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Descending telencephalic information reaches longitudinal torus and cerebellum via the dorsal preglomerular nucleus in the teleost fish, Pantodon buchholzi: a case of neural preaptation?

The weakly electric mormyrids are known to have an ascending neuronal pathway that reaches the diencephalon and carries information concerned with electrolocation. The recipient diencephalic center, the dorsal preglomerular nucleus, receives a massive telencephalic input and projects to the corpus and valvula cerebelli. This circuitry has been interpreted as a uniquely derived (autapomorphic) feature for mormyrids. In the present study, we demonstrate with the fluorescent neuronal tracer DiI that the closely related, but non-electroreceptive, teleost Pantodon buchholzi possesses a dorsal preglomerular nucleus with similar telencephalo-cerebellar circuitry. The projection to the cerebellum only reaches the corpus, however, not the valvula cerebelli. Further, the dorsal preglomerular nucleus of Pantodon displays a descending pathway via the torus longitudinalis. Two phylogenetic interpretations for the presence of telencephalo-cerebellar pathways in both mormyrids and Pantodon are possible: if such a pathway existed as a preaptation in the common ancestor of mormyrids and Pantodon, it must be an exaptation for electroreception in mormyrids, since this sensory modality evolved anew in this teleost group; alternatively, the pathway evolved in parallel homoplasy, once in Pantodon, as part of a descending premotor pathway, and independently in mormyrids, where the system gains access to ascending electrosensory information.

Animals↗

Osteophyte evolution: studies in an experimental partial meniscectomy model.

Osteophytes are considered characteristic manifestations of osteoarthritis (OA) but may be seen independent of structural cartilage erosive lesions. Etiopathogenic mechanisms for osteophyte formation may involve responses to synovial inflammation, stretching of the synovial membrane, general mechanical instability, and vascular metaplasia. Experimentally induced OA following partial menisectomy in rabbits demonstrates active cellular replication at the normal joint periphery. Vascular responses are seen late in parallel with osteophyte formation rather than preceding it. Osteophyte ossification is primarily endochondral. The parallel stimulatory response to perichondrium, cartilage, and bone allows speculation on the interplay of mechanical/electrical forces and chemical/hormonal transducers in the development of osteophytes.

Adrenal Cortex Hormones↗

Evolution of the human brain: is bigger better?

1. The hominid brain has increased approximately three times in size since the Pliocene, but so has the brain of equids. The tripling of hominid brain size has been considered as an indicator of increased mental abilities, as it coincided with the production of tools, weapons and other artefacts of increasing sophistication. No indicators of the increase in equid intelligence are known. Intraspecific correlation between brain size and variously measured 'intelligence' is, in modern humans, very weak if not completely absent. With the exception of size, there are no major differences between the anatomy of ape and human brains. 2. A study of 297 estimates of body height, 626 estimates of bodyweight and 276 estimates of the cranial capacity of hominids dated at various periods over the past 5 million years shows that the increase in hominid brain size was paralleled by an increase in body size. 3. In a sample of 45 variously dated fossil hominids, brain size correlates isometrically with body size. 4. Since the Late Pleistocene (approximately 30,000 years ago), human brain size decreased by approximately 10%; yet again, this decrease was paralleled by a decrease in body size. 5. Therefore, it may be concluded that the gross anatomy of the hominid brain is not related to its functional capabilities. The large human brain:body size ratio may be a result of the structural reduction of the size of the gastrointestinal tract and, consequently, its musculoskeletal supports. It is related to richer, meat-based diets and extra-oral food processing rather than the exceptional increase in the size of the cerebrum. The exceptional mental abilities of humans may be a result of functional rather than anatomical evolution.

Animals↗

Ethylene evolution from tobacco leaves irradiated with UV-B.

Seedlings of Nicotiana tabacum L. (cv. Petit Havana SR1) were grown in the presence or absence of ultraviolet-B (UV-B, 290-320 nm) irradiation. The evolution of ethylene from the leaves, the content of 1-aminocyclopropane-1-carboxylic acid (ACC), an endogenous precursor of ethylene, and the activity of ACC synthase, a rate-limiting step in the production of ethylene, were increased by UV-B irradiation. The time course of these increases was parallel with the emergence of damage that was estimated by measuring the chlorophyll (Chl) content and the leakage of ions from leaf cells. Treatment of leaves with aminoethoxy-vinyl-glycine (AVG), a specific inhibitor of ACC synthase, reduced the extent of damage caused by UV-B. These results suggest that ethylene acts on certain processes to cause damage in tobacco leaves irradiated with UV-B.

Journal Article↗

Cloning and expression of SAG: a novel marker of cellular senescence.

Unlike immortalized cell lines, normal human fibroblasts in culture undergo replicative senescence in which the number of population doublings is limited. While fibroblasts display a variety of changes as they senesce in vitro, little is known about how gene expression varies as a function of population doubling level. We have used differential hybridization screening to identify human genes that are preferentially expressed in senescent cells. While we found several isolates that were up-regulated in late-passage cells, all appeared to be variants of the same cDNA, which we named senescence-associated gene (SAG). Our data show that SAG expression is threefold higher in senescent fibroblasts and closely parallels the progressive slowdown in growth potential, but is not cell-cycle regulated. Thus, SAG serves as an accurate marker for fibroblast growth potential during replicative senescence. Further studies demonstrated that SAG is a novel gene active in nearly all tissue types tested and that it is conserved through evolution. DNA sequencing data indicate that SAG contains a potential DNA-binding domain, suggesting that SAG may function as a regulatory protein.

Actins↗

Engineering tissues for in vitro applications.

Engineered tissues can be employed for studies on the fundamental mechanisms of embryology and adult physiology and for investigating the evolution of disease processes. They also provide platforms to evaluate the behavior of new chemical entities in drug development. The recent development of three specific technologies has greatly facilitated the engineering of tissues for in vitro applications: the microfabrication tools that serve to both define the cellular microenvironment and enable parallelization of cell-based assays; synthetic, tunable hydrogels to create three-dimensional microenvironments; and bioreactors to control nutrient transport and fluid shear stress. Furthermore, convergence of these tools is providing investigators with the opportunity to construct and study tissues in vitro with unprecedented levels of sophistication.

Animals↗

Directed enzyme evolution and selections for catalysis based on product formation.

Enzyme engineering by molecular modelling and site-directed mutagenesis can be remarkably efficient. Directed enzyme evolution appears as a more general strategy for the isolation of catalysts as it can be applied to most chemical reactions in aqueous solutions. Selections, as opposed to screening, allow the simultaneous analysis of protein properties for sets of up to about 10(14) different proteins. These approaches for the parallel processing of molecular information 'Is the protein a catalyst?' are reviewed here in the case of selections based on the formation of a specific reaction product. Several questions are addressed about in vivo and in vitro selections for catalysis reported in the literature. Can the selection system be extended to other types of enzymes? Does the selection control regio- and stereo-selectivity? Does the selection allow the isolation of enzymes with an efficient turnover? How should substrates be substituted or mimicked for the design of efficient selections while minimising the number of chemical synthesis steps? Engineering sections provide also some clues to design selections or to circumvent selection biases. A special emphasis is put on the comparison of in vivo and in vitro selections for catalysis.

Biotechnology↗

Local kinetic measures of macromolecular structure reveal partitioning among multiple parallel pathways from the earliest steps in the folding of a large RNA molecule.

At the heart of the RNA folding problem is the number, structures, and relationships among the intermediates that populate the folding pathways of most large RNA molecules. Unique insight into the structural dynamics of these intermediates can be gleaned from the time-dependent changes in local probes of macromolecular conformation (e.g. reports on individual nucleotide solvent accessibility offered by hydroxyl radical (()OH) footprinting). Local measures distributed around a macromolecule individually illuminate the ensemble of separate changes that constitute a folding reaction. Folding pathway reconstruction from a multitude of these individual measures is daunting due to the combinatorial explosion of possible kinetic models as the number of independent local measures increases. Fortunately, clustering of time progress curves sufficiently reduces the dimensionality of the data so as to make reconstruction computationally tractable. The most likely folding topology and intermediates can then be identified by exhaustively enumerating all possible kinetic models on a super-computer grid. The folding pathways and measures of the relative flux through them were determined for Mg(2+) and Na(+)-mediated folding of the Tetrahymena thermophila group I intron using this combined experimental and computational approach. The flux during Mg(2+)-mediated folding is divided among numerous parallel pathways. In contrast, the flux during the Na(+)-mediated reaction is predominantly restricted through three pathways, one of which is without detectable passage through intermediates. Under both conditions, the folding reaction is highly parallel with no single pathway accounting for more than 50% of the molecular flux. This suggests that RNA folding is non-sequential under a variety of different experimental conditions even at the earliest stages of folding. This study provides a template for the systematic analysis of the time-evolution of RNA structure from ensembles of local measures that will illuminate the chemical and physical characteristics of each step in the process. The applicability of this analysis approach to other macromolecules is discussed.

Animals↗

Structural characterization of the N-glycans of gp273, the ligand for sperm-egg interaction in the mollusc bivalve Unio elongatulus.

Gp273, a glycoprotein of the egg extracellular coats of the mollusc bivalve Unio elongatulus, is the ligand molecule for sperm-egg interaction during fertilization. In this study we have analyzed the N-glycans from gp273. N-glycans were enzymatically released by PNGase F digestion and their structures were elucidated by normal phase HPLC profiling of the 2-aminobenzamide-labeled N-glycans, MALDI-TOF mass spectrometry and 1H NMR spectroscopy. The combined data revealed that the N-glycans of gp273 consist of Glc1Man9GlcNAc2 and Man9GlcNAc2. In Unio, the presence of noncomplex-type N-glycans parallels the inefficacy of these glycans in the ligand function. Their role in the protection of the polypeptide chain from proteolytic attack is suggested by the electrophoretic patterns obtained after enzymatic digestion of the native and the N-deglycosylated protein. These results are discussed in the light of the evolution of the recognition and adhesion properties of oligosaccharide chains in the fertilization process.

Animals↗

Fast and stable method for simulating quantum electron dynamics

A fast and stable method is formulated to compute the time evolution of a wave function by numerically solving the time-dependent Schrodinger equation. This method is a real-space-real-time evolution method implemented by several computational techniques such as Suzuki's exponential product, Cayley's form, the finite differential method, and an operator named adhesive operator. This method conserves the norm of the wave function, manages periodic conditions and adaptive mesh refinement technique, and is suitable for vector- and parallel-type supercomputers. Applying this method to some simple electron dynamics, we confirmed the efficiency and accuracy of the method for simulating fast time-dependent quantum phenomena.

Journal Article↗

[Evolution of pollinization in France (2002)].

It was traditional until these last years to supervise the evolution of pollination by taking account only of the evolution of the number of grains of pollens present per m3 of air per year on each site. If this factor is significant, it is not sufficient. Indeed, it is essential to be able to supervise the evolution of the number of days in the year when the allergic risk related to a pollen is significant. The work which is presented shows over the years 1992 to 2002, for some sites of the RNSA (Amiens, Paris, Rouen, Strasbourg, Montlucon, Bordeaux, Lyon, Marseille, Toulouse) that there can be parallelism of the curves "pollinic counts" and "allergic risk", but also of light discordances. Should a thorough study of the dates of appearance supplement this work because these modifications can be the consequence of the climatic motions of these last decades.

Air↗

[Hydro-colloidal dressings which release hydro-active silver].

The study presented is a multicentric, prospective, open and comparative study designed with the objective of evaluating the performance of an antibacterial hydrocolloid dressing with hydroactivated silver (Comfeel Plata), when used to activate the healing process in wounds with high bacterial load, clinical signs of infection or malodour. Additionally, once the wound bed was appropriately prepared, a comparison in terms of efficacy was made between, on the one hand, continued treatment with the antibacterial hydrocolloid dressing, and, on the other hand, continued treatment with other dressings specifically designed for the proliferative phase of healing. Included into this study were 43 patients with chronic ulcers who were divided into two parallel treatment groups: In one group, Comfeel Plata (Coloplast AIS) was used until complete wound healing or for a maximum of 10-12 weeks, and in the second group Comfeel Plata (Coloplast A/S) was used until a clean wound bed was obtained and until the wound showed signs of positive evolution, at which moment the treatment was continued until complete healing or for a maximum of 10-12 weeks with dressings without silver designed especially for the proliferative phase of healing [Alione, Comfeel or Biatain (Coloplast AIS)]. The results obtained from the various study parameters indicate that the use of Comfeel Plata in the treatment of infected or colonized wounds prepares the wound bed and facilitates more rapid healing, and that the use of Comfeel Plata effectively reduces pain and malodour. The results indicate that once a clean wound bed is obtained, the use of a dressing without silver specifically for the proliferative phase will facilitate healing.

Bandages, Hydrocolloid↗

Crystal structure of adenylosuccinate synthetase from Escherichia coli. Evidence for convergent evolution of GTP-binding domains.

The structure of the P2(1) crystal form of adenylosuccinate synthetase from Escherichia coli has been determined to a resolution of 2.8 A. The refined model for the enzyme gives an R factor of 0.20 and a root-mean-square deviation from expected bond lengths and angles of 0.016 A and 2.27 degrees, respectively. The dominant structural element of each monomer of the homodimer is a central beta-sheet of 10 strands. The first nine strands of the sheet are mutually parallel with right-handed crossover connections between the strands. The 10th strand is antiparallel with respect to the first nine strands. In addition, the enzyme has two antiparallel beta-sheets, comprised of two strands and three strands each, 11 alpha-helices and two short 3/10-helices. The overall fold of the polypeptide chain has not been observed heretofore in any other protein structure. Residues tentatively assigned to the active site of the enzyme on the basis of chemical modification and directed mutation cluster in two separate regions. Gly12, Gly15, Gly17, Lys18, Ile19, and Lys331 lie at one end of a crevice that measures 12 A by 30 A by 12 A deep. Lys140 and Arg147 are not part of this crevice, but instead lie at the interface between monomers of the dimer. Lys140 makes a salt link with Asp231 of a monomer related by molecular symmetry and Arg147 binds to the carbonyl of the same Asp231. Superposition of the p21 ras protein (Pai, E. F., Kabsch, W., Krengel, U., Holmes, K., John, J., and Wittinghofer, A. (1989) Nature 341, 209-214) onto the synthetase reveals significant correspondences between side chains of the two proteins. Residues which interact with GTP in the p21ras protein have structurally equivalent residues in the synthetase. The GTP molecule, when transformed to the coordinate frame of the synthetase, falls into the crevice defined by studies in directed mutation. We suggest that the similarities in the GTP-binding domains of the synthetase and the p21ras protein are an example of convergent evolution of two distinct families of GTP-binding proteins.

Adenylosuccinate Synthase↗

Wnt gene expression in sea urchin development: heterochronies associated with the evolution of developmental mode.

The Wnt genes encode a large family of conserved secreted proteins that are widely involved in animal development. The variety and ubiquity of this ancient family suggest that Wnt genes may have been important in the evolution of animal development, including early development. To test this hypothesis, we have characterized the expression of several Wnt genes in closely related sea urchins that exhibit radically different modes of early development. Wnt-1, -4, and -5 genes exhibit several conserved molecular and developmental characteristics, both within sea urchins and with Wnt genes examined in other animals (Ferkowicz et al. 1998). Here, we demonstrate that sea urchin Wnt-5 transcripts are specifically detected by in situ hybridization in discrete embryonic, larval, and developing adult tissues and processes: (1) in a band of vegetal ectoderm in mesenchyme blastula stage embryos, (2) in the larval ciliary bands, (3) in tissues that form the early adult rudiment (left coelomic pouch and overlying vestibular ectoderm), and (4) in the developing adult radial nervous system. We find that the sites of Wnt-5 transcript accumulation are conserved in species exhibiting either indirect- or direct-developmental modes, suggesting that Wnt-5 function(s) have been conserved in sea urchin development. However, dramatic heterochronic changes in Wnt-5 gene expression have occurred in the direct-developing species that parallel the accelerated morphological changes that occur during direct development. These results suggest that heterochronic changes in the expression of conserved developmental regulatory genes, such as the Wnt family members, are agents of evolutionary change in animal development.

Animals↗

Non-traditional Alu evolution and primate genomic diversity.

Alu elements belonging to the previously identified "young" subfamilies are thought to have inserted in the human genome after the divergence of humans from non-human primates and therefore should not be present in non-human primate genomes. Polymerase chain reaction (PCR) based screening of over 500 Alu insertion loci resulted in the recovery of a few "young" Alu elements that also resided at orthologous positions in non-human primate genomes. Sequence analysis demonstrated these "young" Alu insertions represented gene conversion events of pre-existing ancient Alu elements or independent parallel insertions of older Alu elements in the same genomic region. The level of gene conversion between Alu elements suggests that it may have a significant influence on the single nucleotide diversity within the genome. All the instances of multiple independent Alu insertions within the same small genomic regions were recovered from the owl monkey genome, indicating a higher Alu amplification rate in owl monkeys relative to many other primates. This study suggests that the majority of Alu insertions in primate genomes are the products of unique evolutionary events.

Alu Elements↗

Gene transfer to the nucleus and the evolution of chloroplasts.

Photosynthetic eukaryotes, particularly unicellular forms, possess a fossil record that is either wrought with gaps or difficult to interpret, or both. Attempts to reconstruct their evolution have focused on plastid phylogeny, but were limited by the amount and type of phylogenetic information contained within single genes. Among the 210 different protein-coding genes contained in the completely sequenced chloroplast genomes from a glaucocystophyte, a rhodophyte, a diatom, a euglenophyte and five land plants, we have now identified the set of 45 common to each and to a cyanobacterial outgroup genome. Phylogenetic inference with an alignment of 11,039 amino-acid positions per genome indicates that this information is sufficient--but just rarely so--to identify the rooted nine-taxon topology. We mapped the process of gene loss from chloroplast genomes across the inferred tree and found that, surprisingly, independent parallel gene losses in multiple lineages outnumber phylogenetically unique losses by more that 4:1. We identified homologues of 44 different plastid-encoded proteins as functional nuclear genes of chloroplast origin, providing evidence for endosymbiotic gene transfer to the nucleus in plants.

Cell Nucleus↗

Use of phage display to probe the evolution of binding specificity and affinity in integrins.

The specific binding of RGD-containing proteins to integrin is a function of both the conformation of and the local sequence surrounding the RGD motif. To study the effect of these factors on integrin binding affinity and specificity, we obtained RGD-containing ligands specific for different integrins presented on the same protein scaffold. The beta-turn region between two anti-parallel beta-strands on the loop I of tendamistat, an inhibitor of alpha-amylase, was extended by two residues and randomized in a phagemid library. This library and two subsequently constructed RGD-containing loop I libraries were biopanned with purified integrins alphaIIbbeta3, alphaVbeta3 and alphaVbeta5 individually. The sequence analysis of selected tendamistat variants and characterization by phage ELISA revealed that phage adhesion is mediated exclusively by an RGD motif located at only two out of four possible positions on loop I. Further, sequences flanking the RGD motif were specific for different integrin targets. Interestingly, selected tendamistat variants mimic natural integrin ligands, both in sequence similarity and in integrin binding specificity, indicating that various ligand specificity patterns can be generated by driving towards maximum affinity in the integrin-ligand complexes.

Amino Acid Motifs↗

Evolution of the heart from bacteria to man.

This review provides an overview of the evolutionary path to the mammalian heart from the beginnings of life (about four billion years ago ) to the present. Essential tools for cellular homeostasis and for extracting and burning energy are still in use and essentially unchanged since the appearance of the eukaryotes. The primitive coelom, characteristic of early multicellular organisms ( approximately 800 million years ago), is lined by endoderm and is a passive receptacle for gas exchange, feeding, and sexual reproduction. The cells around this structure express genes homologous to NKX2.5/tinman, and gradual specialization of this "gastroderm" results in the appearance of mesoderm in the phylum Bilateria, which will produce the first primitive cardiac myocytes. Investment of the coelom by these mesodermal cells forms a "gastrovascular" structure. Further evolution of this structure in the bilaterian branches Ecdysoa (Drosophila) and Deuterostoma (amphioxus) culminate in a peristaltic tubular heart, without valves, without blood vessels or blood, but featuring a single layer of contracting mesoderm. The appearance of Chordata and subsequently the vertebrates is accompanied by a rapid structural diversification of this primitive linear heart: looping, unidirectional circulation, an enclosed vasculature, and the conduction system. A later innovation is the parallel circulation to the lungs, followed by the appearance of septa and the four-chambered heart in reptiles, birds, and mammals. With differentiation of the cardiac chambers, regional specialization of the proteins in the cardiac myocyte can be detected in the teleost fish and amphibians. In mammals, growth constraints are placed on the heart, presumably to accommodate the constraints of the body plan and the thoracic cavity, and adult cardiac myocytes lose the ability to re-enter the cell cycle on demand. Mammalian cardiac myocyte innervation betrays the ancient link between the heart, the gut, and reproduction: the vagus nerve controlling heart rate emanates from centers in the central nervous system regulating feeding and affective behavior.

Animals↗