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PubMed1977

The benign form of multiple sclerosis. Anatomo-clinical aspects.

The present paper is a study of three cases presenting the pathological aspect of chronic, non-evolutive multiple sclerosis, corresponding to a clinical picture of benign multiple sclerosis. The first case was discovered at autopsy, the second patient had two subclinical attacks of multiple sclerosis, with a twenty-year evolution (forme fruste), and in the third case the course of the chronic multiple sclerosis ran parallel to that of a cerebral and visceral arteriopathy. Anatomic study of the demyelinating lesions revealed their non-evolutive aspect and the presence within the plaques of lesions of the walls of small vessels with the perivascular adventitial fibrosis. The vascular changes appear to play a primordial role in the lack of evolution of the demyelinating areas, manifested clinically by a stationary, benign picture.

Brain↗

PubMed2005

Parallel capillary electrophoresis for the quantitative screening of fermentation broths containing natural products.

Directed molecular evolution is a recursive process of controlled genetic diversification and functional screening. The success of this approach is dependent on both the quality of the genetic diversity and the ability to accurately screen a large population of individual genetic variants for those having improved function. In this paper, the application of parallel capillary electrophoresis to rapidly quantitate lovastatin production levels by Aspergillus terreus mutants is described. A parallel 96 capillary instrument analyzed 900 samples in 8 h. with a 100 mM MES at pH 5.2 running buffer. In this manner, the fermentation broths of thousands of mutated strains were efficiently and inexpensively screened for increased lovastatin production. The ability to develop high-throughput methods to both separate and quantitate the components of complex mixtures greatly facilitates the ability to apply evolutionary engineering methods to complex biological systems.

Aspergillus↗

PubMed2006

Phytochrome-mediated development in land plants: red light sensing evolves to meet the challenges of changing light environments.

Phytochromes are photoreceptors that provide plants with circadian, seasonal, and positional information critical for the control of germination, seedling development, shade avoidance, reproduction, dormancy, and sleep movements. Phytochromes are unique among photoreceptors in their capacity to interconvert between a red-absorbing form (absorption maximum of approximately 660 nm) and a far-red absorbing form (absorption maximum of approximately 730 nm), which occur in a dynamic equilibrium within plant cells, corresponding to the proportions of red and far-red energy in ambient light. Because pigments in stems and leaves absorb wavelengths below about 700 nm, this provides plants with an elegant system for detecting their position relative to other plants, with which the plants compete for light. Certain aspects of phytochrome-mediated development outside of flowering plants are strikingly similar to those that have been characterized in Arabidopsis thaliana and other angiosperms. However, early diverging land plants have fewer distinct phytochrome gene lineages, suggesting that both diversification and subfunctionalization have been important in the evolution of the phytochrome gene family. There is evidence that subfunctionalization proceeded by the partitioning among paralogues of photosensory specificity, physiological response modes, and light-regulated gene expression and protein stability. Parallel events of duplication and functional divergence may have coincided with the evolution of canopy shade and the increasing complexity of the light environment. Within angiosperms, patterns of functional divergence are clade-specific and the roles of phytochromes in A. thaliana change across environments, attesting to the evolutionary flexibility and contemporaneous plasticity of phytochrome signalling in the control of development.

Arabidopsis↗

PubMed2005

Adaptive molecular evolution for 13,000 phage generations: a possible arms race.

Bacteriophage phiX174 was evolved on a continuous supply of sensitive hosts for 180 days ( approximately 13,000 phage generations). The average rate of nucleotide substitution was nearly 0.2% (11 substitutions)/20 days, and, surprisingly, substitutions accumulated in a clock-like manner throughout the study, except for a low rate during the first 20 days. Rates of silent and missense substitutions varied over time and among genes. Approximately 40% of the 71 missense changes and 25% of the 58 silent changes have been observed in previous adaptations; the rate of parallel substitution was highest in the early phase of the evolution, but 7% of the later changes had evolved in previous studies of much shorter duration. Several lines of evidence suggest that most of the changes were adaptive, even many of the silent substitutions. The sustained, high rate of adaptive evolution for 180 days defies a model of adaptation to a constant environment. We instead suggest that continuing molecular evolution reflects a potentially indefinite arms race, stemming from high levels of co-infection and the resulting conflict among genomes competing within the same cell.

Adaptation, Biological↗

PubMed2001

Evolutionary self-organization of cell-free genetic coding.

Genetic encoding provides a generic construction scheme for biomolecular functions. This paper addresses the key problem of coevolution and exploitation of the multiple components necessary to implement a replicable genetic encoding scheme. Extending earlier results on multicomponent replication, the necessity of spatial structure for the evolutionary stabilization of the genetic coding system is established. An individual-based stochastic model of interacting molecules in three-dimensional space is presented that allows the evolution of genetic coding to be analyzed explicitly. A massively parallel configurable computer (NGEN) is used to implement the model, on the time scale of millions of generations, directly in electronic hardware. The spatial correlations between components of the genetic coding system are analyzed and found to be essential for evolutionary stability.

Animals↗

PubMed1984

The effects of mono- and divalent salts on the O2-evolution activity and low temperature multiline EPR spectrum of Photosystem II preparations from spinach.

The ability of salts to inhibit the O2-evolution activity of PS II preparations is shown to parallel closely the Hofmeister series, suggesting that inhibition is related to the solubility of the 16, 24 and 33 kDa proteins in these salt solutions. An examination of the effect of salt inactivation on the low temperature multiline EPR signal indicates that the release of either the 16 and 24 kDa proteins, or additionally the 33 kDa protein blocks or greatly reduces the efficiency of the advancement of the water-splitting complex to the S2-state; under some conditions, this inhibition is reversible.

Electron Spin Resonance Spectroscopy↗

PubMed2005

Divergence of the mitochondrial electron transport chains from the green alga Chlamydomonas reinhardtii and its colorless close relative Polytomella sp.

Compelling evidence exists that the colorless algae of the genus Polytomella arose from a green Chlamydomonas-like ancestor by losing its functional photosynthetic apparatus. Due to the close relationship between the colorless and the green chlorophyte, Polytomella sp. appeared as a useful indicative framework for structural studies of Chlamydomonas reinhardtii mitochondria. However, comparative studies reported here unexpectedly revealed significant differences between the mitochondrial respiratory systems of the two algae. Two-dimensional blue native/SDS-PAGE of isolated mitochondria indicated that cytochrome-containing respiratory complexes III and IV in the two chlorophytes contrast in size, subunit composition and relative abundance. Complex IV in Polytomella is smaller than its counterpart in C. reinhardtii and occurs in two forms that differ presumably in the presence of subunit COXIII. The cytochrome c and the iron-sulfur Rieske protein of both chlorophytes revealed structural differences on the amino acid sequence level. Under comparable culture conditions, the colorless alga exhibits lower levels of cytochrome c and complex IV but a higher respiratory activity than the green alga. Cytochrome c levels were also found to be differently regulated by the growth conditions in both algae. The divergence between the respiratory systems in the two related chlorophytes can be viewed as a consequence of the loss of photosynthetic activity and/or of the adaptation to the environment via the acquisition of a more flexible, heterotrophic metabolism. Our understanding of mitochondrial function and evolution is expected to be greatly enhanced via further parallel studies of photosynthetic/non-photosynthetic algae, for which this study forms an incentive.

Amino Acid Sequence↗

PubMed2005

Systematics and health effects of chemically distinct tannins in medicinal plants.

The research began with an investigation of tannins from traditional medicinal plants and resulted in isolation and structure determination of hundreds of ellagitannins and dehydroellagitannins, as well as their oligomers and oxidized derivatives with various structures specific to each plant species. These polyphenols have been classified according to the stage of oxidative structural transformation and oligomerization, into types I-IV and I+ to IV+, etc. Parallels were found between their oxidative transformations and plant evolution. They were also classified by the linkage units between the monomers, into DOG, GOD, GOG and DOGOD types (D=Diphenoyl, G=Galloyl, O=Oxygen), etc. Besides their fundamental activities, e.g., reduction and anti-peroxidation properties, remarkable biological and pharmacological activities of various potencies have also been found, including, amongst others, inhibition of lipid-peroxidation, mutagenicity of carcinogens and tumor promotion, host-mediated antitumor effects specific to particular tannin structures, antiviral activity and potentiation of antibacterial activity.

Plants, Medicinal↗

PubMed2001

Mechanics and aerodynamics of insect flight control.

Insects have evolved sophisticated fight control mechanisms permitting a remarkable range of manoeuvres. Here, I present a qualitative analysis of insect flight control from the perspective of flight mechanics, drawing upon both the neurophysiology and biomechanics literatures. The current literature does not permit a formal, quantitative analysis of flight control, because the aerodynamic force systems that biologists have measured have rarely been complete and the position of the centre of gravity has only been recorded in a few studies. Treating the two best-known insect orders (Diptera and Orthoptera) separately from other insects, I discuss the control mechanisms of different insects in detail. Recent experimental studies suggest that the helicopter model of flight control proposed for Drosophila spp. may be better thought of as a facultative strategy for flight control, rather than the fixed (albeit selected) constraint that it is usually interpreted to be. On the other hand, the so-called 'constant-lift reaction' of locusts appears not to be a reflex for maintaining constant lift at varying angles of attack, as is usually assumed, but rather a mechanism to restore the insect to pitch equilibrium following a disturbance. Differences in the kinematic control mechanisms used by the various insect orders are related to differences in the arrangement of the wings, the construction of the flight motor and the unsteady mechanisms of lift production that are used. Since the evolution of insect flight control is likely to have paralleled the evolutionary refinement of these unsteady aerodynamic mechanisms, taxonomic differences in the kinematics of control could provide an assay of the relative importance of different unsteady mechanisms. Although the control kinematics vary widely between orders, the number of degrees of freedom that different insects can control will always be limited by the number of independent control inputs that they use. Control of the moments about all three axes (as used by most conventional aircraft) has only been proven for larger flies and dragonflies, but is likely to be widespread in insects given the number of independent control inputs available to them. Unlike in conventional aircraft, however, insects' control inputs are likely to be highly non-orthogonal, and this will tend to complicate the neural processing required to separate the various motions.

Animals↗

PubMed2000

Directed evolution of a stable scaffold for T-cell receptor engineering.

Here we have constructed a single-chain T-cell receptor (scTCR) scaffold with high stability and soluble expression efficiency by directed evolution and yeast surface display. We evolved scTCRs in parallel for either enhanced resistance to thermal denaturation at 46 degrees C, or improved intracellular processing at 37 degrees C, with essentially equivalent results. This indicates that the efficiency of the consecutive kinetic processes of membrane translocation, protein folding, quality control, and vesicular transport can be well predicted by the single thermodynamic parameter of thermal stability. Selected mutations were recombined to create an scTCR scaffold that was stable for over an hour at 65 degrees C, had solubility of over 4 mg ml(-1), and shake-flask expression levels of 7.5 mg l(-1), while retaining specific ligand binding to peptide-major histocompatibility complexes (pMHCs) and bacterial superantigen. These properties are comparable to those for stable single-chain antibodies, but are markedly improved over existing scTCR constructs. Availability of this scaffold allows engineering of high-affinity soluble scTCRs as antigen-specific antagonists of cell-mediated immunity. Moreover, yeast displaying the scTCR formed specific conjugates with antigen-presenting cells (APCs), which could allow development of novel cell-to-cell selection strategies for evolving scTCRs with improved binding to various pMHC ligands in situ.

Animals↗

PubMed2003

Controlled collisions for multi-particle entanglement of optically trapped atoms.

Entanglement lies at the heart of quantum mechanics, and in recent years has been identified as an essential resource for quantum information processing and computation. The experimentally challenging production of highly entangled multi-particle states is therefore important for investigating both fundamental physics and practical applications. Here we report the creation of highly entangled states of neutral atoms trapped in the periodic potential of an optical lattice. Controlled collisions between individual neighbouring atoms are used to realize an array of quantum gates, with massively parallel operation. We observe a coherent entangling-disentangling evolution in the many-body system, depending on the phase shift acquired during the collision between neighbouring atoms. Such dynamics are indicative of highly entangled many-body states; moreover, these are formed in a single operational step, independent of the size of the system.

Journal Article↗

PubMed1976

Acute renal failure of glomerular origin during visceral abscesses.

We studied 11 patients who had visceral abscesses and in whom acute renal failure developed. All renal biopsies showed a diffuse proliferative and crescentig glomerulonephritis. In seven patients blood cultures were repeatedly negative. Endocarditis could be ruled out in six patients. Seven patients had circulating cryoglobulins; serum complement levels were normal in seven and decreased in four; circulating immune complexes were found in the three patients studied. The evolution of the glomerulonephritis, documented by serial biopsies, closely paralleled the course of the infection. A complete recovery of renal function occurred in four cases in which a rapid and complete cure of the infection was obtained. Of five patients in whom the infection was not cured, four died, and chronic renal failure developed in one. In two patients in whom therapy was delayed, chronic renal failure also developed. Deep suppuration, even in the absence of bacteremia, may be responsible for a severe but possibly reversible glomerulonephritis with circulating immune complexes.

Abscess↗

PubMed2004

Advanced imaging in stone management.

PURPOSE OF REVIEW: Stone disease continues to plague humankind. Recent innovations in minimally invasive surgery, however, have decreased morbidity for the treatment of lithiasis, once only amenable to open surgical techniques. These advances in stone management have also been paralleled in the radiographic armamentarium. Herein, we describe the evolution of initial radiographic workup for urolithiasis, from abdominal radiograph to three-dimensional computed tomography and some of the novel applications thereof. RECENT FINDINGS: Previously, abdominal radiography was the only modality available for the visualization of calculi. Subsequently, the development of intravenous contrast aided in evaluating renal function, detecting the presence and location of obstruction, and in identifying filling defects. Most recently, prospective randomized trials have demonstrated improved sensitivity and specificity using noncontrast helical computed tomography rather than intravenous pyelogram with regard to the initial evaluation of acute flank pain. Further attempts to lower the overall radiation dose without compromising efficacy have also been introduced. Currently, the volume of calculus disease can be better quantified and somewhat qualified from three-dimensional computer software, thereby optimizing stone management. SUMMARY: Considerable progress has been made using minimally invasive techniques in the treatment of nephrolithiasis. Furthermore, advances in radiographic computer hard- and software applications allow for a rapid acquisition time and improved image quality without sacrificing diagnostic accuracy. In time, it is likely that the combination of these enhanced imaging modalities will lead to an improvement in stone localization, fragmentation and stone-free rates.

Acute Disease↗

PubMed2003

Field fluctuation spectroscopy in a reverberant cavity with moving scatterers.

We report a study of transient ultrasonic waves inside a reverberant cavity containing moving scatterers. We show that the elastic mean free path and the dynamics of the scatterers govern the evolution of the autocorrelation of acoustic wave field. A parallel is established between these results and a closely related technique, diffusing acoustic wave spectroscopy. Excellent agreement is found between experiment and theory for a moving stainless steel ball in a water tank, thereby elucidating the underlying physics, and a potential application, fish monitoring inside aquariums, is demonstrated.

Journal Article↗

PubMed2006

Phylogenetic analysis of Culicoides species from France based on nuclear ITS1-rDNA sequences.

Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) play important roles in the transmission of viral diseases affecting wild and domestic ruminants and horses, including Bluetongue (BT) and African horse sickness (AHS) respectively. In southern Europe, BT has been largely transmitted by the classical Afro-Asian vector Culicoides imicola Kieffer. However, other species such as C. obsoletus Meigen, C. scoticus Downs & Kettle and C. pulicaris Linné may also be involved in BTV transmission. As a consequence of the discovery of C. imicola followed by BTV-2 outbreaks on the island of Corsica in October 2000, further studies on these biting midges have been carried out. To better characterize the evolution and phylogenetic relations of Culicoides, molecular analysis in parallel with a morphology-based taxonomic approach were performed. Phylogenetic analyses of French Culicoides species were undertaken using the ribosomal DNA (rDNA) internal transcribed spacer 1 (ITS1) as a molecular target. This region was shown to be useful in understanding evolutionary and genetic relationships between species. Construction of several trees showed that molecular phylogeny within the genus Culicoides correlates not only with morphological-based taxonomy but also with ecological patterns.

Animals↗

PubMed1986

Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS.

In a study of genetic variation in the AIDS virus, HTLV-III/LAV, sequential virus isolates from persistently infected individuals were examined by Southern blot genomic analysis, molecular cloning, and nucleotide sequencing. Four to six virus isolates were obtained from each of three individuals over a 1-year or 2-year period. Changes were detected throughout the viral genomes and consisted of isolated and clustered nucleotide point mutations as well as short deletions or insertions. Results from genomic restriction mapping and nucleotide sequence comparisons indicated that viruses isolated sequentially had evolved in parallel from a common progenitor virus. The rate of evolution of HTLV-III/LAV was estimated to be at least 10(-3) nucleotide substitutions per site per year for the env gene and 10(-4) for the gag gene, values a millionfold greater than for most DNA genomes. Despite this relatively rapid rate of sequence divergence, virus isolates from any one patient were all much more related to each other than to viruses from other individuals. In view of the substantial heterogeneity among most independent HTLV-III/LAV isolates, the repeated isolation from a given individual of only highly related viruses raises the possibility that some type of interference mechanism may prevent simultaneous infection by more than one major genotypic form of the virus.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Antigenic analysis of equine infectious anemia virus (EIAV) variants by using monoclonal antibodies: epitopes of glycoprotein gp90 of EIAV stimulate neutralizing antibodies.

Monoclonal antibodies produced against the prototype cell-adapted Wyoming strain of equine infectious anemia virus (EIAV), a lentivirus, were studied for reactivity with the homologous prototype and 16 heterologous isolates. Eighteen hybridomas producing monoclonal antibodies (MAbs) were isolated. Western blot (immunoblot) analyses indicated that 10 were specific for the major envelope glycoprotein (gp90) and 8 for the transmembrane glycoprotein (gp45). Four MAbs specific to epitopes of gp90 neutralized prototype EIAV infectivity. These neutralizing MAbs apparently reacted with variable regions of the envelope gp90, as evidenced by their unique reactivity with the panel of isolates, suggesting recognition of at least three different neutralization epitopes. The conformation of these epitopes appears to be continuous, as they resisted treatment with sodium dodecyl sulfate and reducing reagents. Monoclonal antibodies that reacted with conserved epitopes on gp90 or gp45 failed to neutralize EIAV. Our data also demonstrated that there was a large spectrum of possible EIAV serotypes and confirmed that antigenic variation occurs with high frequency in EIAV. Moreover, the data showed that variation is a rapid and random process, as no pattern of variant evolution was evident by comparison of 13 isolates from parallel infections. These results represent the first production of neutralizing MAbs specific for a lentivirus glycoprotein and document alterations in one or more neutralization epitopes of the major surface glycoprotein among sequential isolates of EIAV recovered during persistent infection.

Animals↗

PubMed1976

The tuberous sclerosis syndrome: clinical and EEG studies in 100 children.

The evolution of the early clinical and EEG features in 100 children who developed the tuberous sclerosis syndrome is discussed with particular emphasis on individual variability of epileptic manifestations, skin changes, and mental defect. There were 61 boys and 39 girls. Seizures of various kinds occurred in 98 and in the first 2 years of life infantile spasms were a prominent feature (69) with a partial overlap of other kind of seizures (75). Mental defect (88) and poorly pigmented areas of the skin (77) were already detectable in the first 1 to 2 years of life, while fibroangioma of the face (adenoma sebaceum) (77) and intracranial calcifications (35) became increasingly apparent after the age of 2 to 4 years. The EEG abnormalities tended to be gross in the first 2 years of life, but their subsequent evolution was towards multifocal alterations and some areas of relatively better preserved rhythmic activity. The evolution of the various skin lesions did not run parallel either with that of the clinically detectable seizures or with the appearance of intracranial calcifications.

Adenoma↗