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Molecular mimicry between protein and tRNA.

Mimicry is a sophisticated development in animals, fish, and plants that allows them to fool others by imitating a shape or color for diverse purposes, such as to prey, evade, lure, pollinate, or threaten. This is not restricted to the macro-world, but extends to the micro-world as molecular mimicry. Recent advances in structural and molecular biology uncovered a set of translation factors that resembles a tRNA shape and, in one case, even mimics a tRNA function for deciphering the genetic code. Nature must have evolved this art of molecular mimicry between protein and ribonucleic acid by using different protein structures until the translation factors sat in the cockpit of a ribosome machine, on behalf of tRNA, and achieved diverse actions. Structural, functional, and evolutionary aspects of molecular mimicry will be discussed.

Animals↗
PubMed1996

Enzymatic properties of transplanted glomerulosa cells.

There are several theories about the physiologic regeneration of adrenals and maintenance of physiologic steroid secretion after subtotal loss of adrenal cortical cells. According to the cell migration theory, adrenocytes from the zona glomerulosa migrate centripetally toward the medulla. This theory is opposed by the zonal theory according to which each zone resplenishes its cells independently. What these theories have in common is that they are based on data from the intact adrenal gland. We transplanted purified glomerulosa cells under the kidney's capsule of Lewis rats. The tissue was removed 30, 60, 90, and 150 days after transplantation to investigate the presence of two specific enzymes that are responsible for the secretion of aldosterone and corticosterone. Cytochrome p-450as is specific for glomerulosa cells producing aldosterone, and cytochrome p-45011beta is specific for fasciculata cells producing corticosterone. After sequencing the genetic code of these enzymes it became possible to demonstrate expression of the enzymes by in situ hybridization. The transplanted glomerulosa cells turned their enzymatic property to fasciculata cells expressing cytochrome p-45011beta. Our results suggest that glomerulosa cells are able to take over the physiologic function of a whole adrenal cortex in the absence of fasciculata cells, and that they are sufficient to maintain the function of the adrenal cortex.

Adrenal Medulla↗
PubMed1996

Evolutionary analysis of sea urchin mitochondrial tRNAs: folding of the molecules as suggested by the non-random occurrence of nucleotides.

Comparative analyses of the mitochondrial tRNA sequences of the sea urchins Arbacia lixula, Paracentrotus lividus and Strongylocentrotus purpuratus revealed that conserved nucleotides may be involved in determining the typical L-shaped spatial conformation of tRNAs. These results shed light on the specific tertiary interactions that allow the folding of the atypical mitochondrial tRNAs into a functional form. A consensus mitochondrial tRNA secondary structure was derived. It shows the presence of nucleotides virtually conserved only in these organisms that represent a sort of molecular signature in sea urchins and suggests a possible physiological role. Finally, we speculate that the non-canonical structure of animal tRNAs, as well as the deviations from the universality of the genetic code, may be due to the reduction in size of the metazoan mitochondrial genome, with the concomitant acquisition of new functions by the mitochondrial tRNAs.

Animals↗
PubMed2006

Imaging membrane potential in dendrites and axons of single neurons.

This review focuses on the use of imaging techniques to record electrical signaling in the fine processes of neurons such as dendrites and axons. Voltage imaging began with the use and development of externally applied voltage-sensitive dyes. With the introduction of internally applied dyes and advances in detection technology, it is now possible to record supra-threshold action potential responses, as well as sub-threshold synaptic potentials, in fine neuronal processes including dendritic spines. The development of genetically coded sensors, as well as variants of laser scanning microscopy such as second harmonic generation, offers promise for further advances in this field. Through the use and further development of these methods, optical imaging of membrane potential will continue to be a valuable tool for investigators wishing to explore the electrical events underlying single neuronal computation.

Action Potentials↗
PubMed2005

Heat-shock protein 70: molecular supertool?

The cellular stress response decreases cellular injury, either via primary induction of cytoresistance or by secondary enhancement of cellular repair mechanisms. The most frequently studied and best understood effectors of the cellular stress response are the heat shock proteins (HSP). HSP are among the oldest tools in the cellular protein machinery, demonstrating extremely high conservation of the genetic code since bacteria. Molecular chaperons, with the HSP-70 being the prototype, cooperate in transport and folding of proteins, preventing aggregation, and even resolubilizing injured proteins. Increasing evidence supports a role for HSP during the recovery from renal ischemia, in particular in cellular salvage from apoptotic cell death and cytoskeletal restoration. Recent studies also report the potential for biomolecular profiling of newborns for the risk of acute renal failure. In peritoneal dialysis novel data suggest the use of HSP expression for biocompatibility testing. More importantly, HSP are prime therapeutic candidates for clinical situations associated with predictable insults, such as organ procurement in transplant medicine and repetitive exposure to hyperosmolar and acidotic peritoneal dialysis fluids. The next challenge will be to define the regulatory pathways of the cellular stress response in these models to introduce novel therapeutic interventions, such as new pharmaceutics enhancing the HSP expression.

Animals↗
PubMed1998

Neurotrophic factors and the maldevelopmental hypothesis of schizophrenic psychoses. Review article.

The maldevelopmental model of schizophrenia postulates pathological alterations in embryonal neurogenesis as the etiopathogenetic basis of schizophrenic psychosis; the neurotrophic factor hypothesis explains these changes as the result of disturbances of processes involving the trophic factors. Neurotransmitter deficits are thereby interpreted as epiphenomena of underlying neurotrophic factor deficacy. The functional systems of the various neurotrophic factors are characterized by complex interaction mechanisms. Both primary genetic alterations, and secondary impairments, induced by exogene noxae, of the receptors and signal transducers associated with neurotrophic factors, as well as of the neurotrophic factors themselves are possible. Preliminary clinical studies indicate that schizophrenic psychoses may be associated with changes in the genetic code of certain neurotrophic factors. Various phenomena typical of the schizophrenic psychoses can be interpreted according to the neurotrophic factor hypothesis.

Animals↗
PubMed2026

Genome characterization of two novel mitoviruses and a negative-sense single-stranded RNA mycovirus from the phytopathogenic fungus Clarireedia jacksonii.

Clarireedia jacksonii is a phytopathogenic fungus responsible for dollar spot disease in turfgrass worldwide. In this study, we characterized the complete genome sequences of three novel mycoviruses isolated from C. jacksonii isolate MBCT-836 using next-generation sequencing and the fragmented and primer-ligated dsRNA sequencing (FLDS) method. Two of these viruses, designated Clarireedia jacksonii mitovirus 1 (CjMV1) and Clarireedia jacksonii mitovirus 2 (CjMV2), possess positive-sense single-stranded RNA genomes of 2,575 bp and 2,856 bp, respectively. Both viruses contain a single open reading frame that utilizes the mitochondrial genetic code and encodes an RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis placed CjMV1 and CjMV2 within the genera Unuamitovirus and Duamitovirus, respectively, in the family Mitoviridae. The third virus, Clarireedia jacksonii negative-stranded RNA virus 1 (CjNSV1), features a bisegmented negative-sense RNA genome consisting of a large segment (7,961 nt) encoding an RdRp with a conserved Bunya_RdRp domain, and a small segment (1,444 nt) encoding a protein showing homology to bunyavirus nucleocapsid proteins. Phylogenetic analysis revealed that CjNSV1 clusters with members of the proposed family Sclerobunyaviridae within the order Bunyavirales. To our knowledge, this study provides the first report of complete genome sequences of mycoviruses infecting C. jacksonii, expanding our understanding of the mycovirosphere in economically significant turfgrass pathogens.

Genome, Viral↗
PubMed2006

Ten years of bacterial genome sequencing: comparative-genomics-based discoveries.

It has been more than 10 years since the first bacterial genome sequence was published. Hundreds of bacterial genome sequences are now available for comparative genomics, and searching a given protein against more than a thousand genomes will soon be possible. The subject of this review will address a relatively straightforward question: "What have we learned from this vast amount of new genomic data?" Perhaps one of the most important lessons has been that genetic diversity, at the level of large-scale variation amongst even genomes of the same species, is far greater than was thought. The classical textbook view of evolution relying on the relatively slow accumulation of mutational events at the level of individual bases scattered throughout the genome has changed. One of the most obvious conclusions from examining the sequences from several hundred bacterial genomes is the enormous amount of diversity--even in different genomes from the same bacterial species. This diversity is generated by a variety of mechanisms, including mobile genetic elements and bacteriophages. An examination of the 20 Escherichia coli genomes sequenced so far dramatically illustrates this, with the genome size ranging from 4.6 to 5.5 Mbp; much of the variation appears to be of phage origin. This review also addresses mobile genetic elements, including pathogenicity islands and the structure of transposable elements. There are at least 20 different methods available to compare bacterial genomes. Metagenomics offers the chance to study genomic sequences found in ecosystems, including genomes of species that are difficult to culture. It has become clear that a genome sequence represents more than just a collection of gene sequences for an organism and that information concerning the environment and growth conditions for the organism are important for interpretation of the genomic data. The newly proposed Minimal Information about a Genome Sequence standard has been developed to obtain this information.

Bacterial Vaccines↗
PubMed2007

Analogy between language and biology: a functional approach.

We adopt here a functional approach to the classical comparison between language and biology. We first parallel events which have a functional signification in each domain, by matching the utterance of a sentence with the release of a protein. The meaning of a protein is then defined by analogy as "the constant contribution of the biochemical material composing the protein to the effects produced by any release of the protein". The proteome of an organism corresponds to an I-language (the idiolect of an individual), and the proteome of a species is equivalent to an E-language (a language in the common sense). Proteins and sentences are both characterized by a complex hierarchical structure, but the language property of 'double articulation' has no equivalent in the biological domain in this analogy, contrary to previous proposals centered on the genetic code. Besides, the same intimate relation between structure and meaning holds in both cases (syntactic structure for sentences and three-dimensional conformation for proteins). An important disanalogy comes from the combinatorial power of language which is not shared by the proteome as a whole, but it must be noted that the immune system possesses interesting properties in this respect. Regarding evolutionary aspects, the analogy still works to a certain extent. Languages and proteomes can be both considered as belonging to a general class of systems, that we call "productive self-reproductive systems", characterized by the presence of two dynamics: a fast dynamics in an external domain where functional events occur (productive aspect), and a slow dynamics responsible for the evolution of the system itself, driven by the feed-back of events related to the reproduction process.

Animals↗
PubMed1975

An electron microscopic study of the effects of portacaval shunts on the ultrastructure of the rat liver after partial hepatectomy.

The normally quiescent stable adult liver has a generous capacity for reparative hypertrophy and hyperplasia after loss of functional tissue. The large reserve of the liver's functional capacity permits survival of the animal even if over 70 per cent of its liver is removed. It retains an inherent capacity for regenerative growth which subsides once the original organ deficit is restored. This study attempted to resolve the question of whether alteration in hepatic hemodynamics affects the regenerative stimulus of the liver after partial (70 per cent) hepatectomy. It has shown that the liver remnant regenerates after reduction of portal blood flow by construction of a portacaval anastomosis. The diversion of blood from the liver exerts its own histologic and electron microscopic effects on the liver. Reduction of portal blood flow affects the temporal patterns of regeneration after partial hepatectomy but does not prevent completion of the regenerative process. Correlation of this study with the biochemical data available in the literature indicates that the structural changes in the cellular organelles during the process of regeneration reflect dynamic biochemical events that are based on a predetermined genetic code representing the key to life that is uniquely found in the liver.

Animals↗
PubMed1975

Phage T4 lysozyme. Physical properties and reversible unfolding.

Phage T4 lysozyme has been used extensively in studies of the genetic code. However, little work has been done on the characterization of the purified enzyme. Therefore, we determined the spectral properties of native T4 lysozyme and used these properties to follow the unfolding transition. The ultraviolet absorption spectrum and solvent perturbation difference spectrum indicate that the aromatic amino acids are extensively exposed to solvent. The CD and ORD spectra are characteristic of a high fraction of helix. Guanidine hydrochloride denaturation results show that over a T4 lysozyme concentration range of 0.07-1 g/l the c-m equals 2.7 M guanidine hydrochloride at pH 5 and that the transition is 100% reversible as judged by enzymatic assay and four different spectrophotometric criteria: CD at 295 nm, CD at 223 nm, fluorescence intensity at 350 nm and wavelength of maximum fluorescence. Guanidine hydrochloride denaturation at pH 2.5 was followed using fluorescence emission and has a c-m equals 1.7 M guanidine hydrochloride, indicating a strong pH dependence of chemical unfolding. Reversible thermal denaturation conditions were located at acid pH, 0.2 M NaCl, 10-4 M dithiothreitol and 10-6 M T4 lysozyme. The CD signal at 223 nm was used to measure the unfolding. Thermodynamic analysis of the thermal data showed an increase in T-m, increment H-unf and increment S-unf with increasing pH.

Binding Sites↗