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At least 1,783 records · Page 99Linked to original sources
PubMed1998

7-Methylguanosine at the anticodon wobble position of squid mitochondrial tRNA(Ser)GCU: molecular basis for assignment of AGA/AGG codons as serine in invertebrate mitochondria.

In mitochondria of the squid, Loligo bleekeri, both the AGA and AGG codons are considered to correspond to serine instead of arginine as in the universal genetic code, and its genome encodes a single tRNA(Ser) gene with the anticodon GCT. Therefore, this gene product, tRNA(Ser)GCU, should be able to translate all four AGN (N; U, C, A, and G) codons as serine. To elucidate this recognition mechanism, the tRNA(Ser)GCU was isolated from squid liver and its complete nucleotide sequence determined. The tRNA(Ser)GCU was found to possess 7-methylguanosine (m7G) at the wobble position of the anticodon. This suggests that in the squid mitochondrial system, tRNA(Ser)GCU with the anticodon m7GCU can recognize not only the usual serine codons AGU and AGC, but also the unusual serine codons AGA and AGG, as in the case of starfish mitochondria (Matsuyama et al., J. Biol Chem. 273 (1988) 3363-3368).

Animals↗
PubMedDate not supplied

The biological waste product formation in the light of the membrane hypothesis of aging.

The membrane hypothesis of aging (MHA) explains the biological waste product (lipofuscin) formation as a disbalance between the rates of protein synthesis and damage, as well as of elimination of the damaged components. Although, this concept has not been refuted on the basis of any experimental evidence, it has neither been widely accepted. During the last decade the general interest has turned toward the molecular genetics so intensely, that research aimed at clarifying cell biological mechanisms became so to say hibernated. Nowadays it is being recognized more and more that after the complete description of the human genetic code, attention has to be dedicated again to the cellular mechanisms explaining the function of the gene products (proteins). In this context, our experimental findings described during the recent years may become again the subject of interest. We have shown that the in vivo inhibition of the lysosomal thiol-proteinase functions by sublethal doses of leupeptin in young, adult and old mice results in a considerable increase (about 30%) of the immobile fraction of membrane proteins in hepatocyte plasma membrane, meanwhile the lateral diffusion constant of the still mobile membrane proteins increased. These observations were interpreted as signs of a general slowing down of protein turnover in the plasma membrane, just by inhibiting the elimination mechanisms in the lysosomes. This paper will discuss the theoretical conclusions and significance of these findings for the biological waste product formation, as a basic cell biological function.

Journal Article↗
PubMed2000

Tick-borne encephalitis virus strains of Western Siberia.

Tick-borne encephalitis virus (TBEV) strains were isolated from ticks in Western Siberia for 12 years. Molecular hybridization of the 46 viral RNA with the TBEV cDNA and oligonucleotide probes revealed differences between the Siberian and Far Eastern strains. A comparison of the viral E gene fragment nucleotide sequence showed 89-98% homology between Siberian TBEV strains, whereas their similarity with strains from other populations was less than 83%. However, the viral E and NS1 glycoprotein antigenic structures appeared to be conservative because of the degenerate genetic code. This was shown by enzyme-linked immunosorbent assay with the corresponding monoclonal antibodies (MAb). The single exception was the MAb 17C3 against nonstructural glycoprotein NS1, which could distinguish Siberian from Far Eastern strains. Moreover, the neurovirulence differed between strains from the two natural populations. Lower neuroinvasiveness of the Siberian strains in comparison with Far Eastern Sofyin strain might be caused by both E and NS1 glycoprotein mutations.

Animals↗
PubMed1999

Neurotensin-SPDP-poly-L-lysine conjugate: a nonviral vector for targeted gene delivery to neural cells.

We report herein the synthesis of a novel DNA delivery system and in vitro evidence of its ability to transfect cell lines by binding to the high-affinity neurotensin receptor and subsequent internalization of ligand-receptor complexes. The targeting vehicle consisted of neurotensin crosslinked with poly-L-lysine via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP). The SPDP-derivatives with either neurotensin or poly-L-lysine were purified by gel filtration. The conjugate resulting of the reaction of neurotensin-SPDP with HS-SPDP-poly-L-lysine was purified through Biogel A 1.5. The neurotensin-SPDP-poly-L-lysine conjugate was able to bind plasmidic DNAs (pSV2cat and pGreen Lantern-1) at optimal molar ratios of 1:5 and 1:6 (DNA: conjugate), respectively. The conjugate internalized those plasmids in the cell lines (N1E-115 and HT-29) bearing the high-affinity neurotensin receptor. Expression of the plasmid products, chloramphenicol acetyltransferase and green fluorescent protein, was observed in such cell lines. Both internalization and expression of the plasmids transferred by the neurotensin-SPDP-poly-L-lysine conjugate were prevented by neurotensin (1 microM) and SR-48692 (100 nM), a specific antagonist of the high-affinity neurotensin receptor. The neurotensin-SPDP-poly-L-lysine conjugate was unable to transfect cell lines lacking the neurotensin receptor (COS-7 and L-929). In rat brain, the high-affinity neurotensin receptor is expressed by specific neurons such as those of the nigrostriatal and mesolimbic dopaminergic systems. Therefore, the neurotensin-SPDP-poly-L-lysine conjugate could be a useful tool for gene delivery to those neuronal systems.

Animals↗
PubMed2000

Rare genomic changes as a tool for phylogenetics.

DNA sequence data have offered valuable insights into the relationships between living organisms. However, most phylogenetic analyses of DNA sequences rely primarily on single nucleotide substitutions, which might not be perfect phylogenetic markers. Rare genomic changes (RGCs), such as intron indels, retroposon integrations, signature sequences, mitochondrial and chloroplast gene order changes, gene duplications and genetic code changes, provide a suite of complementary markers with enormous potential for molecular systematics. Recent exploitation of RGCs has already started to yield exciting phylogenetic information.

Journal Article↗
PubMed2003

Pharmacogenomics of psychiatric drug treatment.

It is the goal of pharmacogenomics in psychiatry to establish predictive relationships between polymorphisms of candidate genes and therapeutic response to drug treatment. Polymorphisms of candidate genes related to drug mechanisms and pathophysiology of illness and defined clinical phenotype are the foundations for pharmacogenomic studies. Pharmacogenomic studies of antipsychotic response have focused on polymorphisms of genes for dopamine and serotonin receptors with most positive results reported for polymorphisms of genes of the 5HT2a and 5HT2c serotonin receptor subtypes. Although the goal of establishing individualized medicine predicated on an individual patient's genetic code has yet to be achieved, the fundamentals are now in place for second-generation investigation and more application to health care.

Clinical Trials as Topic↗
PubMed1998

Antisense homology box-derived peptides represent a new class of endothelin receptor inhibitors.

Several peptides encoded by the sense and corresponding antisense DNA have been found to recognize and bind to each other. We developed software to search for sense-antisense regions within proteins taking into account the degeneracy of the genetic code, i.e., one amino acid can have several "antisense" counterparts. Using this approach, we searched endothelin receptor type A for intramolecular regions related in sense-antisense fashion. After locating these regions (termed "antisense homology boxes"), several corresponding peptides were synthesized. The four new ET(A) receptor fragment peptides ETR-P1 ("CALSVDRYRAVASW"), ETR-P3 ("QGIGPLITAIEI"), ETR-P4 ("IADNAERYSANLSSHV") and ETR-P6 ("LNRRNGSLRIALSEHLKNRREVA") reported here can inhibit ET-1 activity.

3T3 Cells↗
PubMed1999

Specificity of anti-Nef antibodies produced in mice immunized with DNA encoding the HIV-1 nef gene product.

Mice immunized with plasmid DNA encoding Nef regulatory protein of human immunodeficiency virus type 1 developed high levels of anti-Nef antibodies. After 4 intramuscular injections of 100 microg plasmid DNA, anti-Nef antibodies reached titers up to 2 x 10(4). A significant specific antibody response was maintained for at least 16 months. Using a set of seven 31-66 mer synthetic peptides covering the entire sequence of Nef, we analysed the specificity of ant-Nef antibodies. Interestingly, specific antibodies produced in response to Nef expressing plasmid DNA did not recognize the linear peptides except the long C-terminal peptide (aa 141-205) for 3 of the 10 sera. With anti-Nef antibodies produced in mice immunized with the protein Nef without any adjuvant, the same restraint epitope binding was found. Only 3 of the 5 Nef positive sera reacted with the C-terminal peptide. This suggests that specific antibodies induced by plasmid DNA as well as by the non-denatured protein recognize conformation-dependent epitopes. On the contrary, anti-Nef antibodies from mice immunized with the protein in Freund's adjuvant showed a broader epitope reactivity pattern. Interestingly, the analysis of immunoglobulin isotype profiles of antibodies generated by the different protocols of immunization showed that plasmid DNA immunization induced predominantly IgG2a, whereas immunization with Nef protein, with or without adjuvant, yielded a preponderance of IgG1 antibodies.

Amino Acid Sequence↗
PubMed1997

Graphs in sequence spaces: a review of statistical geometry.

Statistical geometry is a method of comparative sequence analysis of genes. Based on the concept of the sequence space of nucleic acids it computes the geometries of sequence sets, mainly quartets, by combining both the vertical and horizontal information content of the sequences. The geometries can be used to deduce, for example, the degree of tree-likeness of the data set without any a priori assumption of an evolution model. Furthermore, statistical geometry allows to detect varying positional substitution rates in sequences. Applications of the method to tRNA sequences have provided an assessment for the age of the genetic code. Furthermore, applications of statistical geometry to homeoboxes as well as different virus families have helped to assign reliable kinship relationships. In addition, a lower bound for the age of the common ancestor of the human and simian immunodeficiency viruses has been established.

DNA, Viral↗
PubMedDate not supplied

Symbols and dynamics in the brain.

The work of physicist and theoretical biologist Howard Pattee has focused on the roles that symbols and dynamics play in biological systems. Symbols, as discrete functional switching-states, are seen at the heart of all biological systems in the form of genetic codes, and at the core of all neural systems in the form of informational mechanisms that switch behavior. They also appear in one form or another in all epistemic systems, from informational processes embedded in primitive organisms to individual human beings to public scientific models. Over its course, Pattee's work has explored (1) the physical basis of informational functions (dynamical vs. rule-based descriptions, switching mechanisms, memory, symbols), (2) the functional organization of the observer (measurement, computation), (3) the means by which information can be embedded in biological organisms for purposes of self-construction and representation (as codes, modeling relations, memory, symbols), and (4) the processes by which new structures and functions can emerge over time. We discuss how these concepts can be applied to a high-level understanding of the brain. Biological organisms constantly reproduce themselves as well as their relations with their environs. The brain similarly can be seen as a self-producing, self-regenerating neural signaling system and as an adaptive informational system that interacts with its surrounds in order to steer behavior.

Animals↗
PubMed2003

On the physics of the symbol--matter problem in biological systems and the origin of life: affine Hilbert spaces model of the robustness of the internal quantum dynamics of biological systems.

In the present paper, some physical considerations of the biological symbol-matter problem is exposed. First of all, the physical concept of quantum dynamical internal measuremental robustness is discussed. In this context, the significance of introducing affine molecular Hilbert spaces, the original (primordeal) internal quantum measurement, and the global constraining nature of time-inversion symmetry restoring, as a special restoration force, is discussed at some length. It is pointed out, as a summary, that global robustness of the internal dynamics of quantum measurements is due to two basic factors: on one hand, the global constraining nature of the chosen specific (symmetry-) restoring force, and on the other, the individual robustness of the discrete local internal measuremental interactions. The second condition is supposed to follow from a system-internalised ("objective") Bohr-type Copenhagen interpretation of quantum mechanics, corresponding, in an external context, to the Generalized Complementarity Principle of Bohr and Elsasser. It is not claimed, however, that this latter problem has been, as yet, satisfactorily settled physically. In fact, if it were, it would amount to a specifically biological quantum theory of internal measurement, which had to be rooted in the original primordeal global internal measurement, amounting to the origin of the genetic code.

Adaptation, Physiological↗
PubMed2004

What does a molecule want? The myth of the self-replicating molecule (comments on the "selfish-gene" paradigm).

The non-equilibrium statistical mechanical autocatalytic theory, underlying the "selfish-gene" paradigm, is shown to be at several points insufficient and contradictory for the description of observed facts of biological systems. We analyze at some length these deficiencies as (1) statistical versus individual non-linear self-constraints, (2) the continuous versus discrete cause-effect evolutional transition, and (3) the nature of the emerging aim-directed biological systems. Concerning the latter, it is shown that it can only be described with reference to the origin of the genetic code, which cannot be accounted for by the continuous evolution of non-equilibrium statistical mechanical systems. We point out that these deficiencies might be covered by alternative (quantum) theoretical considerations. The theory of evolution according to which may have lead to aim-directedness in the primordeal times in a more consistent way, concerning both phenotype and genotype. The specific physical model adopted is an affine Hilbert spaces scheme, with a naturally emerging internal dynamics of measurement, monitored internally by (time-inversion) symmetry restoration. In this context, the physical relation of internal molecular symbolism (semiosis) and internal quantum mechanics is discussed.

Catalytic Domain↗
PubMed2001

The scanning near-field optical microscope as a tool for proteomics.

The identification of the entire genetic code of human DNA is more or less completed. With this knowledge, research in identifying the real information lying in the genes, will begin. This information is contained in the proteins, which are the main biological actors in the cell. For this reason proteins will be targeted in biological investigations in the future. The structure, affinity and reactivity of each identified protein has to be determined, which is a primary goal in the field of proteomics. This will require new and better strategies to identify protein-protein interaction. Our approach, based on the detection and visualization of single proteins by scanning near-field optical microscopy (SNOM), has allowed us to visualize various fixed and fluorochrome-labelled proteins at the nanometer scale. Subsequently SNOM may then be developed to efficiently detect the specific behavior of a certain protein in response to other biomolecules.

Bacterial Proteins↗
PubMed1998

Pathogenicity and immunogenicity of different isolates of Teladorsagia circumcincta.

The effects on liveweight gain and development of immunity were studied in lambs trickle infected for 8 weeks with either a benzimidazole-resistant isolate (Moredun ovine resistant isolate, MORI), a multiple benzimidazole + ivermectin-resistant isolate (Moredun caprine resistant isolate, MCRI) or an unselected susceptible isolate (Moredun ovine susceptible isolate, MOSI) of Teladorsagia circumcincta. Plasma pepsinogen concentrations of infected groups were significantly elevated compared to an uninfected control group (P < 0.001) by day 14. The liveweight gains varied markedly but there were no statistical differences between the infected and uninfected control groups at any point in time during the study. Lambs infected with the MORI had significantly lower faecal consistency scores than the other challenged groups on days 7 and 14 (P < 0.05) but from day 21 onwards, faecal consistencies were similar in all of the groups. There was a notable difference in the pre-patent periods of the different isolates with the MOSI producing positive faecal egg counts (FECs) by day 14 of the study. The FECs remained reasonably low once infections had reached patency and there were no further differences between the groups. Following administration of anthelmintic to remove residual worms from the trickle infection, no differences between the infected groups in terms of worm burden or mucosal mast cell numbers were evident as a consequence of a single challenge infection. The changes in genetic code associated with enhanced resistance against anthelmintics do not appear to have resulted in any fundamental alteration of the pathogenicity and immunogenicity of these three isolates of Teladorsagia.

Animals↗
PubMed2001

The Candida albicans gene encoding the cytoplasmic leucyl-tRNA synthetase: implications for the evolution of CUG codon reassignment.

In a number of Candida species the 'universal' leucine codon CUG is decoded as serine. To help understand the evolution of such a codon reassignment we have analyzed the Candida albicans leucyl-tRNA synthetase (CaLeuRS) gene (CaCDC60). The predicted CaLeuRS sequence shows a significant level of amino acid identity to LeuRS from other organisms. A mitochondrial LeuRS (ScNAM2) homologue, which shared low identity with the CaLeuRS, was also identified in C. albicans. Antigenically-related LeuRSs were identified in a range of Candida species decoding the CUG codon as both serine and leucine, using an antibody raised against the N-terminal 15 amino acids of the CaLeuRS. Complementation experiments demonstrated that the CaLeuRS was able to functionally complement a Saccharomyces cerevisiae cdc60::kanMX null mutation. We conclude that there is no alteration in tRNA recognition and aminoacylation by the C. albicans LeuRS, which argues against it having a role in codon reassignment. The nucleotide sequences of the CaCDC60 and CaNAM2 genes were deposited at GenBank under Accession numbers AF293346 and AF352020, respectively.

Amino Acid Sequence↗
PubMed2002

Mitochondrial DNA in metazoa: degree of freedom in a frozen event.

The mitochondrial genome (mtDNA), due to its peculiar features such as exclusive presence of orthologous genes, uniparental inheritance, lack of recombination, small size and constant gene content, certainly represents a major model system in studies on evolutionary genomics in metazoan. In 800 million years of evolution the gene content of metazoan mitochondrial genomes has remained practically frozen but several evolutionary processes have taken place. These processes, reviewed here, include rearrangements of gene order, changes in base composition and arising of compositional asymmetry between the two strands, variations in the genetic code and evolution of codon usage, lineage-specific nucleotide substitution rates and evolutionary patterns of mtDNA control regions.

Animals↗
PubMed2003

mRNA 5' region sequence incompleteness: a potential source of systematic errors in translation initiation codon assignment in human mRNAs.

The amino acid sequence of gene products is routinely deduced from the nucleotide sequence of the relative cloned cDNA, according to the rules for recognition of start codon (first-AUG rule, optimal sequence context) and the genetic code. From this prediction stem most subsequent types of product analysis, although all standard methods for cDNA cloning are affected by a potential inability to effectively clone the 5' region of mRNA. Revision by bioinformatics and cloning methods of 109 known genes located on human chromosome 21 (HC 21) shows that 60 mRNAs lack any in-frame stop upstream of the first-AUG, and that in five cases (DSCR1, KIAA0184, KIAA0539, SON, and TFF3) the coding region at the 5' end was incompletely characterized in the original descriptions. We describe the respective consequences for genomic annotation, domain and ortholog identification, and functional experiments design. We have also analyzed the sequences of 13,124 human mRNAs (RefSeq databank), discovering that in 6448 cases (49%), an in-frame stop codon is present upstream of the initiation codon, while in the other 6676 mRNAs (51%), identification of additional bases at the mRNA 5' region could well reveal some new upstream in-frame AUG codons in the optimal context. Proportionally to the HC 21 data, about 550 known human genes might thus be affected by this 5' end mRNA artifact.

5' Untranslated Regions↗