Showing papers by "University of Leicester published in 1991"

Social Network Analysis: A Handbook

Abstract: Networks and Relations The Development of Social Network Analysis Handling Relational Data Lines, Direction and Density Centrality and Centralization Components, Cores, and Cliques Positions, Roles, and Clusters Dimensions and Displays Appendix Social Network Packages

Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts.

Abstract: FERRITINis important in iron homeostasis. Its twenty-four chains of two types, H and L, assemble as a hollow shell providing an iron-storage cavity1–3. Ferritin molecules in cells containing high levels of iron tend to be rich in L chains, and may have a long-term storage function, whereas H-rich ferritins are more active in iron metabolism3–7. The molecular basis for the greater activity of H-rich ferritins has until now been obscure, largely because the structure of H-chain ferritin has remained unknown owing to the difficulties in obtaining crystals ordered enough for X-ray crys-tallographic analysis. Here we report the three-dimensional structure of a human ferritin H-chain homopolymer. By genetically engineering a change in the sequence of the intermolecular contact region, we obtained crystals isomorphous with the homologous rat L ferritin8–9 and of high enough quality for X-ray diffraction analysis. The X-ray structure of human H ferritin shows a novel metal site embedded within each of its four-helix bundles and we suggest that ferroxidase activity associated with this site accounts for its rapid uptake of iron10.

DNA Gyrase: Structure and Function

Abstract: DNA gyrase is an essential bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DNA. Gyrase belongs to a class of enzymes known as topoisomerases that are involved in the control of topological transitions of DNA. The mechanism by which gyrase is able to influence the topological state of DNA molecules is of inherent interest from an enzymological standpoint. In addition, much attention has been focused on DNA gyrase as the intracellular target of a number of antibacterial agents as a paradigm for other DNA topoisomerases. In this review we summarize the current knowledge concerning DNA gyrase by addressing a wide range of aspects of the study of this enzyme.

The IUGS systematics of igneous rocks

Abstract: In order to create a sustainable classification of igneous rocks which all geologists might use, an international body was set up by the IUGS: the IUGS Subcommission on the Systematics of Igneous Rocks In the course of creating the classification, the Subcommission has established ten principles for its construction and for defining an appropriate nomenclature The principles are: (1) use descriptive attributes; (2) use actual properties; (3) ensure suitability for all geologists; (4) use current terminology; (5) define boundaries of rock species; (6) keep it simple to apply; (7) follow natural relations; (8) use modal mineralogy; (9) if mode not feasible, use chemistry; (10) follow terminology of other IUGS advisory bodies These principles and their rationale have not previously been enunciated The classification separates and individually classifies the pyroclastic, carbonatitic, melititic, lamprophyric and charnockitic rocks before entering the main QAPF classification for plutonic and volcanic rocks which is based on the modal mineral proportions of quartz (Q), alkali feldspar (A) and plagioclase (P) or of alkali feldspar (A), plagioclase (P) and feldspathoids (F) Rocks with mafic content >90% have their own classification If the mineral mode cannot be determined as is often the case for volcanic rocks, then a chemical classification of total alkalis versus silica (TAS) is used The nomenclature for these classifications necessitates only 297 rock names out of the c 1500 that exist

Designing Experiments and Analysing Data

Abstract: Designing Experiments and Analysing Data. By S. E. Maxwell and H. D. Delaney. ISBN 0 534 10374 X. Wadsworth, Belmont, 1990. xvi + 902 pp. £19.95 (paperbound).

Minisatellite repeat coding as a digital approach to DNA typing

Abstract: Most DNA typing systems used in forensic and legal medicine assay allelic length variation at tandem repetitive DNA regions such as minisatellites. A simple alternative approach that displays patterns of variant repeat units along minisatellite alleles is described here. This produces DNA profiles as extraordinarily variable digital sequences appropriate for forensic investigations, including computer databasing, and for analysing allele diversity and the role of recombination in minisatellite instability.

Identification of the skeletal remains of a murder victim by DNA analysis

Abstract: THERE is considerable anthropological and forensic interest in the possibility of DNA typing skeletal remains. Trace amounts of DNA can be recovered even from 5,500-year-old bones and multicopy human mitochondrial DNA sequences can frequently be amplified from such DNA using the polymerase chain reaction (PCR)1,2. But given the sensitivity of PCR, it is very difficult to exclude contaminating material. We now report the successful identification of the 8-year-old skeletal remains of a murder victim, by comparative typing of nuclear microsatellite markers3–5 in the remains and in the presumptive parents of the victim. This analysis establishes the authenticity of the bone DNA and the feasibility of bone DNA typing in forensic investigations.

Uniparental paternal disomy in Angelman's syndrome

Abstract: Angelman's syndrome and Prader-Willi syndrome are both causes of mental retardation with recognisable, but quite different, clinical phenotypes. Both are associated with deletions of chromosome 15q11-13, of maternal origin in Angelman's and paternal in Prader-Willi. Prader-Willi can arise by inheritance of two chromosomes 15 from the mother and none from the father (uniparental maternal disomy). In 2 patients with Angelman's syndrome we found evidence of uniparental paternal disomy. The phenotypic effects of maternal and paternal disomy of chromosome 15 are very different and inheritance of two normal 15s from one parent does not lead to normal development—strong evidence in man for genomic imprinting, in which the same gene has different effects dependent upon its parental origin.

A Monte Carlo method for Bayesian inference in frailty models.

Abstract: Many analyses in epidemiological and prognostic studies and in studies of event history data require methods that allow for unobserved covariates or "frailties." Clayton and Cuzick (1985, Journal of the Royal Statistical Society, Series A 148, 82-117) proposed a generalization of the proportional hazards model that implemented such random effects, but the proof of the asymptotic properties of the method remains elusive, and practical experience suggests that the likelihoods may be markedly nonquadratic. This paper sets out a Bayesian representation of the model in the spirit of Kalbfleisch (1978, Journal of the Royal Statistical Society, Series B 40, 214-221) and discusses inference using Monte Carlo methods.

Late Cenozoic crustal extension and basin formation in west Turkey

Abstract: It is proposed that north–south crustal extension and related sedimentary basin formation commenced in the early Miocene. This extension is believed to be related to a spreading of a thickened crust as a result of Palaeogene compression. That such spreading commenced virtually immediately after the cessation of this compression is considered to be due to the high thermal profile of the crust in that area at the end of the Palaeogene.

Rapid formation of Ontong Java Plateau by Aptian mantle plume volcanism

Abstract: The timing of flood basalt volcanism associated with formation of the Ontong Java Plateau (OJP) is estimated from paleomagnetic and paleontologic data. Much of OJP formed rapidly in less than 3 million years during the early Aptian, at the beginning of the Cretaceous Normal Polarity Superchron. Crustal emplacement rates are inferred to have been several times those of the Deccan Traps. These estimates are consistent with an origin of the OJP by impingement at the base of the oceanic lithosphere by the head of a large mantle plume. Formation of the OJP may have led to a rise in sea level that induced global oceanic anoxia. Carbon dioxide emissions likely contributed to the mid-Cretaceous greenhouse climate but did not provoke major biologic extinctions.

EXOSAT observations of clusters of galaxies – I. The X-ray data

Abstract: X-ray observations of 45 clusters of galaxies made with the European X-ray Observatory Satellite, EXOSAT, are presented The 01−20 keV spectra obtained constitute the largest homogeneous spectral sample presently available Here the analysis of the spectral and imaging data is described A significant scatter in the correlation between the X-ray luminosity and temperature, which can be interpreted as variations in the ratio of the gas mass to total mass amongst the clusters, is found The measured iron abundances are consistent with a canonical average value of 03 solar

Fluid influence on the trace element compositions of subduction zone magmas

Abstract: Subduction zones represent major sites of chemical fractionation within the Earth. Element pairs which behave coherently during normal mantle melting may become strongly decoupled from one another during the slab dehydration processes and during hydrous melting conditions in the slab and in the mantle wedge. This results in the large ion lithophile elements (e.g. K, Rb, Th, U, Ba) and the light rare earth elements being transferred from the slab to the mantle wedge, and being concentrated within the mantle wedge by hydrous fluids, stabilized in hydrous phases such as hornblende and phlogopite, from where they are eventually extracted as magmas and contribute to growth of the continental crust. High-field strength elements (e.g. Nb, Ta, Ti, P, Zr) are insoluble in hydrous fluids and relatively insoluble in hydrous melts, and remain in the subducted slab and the adjacent parts of the mantle which are dragged down and contribute to the source for ocean island basalts. The required element fractionations result from interaction between specific mineral phases (hornblende, phlogopite, rutile, sphene, etc.) and hydrous fluids. In present day subduction magmatism the mantle wedge contributes dominantly to the chemical budget, and there is a requirement for significant convection to maintain the element flux. In the Precambrian, melting of subducted ocean crust may have been easier, providing an enhanced slab contribution to continental growth.

Asteroseismology of the DOV star PG 1159 - 035 with the Whole Earth Telescope

Abstract: Results are reported from 264.1 hr of nearly continuous time-series photometry on the pulsating prewhite dwarf star (DPV) PG 1159 - 035. The power spectrum of the data set is completely resolved into 125 individual frequencies; 101 of them are identified with specific quantized pulsation modes, and the rest are completely consistent with such modal assignment. It is argued that the luminosity variations are certainly the result of g-mode pulsations. Although the amplitudes of some of the peaks exhibit significant variations on the time scales of a year or so, the underlying frequency structure of the pulsations is stable over much longer intervals. The existing linear theory is invoked to determine, or strongly constrain, many of the fundamental physical parameters describing this star. Its mass is found to be 0.586 solar mass, is rotation period 1.38 days, its magnetic field less than 6000 G, its pulsation and rotation axes to be aligned, and its outer layers to be compositionally stratified.

Superhumps, resonances and accretion discs

Abstract: The structure of accretion discs within binary systems is shown to be influenced by the excitation of resonances within the disc. Of particular importance is that near the 3:1 commensurability with the stars' orbit. This can be used to explain the superhump phenomenon of SU UMa dwarf novae in superoutburst. This resonance can only appear for mass ratios which satisfy M 1 /M 2 ≤ 0.25-0.33, for larger mass ratios the available resonances are weaker and of the wrong form to produce the superhump phenomenon. The mass-transfer stream is shown to be an important contributor to growth rate of the resonance.

Loss of chromosome 17p13 sequences and mutation of p53 in human breast carcinomas.

Abstract: DNAs from ninety seven primary breast carcinoma biopsies have been examined for loss of sequences on 17p13. In addition, immunohistochemical analysis has been carried out on the majority of these cases to determine whether p53 gene expression can be detected. Detection of p53 expression is taken to indicate mutation of p53 leading to stabilisation of the protein and thus detectable levels of p53 in the cell. In 86% of breast carcinoma samples where both allele loss and expression data were available, loss of sequences on 17p13 and/or expression of p53 was detected. Alterations to p53, whether loss of one allele or mutation, are therefore by far the most common changes so far detected in primary human breast tumours. In three cases where expression of p53 could be detected by immunohistochemistry, the precise mutation to p53 was identified. All three mutations fall within the regions which are highly conserved in p53, encoded by exons 5 to 8. Two are single base changes leading to misense mutations, and the third is a single base-pair deletion. The expression of the latter gene would result in production of a truncated protein which should lack normal biological activities.

Complement activation and antibody binding by pneumolysin via a region of the toxin homologous to a human acute-phase protein

Abstract: Summary Pneumolysin, a membrane-damaging toxin, is known to activate the classical complement pathway. We have shown that 1 μg ml−1 of pneumolysin can activate complement, which is a much lower level than observed previously. We have identified two distinct regions of pneumolysin which show homology with a contiguous sequence within acute-phase proteins, including human C-reactive protein (CRP). Site-directed mutagenesis of the pneumolysin gene was used to change residues common to pneumolysin and CRP. Some of the modified toxins had a reduced ability both to activate complement and bind antibody. We suggest that the ability of pneumolysin to activate complement is related to its ability to bind the Fc portion of immunoglobulin G.

Molecular transfer of a species-specific behavior from Drosophila simulans to Drosophila melanogaster.

Abstract: Drosophila males modulate the interpulse intervals produced during their courtship songs. These song cycles, which are altered by mutations in the clock gene period, exhibit a species-specific variation that facilitates mating. We have used chimeric period gene constructs from Drosophila melanogaster and Drosophila simulans in germline transformation experiments to map the genetic control of their song rhythm difference to a small segment of the amino acid encoding information within this gene.

EXOSAT observations of clusters of galaxies – II. X-ray to optical correlations

Abstract: The results obtained for clusters of galaxies using X-ray data from the European X-ray Observatory Satellite, EXOSAT, are compared with the optical, infrared and radio properties of the clusters taken from the literature. A number of strong correlations are found. The ratios of the intracluster medium (ICM) temperature and the cluster velocity dispersion, β, have a mean of less than one, in agreement with values obtained from the surface brightness distribution of the X-ray emission, thus resolving the Beta problem

Prevalence of liver disease in cystic fibrosis

Abstract: To assess the prevalence, demography, and clinical features of liver disease among patients with cystic fibrosis the case notes of 524 patients of all ages who were attending the cystic fibrosis clinic were studied. Computer databases were used to establish the condition of the liver in a further 576 such patients. The overall prevalence of overt liver disease indicated by the presence of an enlarged liver or spleen (or both) was 4.2%. The age related prevalence rose to a peak in adolescence, and then fell in patients over 20 years old. The implied increase in mortality among those with liver disease was not explained by deaths from liver disease, which were rare. Male patients were significantly more affected than female, the ratio being 3:1 among adolescents. Increasing prevalence of liver disease in patients with cystic fibrosis is, therefore, not just a result of longevity.

Are oceanic plateaus sites of komatiite formation

Abstract: During Cretaceous and Tertiary time a series of oceanic terranes were accreted onto the Pacific continental margin of Colombia The island of Gorgona is thought to represent part of the most recent, early Eocene, terrane-forming event Gorgona is remarkable for the occurrence of komatiites of middle Cretaceous age, having MgO contents up to 24% The geochemistry of spatially and temporally associated tholeiites suggests that Gorgona is an obducted fragment of the oceanic Caribbean Plateau, postulated by Duncan and Hargraves (1984) to have formed at 100 to 75 Ma over the Galapagos hotspot Further examples of high-MgO oceanic lavas that may represent fragments of the Caribbean Plateau occur in allochthonous terranes on the island of Curacao in the Netherlands Antilles and in the Romeral zone ophiolites in the southwestern Colombian Andes These and other examples suggest that the formation of high-MgO liquids may be a feature of oceanic-plateau settings The association of Phanerozoic komatiites with oceanic plateaus, coupled with thermal considerations, provides a plausible analogue for the origin of some komatiite-tholeiite sequences in Archean greenstone belts

Block of calcium-activated potassium channels in mammalian arterial myocytes by tetraethylammonium ions

Abstract: The effects of tetraethylammonium ions (TEA+) and tetrapentylammonium ions (TPeA+) on Ca2(+) -activated K+ (KCa) channels were studied in membrane patches from mesenteric arterial myocytes. External TEA+ produced a flickery block. The concentration dependence for reduction in mean unitary current was consistent with 1:1 binding, with dissociation constants (Kd) in rat and rabbit of 196 and 159 microM at 0 mV, and the block was weakly voltage dependent. Rate constants for blocking and unblocking were 380 mM-1.ms-1 and 73 ms-1, respectively. In patches containing several channels TEA+ reduced average current to the same extent as mean unitary current, implying that TEA+ block is independent of the channel state. Block was unaffected by raising external K+ to 120 mM. External TPeA+ blocked with slower kinetics and lower affinity than TEA+ (Kd, 1.49 mM). The sulfonylurea glibenclamide (10-100 microM), the hyperpolarizing vasodilator cromakalim (5 microM), and internal ATP (1 mM) were without effect on channel activity. We conclude that TEA+ is a relatively effective blocker of single KCa channels of arterial smooth muscle and should block macroscopic currents equally well, whereas external TPeA+ is about eight times less effective.

Restricted gene flow in a moving hybrid zone of the newts triturus cristatus and t. marmoratus in western france.

Abstract: Two hybridizing species of newts, Triturus cristatus and T. marmoratus, with overlapping distributions show a parapatric distribution when surveyed in detail. The factors that govern the distribution of cristatus vs. marmoratus in the departement (province) of Mayenne in western France are identified as forestation and relief. The parapatric hybrid zone running through Mayenne is narrow but widens to approximately 20 km in an area with mixed habitat. In this area most breeding sites are shared and F1 hybrids form about 4% of the total population. Analysis of survey data collected about 30 years previously also shows an essentially parapatric distribution. Comparison of past and present distribution maps reveals that cristatus has superseded marmoratus over large areas in the south of Mayenne. An area where marmoratus replaced cristatus also exists, but it is more limited in size. Gene flow between cristatus and marmoratus is analyzed using 10 diagnostic genetic markers [9 protein loci and mitochondrial (mt) DNA]. In syntopic populations nuclear gene flow is bidirectional with a mean frequency of introgressed alleles (f) of 0.3%. In allotopic populations of cristatus and marmoratus gene flow is present in areas of species replacement (f = 0.3%), while gene flow appears to be absent in those areas that have been continuously occupied by a single species. At the biogeographic level, the presence or absence of introgression is paralleled by the persistence or absence, respectively, of pockets of cristatus-marmoratus syntopy. All F1 hybrids possess the cristatus type mtDNA. This may be due to asymmetric interspecific mate choice and would explain the observed absence of introgression of the maternally inherited mtDNA genome in areas where cristatus replaced marmoratus. The cristatus-marmoratus hybrid zone bears characteristics of both the clinal (parapatric) hybrid zone model and the mosaic hybrid zone model. Such a mixed model-for which we propose the term "reticulate hybrid zone"-can be appreciated only if studied over a two-dimensional geographic area and also through time.

The efficiency of multilocus DNA fingerprint probes for individualization and establishment of family relationships, determined from extensive casework.

Abstract: The properties of human DNA fingerprints detected by multilocus minisatellite probes 33.6 and 33.15 have been investigated in 36 large sibships and in 1,702 Caucasian paternity cases involving the analysis of over 180,000 DNA fingerprint bands. The degree of overlap of minisatellite loci detected by these two probes is shown to be negligible (approximately 1%), and the resulting DNA fingerprints are therefore derived from independent sets of hypervariable loci. The level of allelism and linkage between different hypervariable DNA fragments scored with these probes is also low, implying substantial statistical independence of DNA fragments. Variation between the DNA fingerprints of different individuals indicates that the probability of chance identity is very low (much less than 10(-7) per probe). Empirical observations and theoretical considerations both indicate that genetic heterogeneity between subpopulations is unlikely to affect substantially the statistical evaluation of DNA fingerprints, at least among Caucasians. In paternity analysis, the proportion of nonmaternal DNA fragments in a child which cannot be attributed to the alleged father is shown to be an efficient statistic for distinguishing fathers from nonfathers, even in the presence of minisatellite mutation. Band-sharing estimates between a claimed parent and a child can also distinguish paternity from nonpaternity, though with less efficiency than comparison of a trio of mother, child, and alleged father.

Assessment of quality of life.

Abstract: Assessment of quality of life has emerged in recent years as an important part of the overall evaluation of drug therapy and health care in general. Measurement techniques for this difficult assessment range from simple unqualified questions on patient well-being to complex statistical analyses of a wide range of lifestyle and activity variables. The factors that influence quality of life during chronic drug therapy differ in the treatment of symptomatic (e.g., heart failure) vs asymptomatic (e.g., hypertension) disease, and include drug side effects, relief of symptoms, improved prognosis, return to work, physical activity and the need for further hospital treatments. The manifestation of quality of life varies for different people leading to lack of agreement on the precise definition. The absence of standardization of methods of measurement also contributes to this and leads to lack of comparability of studies and unreasonable claims by some drug manufacturers. Further complicating issues in multicenter trials across countries include language problems and interethnic differences in “sickness” behavior. The recently introduced quality-adjusted life year (QALY) index, designed to take account of both the quality and duration of life in assessing the outcome of treatments, may avoid some of these problems. By classifying illness states (the Rosser index) on the basis of disability and distress, and comparing outcomes in terms of improved prognosis, QALYs have already been used for cost/benefit analyses of a number of new and expensive therapies. Like other methods, QALYs have problems related to variability in individual appreciation of life values. To date, a perfect method of quality of life assessment remains elusive.

Elevation of intracellular free calcium levels in HEp-2 cells infected with enteropathogenic Escherichia coli.

Abstract: Enteropathogenic Escherichia coli (EPEC) are a class of diarrheagenic organisms that induce a characteristic attaching and effacing lesion in enterocytes and various cultured cell lines. Infection of cultured HEp-2 cells by EPEC isolates 2036-80 (serotype O119) and E2348-69 (serotype O127) resulted in significant elevation of intracellular free calcium levels, determined quantitatively with the fluorescent calcium indicator dye 2-([2-bis(carboxymethyl)amino-5-methylphenoxy]methyl)-6-methoxy-8- bis(carboxymethyl)aminoquinoline. This effect, which was not observed on infection with non-lesion-forming E. coli strains, was inhibited by dantrolene, a drug that prevents calcium mobilization from intracellular stores. Moreover, activated protein kinase C in infected cells was dissociated from cell membranes by a process that was inhibited by cyclosporin A, suggesting involvement of the calcium-dependent protease calpain. A qualitative method for observing intracellular calcium fluxes by fluorescence microscopy with the recently described fluorescein-based indicator fluo-3 was used to screen a collection of well-characterized E. coli isolates from patients with infantile enteritis. Increased localized calcium-dependent fluo-3 fluorescence was observed only in HEp-2 cells infected with known lesion-forming EPEC strains. We propose that enhancement of intracellular free calcium levels in enterocytes infected with EPEC would result in formation of the characteristic lesion by calcium-dependent activation of actin-depolymerizing proteins, with eventual loss of absorptive capacity.