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A group-I intron in the mitochondrial small subunit ribosomal RNA gene of Sclerotinia sclerotiorum.

A 1,380-bp intervening sequence within the mitochondrial small subunit ribosomal RNA (mt SSU rRNA) gene of the fungus Sclerotinia sclerotiorum has been sequenced and identified as a group-I intron. This is the first report of an intron in the mt SSU rRNA gene. The intron shows close similarity in secondary structure to the subgroup-IC2 introns from Podospora (ND3i1, ND5i2, and COIi5) and Neurospora (ND5i1). The intron has an open reading frame (ORF) that encodes a putative protein of 420 amino acids which contains two copies of the LAGLI-DADG motif. The ORF belongs to a family of ORFs identified in Podospora (ND3i1, ND4Li1, ND4Li2, ND5i2, and COIi5) and Neurospora (ND5i1). The putative 420-aa polypeptide is also similar to a site-specific endonuclease in the chloroplast large subunit ribosomal RNA (LSU rRNA) gene of the green alga Chlamydomonas eugametos. In each clone of S. sclerotiorum examined, including several clones which were sampled over a 3-year period from geographically separated sites, all isolates either had the intron or lacked the intron within the mt SSU rRNA gene. Screening by means of Southern hybridization and PCR amplification detected the intron in the mt SSU rRNA genes of S. minor, S. trifoliorum and Sclerotium cepivorum, but not in other members of the Sclerotiniaceae, such as Botrytis anamorphs of Botryotinia spp., or in other ascomycetous and basidiomycetous fungi.

Amino Acid Sequence↗

The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis.

The omptins are a family of enterobacterial surface proteases/adhesins that share high sequence identity and a conserved beta-barrel fold in the outer membrane. The omptins are multifunctional, and the individual omptins exhibit differing virulence-associated functions. The Pla plasminogen activator of Yersinia pestis contributes by several mechanisms to bacterial invasiveness and the systemic, uncontrolled proteolysis in plague. Pla proteolytically activates the human proenzyme plasminogen and inactivates the antiprotease alpha2-antiplasmin, and its binding to laminin localizes the uncontrolled plasmin activity onto basement membranes. These properties enhance bacterial migration through tissue barriers. Pla also degrades circulating complement proteins and functions in bacterial invasion into human epithelial cells. PgtE of Salmonella enterica and OmpT of Escherichia coli have been shown to degrade cationic antimicrobial peptides from epithelial cells or macrophages. PgtE and SopA of Shigella flexneri appear important in the intracellular phases of salmonellosis and shigellosis, whereas functions of OmpT have mainly been associated with protein degradation in E. coli cells. The differing virulence roles and functions have been attributed to minor sequence variations at the surface-exposed regions important for substrate recognition, to the dependence of omptin functions on lipopolysaccharide, and to the different regulation of omptin expression.

Adhesins, Bacterial↗

The shaping of mitochondrial DNA phylogeographic patterns of the brown hare (Lepus europaeus) under the combined influence of Late Pleistocene climatic fluctuations and anthropogenic translocations.

The phylogeographic structure of the brown hare (Lepus europaeus) was studied by analysing mtDNA control region sequences of 98 individuals from continental and insular Greece, Bulgaria, Cyprus and northern Israel, together with 44 published sequences from Italy and central Europe. We found two distinct clades separated by an average nucleotide divergence of 6.6%, which may correspond to a Balkan and to an Asia Minor refugium. The estimated time of separation of the two clades was dated back to 105,000- 490,000 years ago. These two clades coexist in the area of northeastern Greece and Bulgaria, most likely as a result of a post-glacial northward expansion. Within the southern Balkan refugium, network analyses showed geographical structuring, which supports the hypothesis of several isolated Late Pleistocene populations. The central European and Italian populations appear to have originated from a non-detected northern Balkan population that was genetically closely related to some northern Greek populations, as a result of postglacial expansion, translocations or a combination of both. Moreover, several cases of ancient and recent translocations by humans were detected, especially for some island populations, while the eastern Aegean islands off the Asia Minor coast were most likely colonized naturally through Late Pleistocene land bridge connection. The genetic analysis presented here provides a framework for designing proper conservation and management guidelines for this species.

Animals↗

The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors.

The human endogenous retrovirus type W (HERV-W) family includes proviruses with intact protein-coding regions that appear to be under selection pressure, suggesting that some HERV-W proviruses may remain active in higher primates. The envelope glycoprotein (Env) encoded by HERV-W is highly fusogenic, is naturally expressed in human placental syncytiatrophoblasts, and has been reported to function as a superantigen in lymphocyte cultures. Recent evidence suggested that HERV-W Env can mediate syncytium formation by interacting with the human sodium-dependent neutral amino acid transporter type 2 (hASCT2; gene name, SLC1A5) (J.-L. Blond, D. Lavillette, V. Cheynet, O. Bouton, G. Oriol, S. Chapel-Fernandez, B. Mandrand, F. Mallet, and F.-L. Cosset, J. Virol. 74:3321-3329, 2000) and that it can pseudotype human immunodeficiency virus cores (D. S. An, Y. Xie, and I. S. Y. Chen, J. Virol. 75:3488-3489, 2001). By using cell-cell fusion and pseudotype virion infection assays, we found that HERV-W Env efficiently uses both hASCT2 and the related transporter hASCT1 (gene name, SLC1A4) as receptors. In addition, although HERV-W Env mediates only slight syncytium formation or infection of mouse cells, it utilizes the mouse transporters mASCT1 and mASCT2 when their sites for N-linked glycosylation are eliminated by mutagenesis. Consistent with their role as a battlefield in host-virus coevolution, the viral recognition regions in ASCT1 and ASCT2 of humans and mice are highly divergent compared with other regions of these proteins, and their ratios of nonsynonymous to synonymous nucleotide sequence changes are extremely large. The recognition of ASCT1 and ASCT2 despite this divergence of their sequences strongly suggests that the use of both receptors has been highly advantageous for survival and evolution of the HERV-W family of retroviruses.

Amino Acid Sequence↗

Collateralization in the mammalian nervous system.

After reviewing the loci of origin for neurons with collateralized axons, some hypotheses on their distribution in the mammalian nervous system, on their functional contributions and on their significance in the course of encephalization are discussed. In principle, the distribution of collateralized neurons seems to be restricted to anatomical circuits subserving unspecific activation of forebrain regions and controlling body balance and movements. Concerning the limbic system, a minor degree of collateralization seems to exist only in less encephalized species. Based on a number of anatomical and functional arguments, it is assumed that the significance of collateralization fades in the course of encephalization.

Animals↗

Concepts of fever.

If asked to define fever, most physicians would offer a thermal definition, such as "fever is a temperature greater than...." In offering their definition, many would ignore the importance of the anatomic site at which temperature measurements are taken, as well as the diurnal oscillations that characterize body temperature. If queried about the history of clinical thermometry, few physicians could identify the source or explain the pertinacity of the belief that 98.6 degrees F (37.0 degrees C) has special meaning vis-à-vis normal body temperature. Fewer still could cite the origin of the thermometer or trace the evolution of modern concepts of clinical thermometry. Although many would have some knowledge of the fundamentals of thermoregulation and the role played by exogenous and endogenous pyrogens in the induction of fever, few would have more than a superficial knowledge of the broad biological activities of pyrogenic cytokines or know of the existence of an equally complex and important system of endogenous cryogens. A distinct minority would appreciate the obvious paradoxes inherent in an enlarging body of data concerned with the question of fever's adaptive value. The present review considers many of these issues in the light of current data.

Cytokines↗

Natural history of the recombinant (8) syndrome.

The recombinant 8[Rec(8)] syndrome [rec(8), (8qter-->8q22.1::8p23.1-->8qter] is due to a parental inv(8)(8pter-->8p23.1::8q22.1-->8p23.1::8q22+ ++.1-->8qter). All inv(8) parents we have studied were of Hispanic origin. The Rec(8) phenotype consists of a characteristic set of minor facial anomalies, cardiovascular and other major malformations, and moderate to severe mental retardation. The clinical phenotype is relatively consistent in all published cases; however the natural history of the condition has remained unknown. Retrospective and prospective information on 42 propositi, spanning a period from 5 days to 23 years, allowed us to define the natural history of this syndrome, tabulate the frequency and the evolution of phenotypic abnormalities, and share our experience with different therapeutic approaches.

Abnormalities, Multiple↗

Isozyme multiplicity with anomalous dimer patterns in a class III alcohol dehydrogenase. Effects on the activity and quaternary structure of residue exchanges at "nonfunctional" sites in a native protein.

The isozymes of class III alcohol dehydrogenase/glutathione-dependent formaldehyde dehydrogenase from cod were characterized. They exhibited three unexpected properties of general interest. First, these dimeric isozymes, derived from two types of subunit (h and l, for high- and low-activity forms), were recovered from liver preparations in only the homodimeric ll and heterodimeric hl combinations. Dissociation and reassociation of the isolated hl form in vitro also resulted in lower yields of the hh than the ll homodimer, although class III subunits are usually freely associable over wide borders of divergence (human and Drosophila). The h and l primary structures show that both chain types are characteristic of class III enzymes, without large amino acid replacements at positions of known subunit interactions. Hence, the hh dimer partial restriction indicates nontraditional alterations at h-subunit interfaces. The structure provides a possible explanation, in the form of h-chain modifications that may influence the anchoring of a loop at positions of two potentially deamidative beta-aspartyl shifts at distant Asn-Gly structures. Second the ll and hl forms differ in enzymatic properties, having 5-fold different K(m) values for NAD+ at pH 8, different K(m) values for S-(hydroxymethyl)glutathione (10 versus 150 microM), and different specific activities (4.5 versus 41 units/mg), with ll resembling and hl deviating from human and other class III alcohol dehydrogenases. However, functional residues lining substrate and coenzyme pockets in the known conformations of homologous forms are largely identical in the two isozymes [only minor conservative exchanges of Val/Leu116, Val/Leu203, Ile/Val224, and Ile/Val269 (numbering system of the human class I enzyme)], again indicating effects from distantly positioned h-chain replacements. Third, the two isozymes differ a surprising amount in amino acid sequence (18%, the same as the piscine/ human difference), reflecting a remarkably old isozyme duplication or, more probably, discordant accumulation of residue exchanges with greater speed of evolution for one of the subunits (h chain) than is typical for the slowly evolving class III alcohol dehydrogenase.

Aldehyde Oxidoreductases↗

Volumetric face lifting.

The evolution of the face-lift technique used by the author, and the major contribution toward this development from Sydney Coleman's description of lipostructure, are described. At present, the superficial adipocutaneous system (SACS) face lift is almost always associated with a lipostructure performed in the same operative session. In most anatomical locations the structural fat grafting is done before the subfat undermining, although some minor touch-up lipostructure may be done at the end of the face lift.

Adipose Tissue↗

From genes to individuals: developmental genes and the generation of the phenotype.

The success of the genetic approach to developmental biology has provided us with a suite of genes that are involved in the regulation of ontogenetic pathways. It is therefore time to ask whether and how such genes might be involved in the generation of adaptive phenotypes. Unfortunately, the current results do not provide a clear answer. Most of the genes that have been studied by developmental biologists affect early embryonic traits with significant effects on the whole organism. These genes are often highly conserved which allows us to do comparative studies even across phyla. However, whether the same genes are also involved in short-term ecological adaptations remains unclear. The suggestion that early acting ontogenetic genes may also affect late phenotypes comes from the genetic analysis of quantitative traits like bristle numbers in Drosophila. A rough mapping of the major loci affecting these traits shows that these loci might correspond to well known early acting genes. On the other hand, there are also many minor effect loci that are as yet uncharacterized. We suggest that these minor loci might correspond to a different class of genes. In comparative studies of randomly drawn cDNAs from Drosophila we find that there is a large group of genes that evolve fast and that are significantly under-represented in normal genetic screens. We speculate that these genes might provide a large, as yet poorly understood, reservoir of genes that might be involved in the evolution of quantitative traits and short-term adaptations.

Adaptation, Physiological↗

The effect of tirofiban on ST segment resolution in patients with non-ST elevated myocardial infarction.

ST segment resolution in ST elevated myocardial infarction has independent predictive value for congestive heart failure and death at 30 days. ST segment depression in unstable angina pectoris (UAP) and non-ST elevated myocardial infarction (NSTEMI) predicts high risk of MI and death and may discriminate patients likely to have greater benefit from aggressive antithrombotic and interventional therapy. This study assessed the effect of tirofiban added to conventional treatment on ST segment resolution in NSTEMI patients. Sixty-four patients were randomized to one of the two groups: 32 patients received conventional treatment while tirofiban was added in the second group of 32 patients. In the first group, 6 patients refused to participate further after giving initial informed consent while 1 patient in the tirofiban group dropped out. We had 26 patients (mean age, 59 years) in the conventional treatment group and 31 patients (mean age, 59 years) received also tirofiban. Tirofiban was administered by intravenous infusion over a 72 hour period. More than 50% regression of depression was considered to be ST segment resolution. The characteristics of the two groups were comparable (Table I). The ST segment resolution evolution did not differ at the 4th and 24th hours between the two groups. Significant differences occurred in the 72nd hour ECG (Table III). ST resolution was present in 67.9% of the tirofiban patients and in 32.1% of the conventional treatment group (P < 0.05). Tirofiban treatment was not associated with an increase in major bleeding even though there was a trend toward an increase in minor bleeding cases and did not influence the occurrence of refractory angina pectoris.

Electrocardiography↗

Simulating the impact of cross resistance between Bt toxins in transformed clover and apples in New Zealand.

Simulation were conducted to guide development of resistance management strategies aimed at prolonging the usable life of B. thuringiensis (Bt) endotoxins in multiple cropping situations, where different crops expressing Bt endotoxins are host plants for a common pest. We used the New Zealand apple and clover model ecosystem to explore the relative impact on the rate of resistance development of varying levels of cross-resistance between different toxins expressed in these 2 potentially Bt-transformed crops. These 2 crops are hosts for a complex of leaf-rollers in New Zealand, including the light-brown apple moth, used here as the model pest. Cross-resistance was varied between 0.0 and 0.5 (zero to partial cross-resistance) to allow for the case in which selection by one plant has a potential effect on resistance to the toxin in another plant. The largest factor affecting the evolution of resistance was the total habitat area occupied by transgenic orchards. The proportion of the clover habitat that was transformed was also an important factor, even in the absence of cross-resistance. The effect of increasing the proportion of the second transformed crop (clover) acted on resistance evolution mainly by reducing the external refuge of susceptibility for the transgenic orchards. Hence, the ecological implications of reducing the available source of susceptible insects from clover, which can help to slow resistance development in the orchard ecosystem, had a more significant impact than the presence of cross-resistance. Partial cross-resistance between different toxins in the separate crops was overall of relatively minor importance. These simulations have implications for deployment decisions for individual transformed crops in multiple cropping systems, where there is the potential for the crops to serve as refugees for each other. These decisions may need to focus less on cross-resistance between toxins, than on economic trade-offs between the relative roles of individual crops as refugia maintaining susceptibility in the system as a whole.

Animals↗

The pathogenesis of giant cell arteritis: morphological aspects.

The light-microscopic, electron-microscopic and immunocytochemical characteristics of giant cell arteritis (GCA) have been investigated in a number of studies on temporal arteries. Arterial atrophy and calcification of the internal elastic membrane appear to be prerequisites for the evolution of the inflammatory process. Foreign body giant cells form close to calcifications, apparently without connection with other inflammatory cells and probably by the fusion of modified vascular smooth muscle cells. The foreign body giant cells attack the calcifications. Lymphocytes accumulate around them and may be found in pockets in their cell surface. This focal reaction is found in atrophic, calcified arterial segments in a minority of inflamed temporal artery biopsies. More commonly seen is a diffuse mononuclear attack of the vessel wall in atrophic as well as non-atrophic segments which leads to severe arterial dilatation. Langhans giant cells form by the fusion of macrophages in the diffuse inflammatory infiltrate. The fact that the diffusely inflamed arteries are markedly widened compared to the focally inflamed vessels suggests that the inflammatory process starts as a focal foreign body giant cell reaction directed at calcifications which in turn initiates a more diffuse and widespread inflammation.

Aorta↗

Evolution of human Polyomavirus JC: implications for the population history of humans.

The polyomavirus JC virus (JCV), the etiological agent of progressive multifocal leukoencephalopathy, is ubiquitous in the human population, infecting children asymptomatically, then persisting in the kidney. The main mode of transmission of JCV is from parents to children through long-term cohabitation. Twelve JCV subtypes that occupy unique domains in Europe, Africa, and Asia have been identified. Here, we attempted to elucidate the evolutionary relationships among JCV strains worldwide using the whole-genome approach with which a highly reliable phylogeny of JCV strains can be reconstructed. Sixty-five complete JCV DNA sequences, derived from various geographical regions and belonging to 11 of the 12 known subtypes, were subjected to phylogenetic analysis using three independent methods: the neighbor-joining, maximum parsimony, and maximum likelihood methods. The trees obtained with these methods consistently indicated that ancestral JCVs were divided into three superclusters, designated as Types A, B, and C. A split in Type A generated two subtypes, EU-a and -b, mainly containing European and Mediterranean strains. The first split in Type B generated Af2 (the major African subtype). Subsequent splits in Type B generated B1-c (a minor European subtype) and all seven Asian subtypes (B1-a, -b, -d, B2, MY, CY, and SC). Type C generated a single subtype (Af1), consisting of strains derived from western Africa. While the present findings provided a basis on which to classify JCV into types or subtypes, they have several implications for the divergence and migration of human populations.

Base Sequence↗

Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution.

Neuronal apoptosis inhibitory protein (NAIP, also known as BIRC1) is a member of the conserved inhibitor of apoptosis protein (IAP) family. Lineage-specific rearrangements and expansions of this locus have yielded different copy numbers among primates and rodents, with human retaining a single functional copy and mouse possessing several copies, depending on the strain. Roles for this gene in disease have been documented, but little is known about transcriptional regulation of NAIP. We show here that NAIP has multiple promoters sharing no similarity between human and rodents. Moreover, we demonstrate that multiple, domesticated long terminal repeats (LTRs) of endogenous retroviral elements provide NAIP promoter function in human, mouse, and rat. In human, an LTR serves as a tissue-specific promoter, active primarily in testis. However, in rodents, our evidence indicates that an ancestral LTR common to all rodent genes is the major, constitutive promoter for these genes, and that a second LTR found in two of the mouse genes is a minor promoter. Thus, independently acquired LTRs have assumed regulatory roles for orthologous genes, a remarkable evolutionary scenario. We also demonstrate that 5' flanking regions of IAP family genes as a group, in both human and mouse are enriched for LTR insertions compared to average genes. We propose several potential explanations for these findings, including a hypothesis that recruitment of LTRs near NAIP or other IAP genes may represent a host-cell adaptation to modulate apoptotic responses.

5' Flanking Region↗

Evolution of metal pollution in the golden horn (Turkey) sediments between 1912 and 1987.

The Golden Horn is a heavily polluted water body in a large metropolitan area with a population of approximately 10 million. A 3-m long undisturbed core sample was collected in the Golden Horn, from research vessel RV Knorr, during the third leg of the joint Turkish--American Black Sea expedition in 1989. The core was sliced and dated using the 210Pb isotope technique. The bottom of the core corresponds to the year 1912. Each slice was analysed for major, minor and trace elements by inductively coupled plasma emission spectrometry (ICP). The masses of the measured elements can account for approximately half of the sediment mass. The lithophilic elements Li, K, Rb, Mg, Ca, Ba, Al, La, Ti, V, Mn, Fe, Co and Ni account for more than 90% of the elemental mass and do not show any change in their concentrations between 1912 and 1987. Although anthropogenic elements Mo, Zn, Cr, Cu, Ag, and Cd account for a minute fraction of the elemental mass, their concentrations increase along the core, signifying human influence on chemical composition of the Golden Horn Sediments. Lead was enriched at the bottom of the core suggesting pollution of Golden Horn sediments by this element even at the beginning of the century, but observed concentrations of the remaining anthropogenic elements, at the bottom of the core, can be explained by sedimentary material. Concentrations of pollution-derived elements do not change significantly between 1912 and 1950, but their concentrations increase sharply in the second half of the century. A factor analysis applied to the data set has shown that the inorganic fraction of the Golden Horn sediments includes crustal, marine and two anthropogenic components. One of the anthropogenic components is attributed to the discharges from an iron and steel plant. The second anthropogenic component, which accounted for a larger fraction of system variance, is due to discharges from industries, particularly metalwork plants.

Anthropology↗

Physical localization of the 18S-5.8S-26S rDNA and sequence analysis of ITS regions in Thinopyrum ponticum (Poaceae: Triticeae): implications for concerted evolution.

Fluorescence in situ hybridization was used in Thinopyrum ponticum, a decaploid species, and its related diploid species, to investigate the distribution of the 18S-5.8S-26S rDNA. The distribution of rDNA was similar in all three diploid species (Th. bessarabicum, Th. elongatum and Pseudoroegneria stipifolia). Two pairs of loci were observed in each somatic cell at metaphase and interphase. One pair was located near the terminal end and the other in the interstitial regions of the short arms of one pair of chromosomes. However, all of the major loci in Th. ponticum were located on the terminal end of the short arms of chromosomes, and one chromosome had only one major locus. The maximum number of major loci detected on metaphase spreads was 20, which was the sum of that of its progenitors. The interstitial loci that exist in the possible diploid genome donor species were probably 'lost' during the evolutionary process of the decaploid species. A number of minor loci were also detected on whole regions of two pairs of homologous chromosomes. These results suggested that the position of rDNA loci in the Triticeae might be changeable rather than fixed. Positional changes of 18S-5.8S-26S rDNA loci between Th. ponticum and its candidate genome donors indicate that it is almost impossible to find a genome in the polyploid species that is completely identical to that of its diploid donors. The possible evolutionary significance of the distribution of the rDNA is also discussed. Internal transcribed spacer (ITS) regions of nuclear DNA in Th. ponticum were investigated by PCR amplification and sequencing. The sequence data from five positive clones selected at random, together with restriction site analysis, indicated that the ITS repeated units are nearly homogeneous in this autoallodecapolypoid species. Combined with in situ hybridization results, the data led to the conclusion that the ITS region has experienced interlocus as well as intralocus concerted evolution. Phylogenetic analyses showed that the sequences from Th. ponticum have concerted to the E genome repeat type.

DNA, Ribosomal Spacer↗

A highly conserved sequence in H1 histone genes as an oligonucleotide hybridization probe: isolation and sequence of a duck H1 gene.

A 3.5-kb HindIII fragment of a histone gene cluster was isolated from a recombinant phage out of a duck genomic library. This DNA contains a duck H1 gene and its flanking sequences. The hybridization probe, which was used to screen for the H1 gene, had been designed on the basis of a comparative analysis of available H1 gene and protein data. Most H1 histones contain repeated motifs in their C-terminal domain, and these form part of an octapeptide (ser pro lys lys ala lys lys pro) that is highly conserved in many H1 histone proteins. A comparison of the duck H1 described here with two different published chicken H1 histone sequences reveals conservative amino acid exchanges at 22 (of 217 and 218, respectively) positions. The homology is maintained at the flanking sequences, and includes the putative H1 histone gene-specific signal structures and the established 3' stem and loop structures and the CAAGA box. The duck H1 gene and its flanking sequence have been found in identical arrangements in two recombinant bacteriophages, but minor sequence variations and genomic Southern blotting after HindIII digestion suggest that we have either isolated alleles of this genome segment or that the gene described may occur twice per haploid duck genome.

Amino Acid Sequence↗