Showing papers by "University of Leicester published in 1985"

Hypervariable 'minisatellite' regions in human DNA.

Abstract: The human genome contains many dispersed tandem-repetitive 'minisatellite' regions detected via a shared 10-15-base pair 'core' sequence similar to the generalized recombination signal (chi) of Escherichia coli. Many minisatellites are highly polymorphic due to allelic variation in repeat copy number in the minisatellite. A probe based on a tandem-repeat of the core sequence can detect many highly variable loci simultaneously and can provide an individual-specific DNA 'fingerprint' of general use in human genetic analysis.

Accretion power in astrophysics

Abstract: 1. Accretion as a source of energy 2. Gas dynamics 3. Plasma concepts 4. Accretion in binary systems 5. Accretion discs 6. Accretion on to a compact object 7. Active galactic nuclei 8. Accretion discs in active galactic nuclei 9. Accretion power in active galactic nuclei 10. Thick discs 11. Accretion flows.

Individual-specific 'fingerprints' of human DNA.

Abstract: Simple tandem-repetitive regions of DNA (or 'minisatellites') which are dispersed in the human genome frequently show substantial length polymorphism arising from unequal exchanges which alter the number of short tandem repeats in a minisatellite. We have shown previously that the repeat elements in a subset of human minisatellites share a common 10-15-base-pair (bp) 'core' sequence which might act as a recombination signal in the generation of these hypervariable regions. A hybridization probe consisting of the core repeated in tandem can detect many highly polymorphic minisatellites simultaneously to provide a set of genetic markers of general use in human linkage analysis. We now show that other variant (core)n probes can detect additional sets of hypervariable minisatellites to produce somatically stable DNA 'fingerprints' which are completely specific to an individual (or to his or her identical twin) and can be applied directly to problems of human identification, including parenthood testing.

Forensic application of DNA 'fingerprints'.

Abstract: Many highly polymorphic minisatellite loci can be detected simultaneously in the human genome by hybridization to probes consisting of tandem repeats of the 'core' sequence. The resulting DNA fingerprints produced by Southern blot hybridization are comprised of multiple hypervariable DNA fragments, show somatic and germline stability and are completely specific to an individual. We now show that this technique can be used for forensic purposes; DNA of high relative molecular mass (Mr) can be isolated from 4-yr-old bloodstains and semen stains made on cotton cloth and digested to produce DNA fingerprints suitable for individual identification. Further, sperm nuclei can be separated from vaginal cellular debris, obtained from semen-contaminated vaginal swabs, enabling positive identification of the male donor/suspect. It is envisaged that DNA fingerprinting will revolutionize forensic biology particularly with regard to the identification of rape suspects.

Positive identification of an immigration test-case using human DNA fingerprints

Abstract: The human genome contains a set of minisatellites, each of which consists of tandem repeats of a DNA segment containing the 'core' sequence, a putative recombination signal in human DNA. Multiallelic variation in the number of tandem repeats occurs at many of these minisatellite loci. Hybridization probes consisting of tandem repeats of the core sequence detect many hypervariable minisatellites simultaneously in human DNA, to produce a DNA fingerprint that is completely individual-specific and shows somatic and germline stability. These DNA fingerprints are derived from a large number of highly informative dispersed autosomal loci and are suitable for linkage analysis in man, and for individual identification in, for example, forensic science and paternity testing. They can also be used to resolve immigration disputes arising from lack of proof of family relationships. To illustrate the potential for positive or inclusive identification, we now describe the DNA fingerprint analysis of an immigration case, the resolution of which would have been very difficult and laborious using currently available single-locus genetic markers.

Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome

Abstract: Most of the small number of cases of poliomyelitis which occur in countries where Sabin's attenuated poliovirus vaccines are used are temporally associated with administration of vaccine and involve polioviruses of types 2 and 3 (ref. 1). Recent studies have provided convincing evidence that the Sabin type 2 and 3 viruses themselves may revert to a neurovirulent phenotype on passage in man2–6. We report here that a point mutation in the 5′ noncoding region of the genome of the poliovirus type 3 vaccine consistently reverts to wild type in strains isolated from cases of vaccine-associated poliomyelitis. Virus with this change is rapidly selected on passage through the human gastrointestinal tract. The change is associated with a demonstrable increase in the neurovirulence of the virus.

Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane.

Abstract: It has been known for some years that skeletal muscle develops a high potassium permeability in conditions that produce rigor, where ATP concentrations are low and intracellular Ca2+ is high. It has seemed natural to attribute this high permeability to K channels that are opened by internal Ca2+, especially as the presence of such channels has been demonstrated in myotubes and in the transverse tubular membrane system of adult skeletal muscle. However, as we show here, the surface membrane of frog muscle contains potassium channels that open at low internal concentrations of ATP (less than 2 mM). ATP induces closing of these channels without being split, apparently holding the channels in one of a number of closed states. The channels have at least two open states whose dwell times are voltage-dependent. Surprisingly, we find that these may be the most common K channels of the surface membrane of skeletal muscle.

Multivariate Generalizations of the Proportional Hazards Model

Abstract: A new approach to the analysis of bivariate survival data is presented. It involves the development of "a model for bivariate life-tables...with a single association parameter which is unaffected by monotone transformation of the marginal distributions. Methods for testing and estimating this parameter from right-censored sample pairs using only rank-order information are presented. The model is a generalization of the proportional hazards model and includes a random effect representing heterogeneity of frailty or proneness to failure." A discussion on "the analysis of litter-matched and matched-pair failure-time data is [included]. Some uses of the methods in rank regression problems involving only one right-censored dependent variable are described and a test is proposed for proportional hazards against alternative error structures leading to converging hazards. Finally the methods are compared and validated by Monte-Carlo simulations." Comments by several people and a discussion concerning the paper are included (pp. 108-17). (EXCERPT)

Morphogenesis in Candida Albicans

Abstract: This review will survey environmental controls on the morphology of Candida albicans, describe the cellular and ultrastructural events associated with morphological transitions in this fungus, and attempt to relate biochemical phenomena that have been reported to be associated with dimorphic change to C albicans cell biology The synthesis of the cell wall of C albicans and its control remain largely undiscovered, but it is clear that the cell wall is the principal component involved in shape determination Possible models for C albicans dimorphism will be critically reviewed

Substance P raises neuronal membrane excitability by reducing inward rectification

Abstract: Much interest has recently centred on the properties of peptides that modulate the excitability of nerve cells. Such compounds include the undecapeptide substance P, which is particularly well established as an excitatory neurotransmitter, and we examine here its effects on magnocellular cholinergic neurones taken from the medial and ventral aspects of the globus pallidus of newborn rats and grown in dissociated culture. These neurones have previously been shown to respond to substance P3 and are analogous to the nucleus basalis of Meynert in man, which gives a diffuse projection to the cerebral cortex and whose degeneration is the likely cause of Alzheimer's disease. Substance P depolarizes these cultured neurones by reducing an inwardly rectifying potassium conductances; this conductance has been found in several neuronal types and has similar properties to those of certain other cells. As discussed below, modulation of inward (or anomalous) rectification by substance P implies a self-reinforcing element to the depolarization caused by the peptide.

Geochemistry of Holocene volcanic rocks associated with ridge subduction in Baja California, Mexico

Abstract: Although the geochemistry of magmatism associated with the subduction of oceanic lithosphere is well understood1–6, the geochemical signature of lavas produced shortly after subduction of an oceanic spreading centre has not been characterized. The Baja California peninsula in Mexico provides an ideal scenario to study the latter process. Geophysical models indicate that, in response to oblique collision of the ancestral East Pacific Rise (EPR) with the western seaboard of North America at ∼29 Myr, subduction of the Farallon plate was succeeded by the progressive southwards development of a transform fault system7–9. At 12.5 Myr a considerable length of the EPR was simultaneously subducted beneath Baja, thus terminating subduction processes along this segment10. By 3.5 Myr the locus of transcurrent faulting had switched from the west of Baja to within the developing Gulf of California, coupling Baja to the Pacific plate11–13. We present here data for Holocene volcanic rocks from Baja California Norte which show that post-ridge subduction volcanism has a distinctive geochemistry. These results have important consequences for the interpretation of ancient orogenic belts.

Annals of the Labouring Poor: Social Change and Agrarian England, 1660-1900

Abstract: Contents: Preface; Introduction; 1. Agricultural seasonal unemployment, the standard of living, and women's work, 1690-1860; 2. Social relations - the decline of service; 3. Social relations - the poor law; 4. Enclosure and employment - the social consequences of enclosure; 5. The decline of apprenticeship; 6. The apprenticeship of women; 7. The family; 8. Thomas Hardy, rural Dorset, and the family; Appendix; Bibliography; Index.

Application of the kinematical shakedown theorem to rolling and sliding point contacts

Abstract: I n the plane-strain conditions of a long cylinder in rolling line contact with an elastic-perfectly-plastic half-space an exact shakedown limit has been established previously by use of both the statical (lower bound) and kinematical (upper bound) shakedown theorems. At loads above this limit incremental strain growth or “ratchetting” takes place by a mechanism in which surface layers are plastically sheared relative to the subsurface material. In this paper the kinematical shakedown theorem is used to investigate this mode of deformation for rolling and sliding point contacts, in which a Hertz pressure and frictional traction act on an elliptical area which repeatedly traverses the surface of a half-space. Although a similar mechanism of incremental collapse is possible, the behaviour is found to be different from that in two-dimensional line contact in three significant ways: (i) To develop a mechanism for incremental growth the plastic shear zone must spread to the surface at the sides of the contact so that a complete segment of material immediately beneath the loaded area is free to displace relative to the remainder of the half-space, (ii) Residual shear stresses orthogonal to the surface are developed in the subsurface layers, (iii) A range of loads is found in which a closed cycle of alternating plasticity takes place without incremental growth, a condition often referred to as “plastic shakedown”. Optimal upper bounds to both the elastic and plastic shakedown limits have been found for varying coefficients of traction and shapes of the loaded ellipse. The analysis also gives estimates of the residual orthogonal shear stresses which are induced.

A study of the prevalence of eye disease in the elderly in an English community.

Abstract: A randomly selected age-stratified sample of subjects 76 years of age and older living in the Melton Mowbray area was examined by an ophthalmologist and an ophthalmic optician. Over a two-year period 484 subjects were examined, with a response rate of 71.5 per cent. The prevalence rates for the major sight threatening conditions in the elderly were determined: senile cataract 46.1 per cent, senile macular degeneration 41.5 per cent and open angle glaucoma 6.6 per cent. These figures are compared to the results of other epidemiological surveys of the elderly.

Analysis of the 5′ regulatory region of the gene for δ-aminolevulinic acid synthetase of Rhizobium meliloti

Abstract: Transcriptional regulation of the delta-aminolevulinic acid synthetase gene of Rhizobium meliloti was investigated under conditions of normal vegetative growth and during symbiosis with the legume host alfalfa. S1 nuclease mapping and DNA sequence analysis indicated that transcription originates from two sites separated by 238 base pairs. A deletion analysis of the putative promoter regions P1 and P2, corresponding to the proximal and distal RNA start sites, was carried out with Bal-31 nuclease. Promoter function was monitored as beta-galactosidase activity after fusing the deletions to lac Z and introducing them into Rhizobium on a broad host range plasmid. The data obtained suggest that both regions function equivalently as promoters. The DNA sequences of P1 and P2 show considerable homology in the region between -35 and the start of transcription. Both contain a -35 region that is analogous to the consensus E. coli promoter sequence, while the -10 region is dissimilar. No resemblance was found between either P1 or P2 and the promoter regions of genes under general nitrogen control.

Oral infection of aedes aegypti with yellow fever virus: geographic variation and genetic considerations

Abstract: Twenty-eight populations representing a worldwide distribution of Aedes aegypti were tested for their ability to become orally infected with yellow fever virus (YFV). Populations had been analyzed for genetic variations at 11 isozyme loci and assigned to one of 8 genetic geographic groups of Ae. aegypti. Infection rates suggest that populations showing isozyme genetic relatedness also demonstrate similarity to oral infection rates with YFV. The findings support the hypothesis that genetic variation exists for oral susceptibility to YFV in Ae. aegypti.

Genetical and functional organisation of the Escherichia coli haemolysin determinant 2001

Abstract: We have identified gene products corresponding to hlyC, hlyA and hlyD encoded by the Escherichia coli haemolytic determinant 2001 of human origin cloned into the recombinant plasmid pLG570. The product of hlyC is required for the "activation" of the inactive 107K polypeptide encoded by the hlyA gene. The activated 107K protein constitutes the active haemolysin secreted into the medium. hlyB and hlyD are separate regions defined by complementation studies and encode functions essential for the export of haemolysin with hlyD encoding a 53K protein. Complementation studies using subclones and Tn5 insertions into pLG570 have revealed the presence of two major promoters upstream of hlyC and hlyD which transcribe the four hly genes in the same direction. Finally, we were able to reconstitute the complete haemolysin system from three different plasmids encoding hlyC, hlyA and hlyB + hlyD, respectively.

Mechanism of transient inhibition of DNA synthesis in ultraviolet-irradiated E. coli: inhibition is independent of recA whilst recovery requires RecA protein itself and an additional, inducible SOS function.

Abstract: The mechanism of the inhibition and of the recovery of DNA synthesis in E. coli following UV-irradiation was analysed in several mutants defective in repair or in the regulation of the RecA-LexA dependent SOS response. Several lines of evidence indicated that inhibition is not an inducible function and is probably due to the direct effect of lesions in the template blocking replisome movement. Recovery of DNA synthesis after UV was largely unaffected by mutations in the uvrA, recB or umuC genes. Resumption of DNA synthesis does however require protein synthesis and the regulatory action of recA. Experiments with a recA constitutive mutant and recA 200 (temperature sensitive RecA) demonstrated that RecA protein itself is directly required but is not sufficient for recovery of DNA synthesis. We therefore propose that recovery of DNA synthesis depends upon the concerted activity of RecA and the synthesis of an inducible Irr (induced replisome reactivation) factor under RecA control. We suggest that the mechanism of recovery involves the action of Irr and RecA to promote movement of replisomes past non-instructive lesions, uncoupled from polymerisation and/or that Irr and RecA are required to promote re-initiation of a stalled replication complex downstream of a UV-lesion subsequent to such an uncoupling step.

The galactic ridge observed by Exosat

Abstract: On a utilise Exosat pour cartographier la distribution de l'energie RX dans le plan galactique. En plus de nombreuses sources ponctuelles la carte revele une crete d'emission continue, etroite qui s'etend le long du plan galactique, de chaque cote du centre galactique jusqu'a ∼40° de longitude. Son origine demeure obscure; on peut toutefois exclure une contribution importante des sources RX discretes lumineuses