorescence spectra of Arabidopsis thaliana mutants deficient in lipid fatty acid desaturation have been used in order to further explore the influence of the modification of LHC II after mutation and proteolitic treatment on the energy transfer between the chlorophyll-protein complexes, as well as on the structure-function relationship in the supramolecular complex of Photosystem II. The gaussian decomposition and analysis of the fluorescence bands associated with PS II complex show the controversial action of the trypsin in the investigated thylakoid membranes. This reveals that the organization of PS II complexes is different in the wild type and both mutants indicating altered connection between the LHC II and the RC core complexes of PS II in both mutants. The results obtained demonstrate that different amounts of oligomer and monomer forms of LHC II in the mutants (LK3 and JB67), arising from lipid modification, are responsible for different proteolytic action in their thylakoid membranes.

Arabidopsis↗
PubMed2000

Polarized fluorescence spectroscopy of oriented isolated spinach Photosystem I particles.

The fluorescence anisotropy of Photosystem I (PS I) particles, isolated from spinach chloroplasts and containing approximately 200 chlorophyll molecules per reaction center, is investigated at low temperatures. The particles are oriented by squeezing in polyacrylamid gels with different macroscopic deformation parameters. Fluorescence anisotropy is measured upon steady state excitation with a laser line at 632.8 nm. A formula for the fluorescence anisotropy in oriented Photosystem I particles is applied for a different polarization of the linearly polarized exciting light. Our calculations are based on the consideration of the Photosystem I complex as a triple-chromophore complex: the absorbing chlorophyll molecules (chl), belonging to the light-harvesting complex of PS I (LHC), and two fluorophores, emitting at 720 nm (F720) and at 735 nm (F735), respectively. Using polarized fluorescence spectroscopy with a different polarization of the linearly polarized exciting light, the experimental dependence of the fluorescence anisotropy on this polarization is obtained. Based on this dependence and applying the derived formula, as a first approximation, both the orientation of the photosynthetic pigments with respect to the membrane and their mutual orientation are determined in PS I particles. As the most probable average orientational angles in PS I particles, we obtained the values 35 degrees / 50 degrees , 50 degrees / 60 degrees , and 65 degrees / 67 degrees for the absorbing dipoles of chl and for the emission dipoles of F720 and F735, respectively, with the normal of the plane of the membrane. For their mutual orientation, the following limits are determined: 10 degrees / 20 degrees , 40 +/- 2 degrees , 20 degrees / 30 degrees for the angles between chl and F720, chl and F735; and F720 and F735, correspondingly. Of course, the values of the angles estimated as a result of our study are an average value of all angles of the excited transitions and must be considered as their first approximation valid for the idealized case when all PS I particles are oriented in gel.

Journal Article↗
PubMed1994

Regulation of rDNA transcription in chloroplasts: promoter exclusion by constitutive repression.

Spinach chloroplasts contain two types of RNA polymerases. One is multimeric and Escherichia coli-like. The other one is not E. coli-like and might represent a monomeric enzyme of 110 kD. The quantitative relation of the two polymerases changes during plant development. This raises the question, how are plastid genes transcribed that contain E. coli-like and non-E. coli-like promoter elements during developmental phases when both enzymes are present? Transcription of the spinach plastid rrn operon promoter is initiated at three sites: P1, PC, and P2. P1 and P2 are preceded by E. coli-like promoter elements that are recognized by E. coli RNA polymerase in vitro. However, in vivo, transcription starts exclusively at PC. We analyzed different promoter constructions using in vitro transcription and gel mobility-shift studies to understand why P1 and P2 are not used in vivo. Our results suggest that the sequence-specific DNA-binding factor CDF2 functions as a repressor for transcription initiation of the E. coli-like enzyme at P1 and P2. We propose a mechanism of constitutive repression to keep the rrn operon in all developmental phases under the transcriptional control of the non-E. coli-like RNA polymerase.

Base Sequence↗