Showing papers by "University of Leicester published in 1997"

Caspases: the executioners of apoptosis

Abstract: Apoptosis is a major form of cell death, characterized initially by a series of stereotypic morphological changes. In the nematode Caenorhabditis elegans, the gene ced-3 encodes a protein required for developmental cell death. Since the recognition that CED-3 has sequence identity with the mammalian cysteine protease interleukin-1 beta-converting enzyme (ICE), a family of at least 10 related cysteine proteases has been identified. These proteins are characterized by almost absolute specificity for aspartic acid in the P1 position. All the caspases (ICE-like proteases) contain a conserved QACXG (where X is R, Q or G) pentapeptide active-site motif. Capases are synthesized as inactive proenzymes comprising an N-terminal peptide (prodomain) together with one large and one small subunit. The crystal structures of both caspase-1 and caspase-3 show that the active enzyme is a heterotetramer, containing two small and two large subunits. Activation of caspases during apoptosis results in the cleavage of critical cellular substrates, including poly(ADP-ribose) polymerase and lamins, so precipitating the dramatic morphological changes of apoptosis. Apoptosis induced by CD95 (Fas/APO-1) and tumour necrosis factor activates caspase-8 (MACH/FLICE/Mch5), which contains an N-terminus with FADD (Fas-associating protein with death domain)-like death effector domains, so providing a direct link between cell death receptors and the caspases. The importance of caspase prodomains in the regulation of apoptosis is further highlighted by the recognition of adapter molecules, such as RAIDD [receptor-interacting protein (RIP)-associated ICH-1/CED-3-homologous protein with a death domain]/CRADD (caspase and RIP adapter with death domain), which binds to the prodomain of caspase-2 and recruits it to the signalling complex. Cells undergoing apoptosis following triggering of death receptors execute the death programme by activating a hierarchy of caspases, with caspase-8 and possibly caspase-10 being at or near the apex of this apoptotic cascade.

Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones

Abstract: Quorum sensing relies upon the interaction of a diffusible signal molecule with a transcriptional activator protein to couple gene expression with cell population density. In Gram-negative bacteria, such signal molecules are usually N-acylhomoserine lactones (AHLs) which differ in the structure of their N-acyl side chains. Chromobacterium violaceum, a Gram-negative bacterium commonly found in soil and water, produces the characteristic purple pigmen violacein. Previously the authors described a violacein-negative, mini-Tn5 mutant of C. violaceum (CV026) in which pigment production can be restored by incubation with supernatants from the wild-type strain. To develop this mutant as a general biosensor for AHLs, the natural C. violaceum AHL molecule was first chemically characterized. By using solvent extraction, HPLC and mass spectrometry, a single AHL, N-hexanoyl-L-homoserine lactone (HHL), was identified in wild-type C. violaceum culture supernatants which was absent from CV026. Since the production of violacein constitutes a simple assay for the detection of AHLs, we explored the ability of CV026 to respond to a series of synthetic AHL and N-acylhomocysteine thiolactone (AHT) analogues. In CV026, violacein is inducible by ail the AHL and AHT compounds evaluated with N-acyl side chains from C4 to C8 in length, with varying degrees of sensitivity. Although AHL compounds with N-acyl side chains from C10 to C14 are unable to induce violacein production, if an activating AHL (e.g. HHL) is incorporated into the agar, these long-chain AHLs can be detected by their ability to inhibit violacein production. The versatility of CV026 in facilitating detection of AHL mixtures extracted from culture supernatants and separated by thin-layer chromatography is also demonstrated. These simple bioassays employing CV026 thus greatly extend the ability to detect a wide spectrum of AHL signa molecules.

ATP-sensitive and inwardly rectifying potassium channels in smooth muscle

Abstract: The properties and roles of ATP-sensitive (KATP) and inwardly rectifying (KIR) potassium channels are reviewed. Potassium channels regulate the membrane potential of smooth muscle, which controls calcium entry through voltage-dependent calcium channels, and thereby contractility through changes in intracellular calcium. The KATP channel is likely to be composed of members of the inward rectifier channel gene family (Kir6) and sulfonylurea receptor proteins. The KIR channels do not appear to be as widely distributed as KATP channels in smooth muscle and may provide a mechanism by which changes in extracellular K+ can alter smooth muscle membrane potential, and thereby arterial diameter. The KATP channels contribute to the resting membrane conductance of some types of smooth muscle and can open under situations of metabolic compromise. The KATP channels are targets of a wide variety of vasodilators and constrictors, which act, respectively, through adenosine 3',5'-cyclic monophosphate/protein kinase A and protein kinase C. The KATP channels are also activated by a number of synthetic vasodilators (e.g., diazoxide and pinacidil) and are inhibited by the oral hypoglycemic sulfonylurea drugs (e.g., glibenclamide). Together, KATP and KIR channels are important regulators of smooth muscle function and represent important therapeutic targets.

Crystal structure of the anthrax toxin protective antigen.

Abstract: Protective antigen (PA) is the central component of the three-part protein toxin secreted by Bacillus anthracis, the organism responsible for anthrax. After proteolytic activation on the host cell surface, PA forms a membrane-inserting heptamer that translocates the toxic enzymes, oedema factor and lethal factor, into the cytosol. PA, which has a relative molecular mass of 83,000 (M(r) 83K), can also translocate heterologous proteins, and is being evaluated for use as a general protein delivery system. Here we report the crystal structure of monomeric PA at 2.1 A resolution and the water-soluble heptamer at 4.5 A resolution. The monomer is organized mainly into antiparallel beta-sheets and has four domains: an amino-terminal domain (domain 1) containing two calcium ions and the cleavage site for activating proteases; a heptamerization domain (domain 2) containing a large flexible loop implicated in membrane insertion; a small domain of unknown function (domain 3); and a carboxy-terminal receptor-binding domain (domain 4). Removal of a 20K amino-terminal fragment from domain 1 allows the assembly of the heptamer, a ring-shaped structure with a negatively charged lumen, and exposes a large hydrophobic surface for binding the toxic enzymes. We propose a model of pH-dependent membrane insertion involving the formation of a porin-like, membrane-spanning beta-barrel.

Evaluation of Y-chromosomal STRs: a multicenter study

Abstract: A multicenter study has been carried out to characterize 13 polymorphic short tandem repeat (STR) systems located on the male specific part of the human Y chromosome (DYS19, DYS288, DYS385, DYS388, DYS389I/II, DYS390, DYS391, DYS392, DYS393, YCAI, YCAII, YCAIII, DXYS156Y). Amplification parameters and electrophoresis protocols including multiplex approaches were compiled. The typing of non-recombining Y loci with uniparental inheritance requires special attention to population substructuring due to prevalent male lineages. To assess the extent of these subheterogeneities up to 3825 unrelated males were typed in up to 48 population samples for the respective loci. A consistent repeat based nomenclature for most of the loci has been introduced. Moreover we have estimated the average mutation rate for DYS19 in 626 confirmed father-son pairs as 3.2 × 10–3 (95% confidence interval limits of 0.00041–0.00677), a value which can also be expected for other Y-STR loci with similar repeat structure. Recommendations are given for the forensic application of a basic set of 7 STRs (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393) for standard Y-haplotyping in forensic and paternity casework. We recommend further the inclusion of the highly polymorphic bilocal Y-STRs DYS385, YCAII, YCAIII for a nearly complete individualisation of almost any given unrelated male individual. Together, these results suggest that Y-STR loci are useful markers to identify males and male lineages in forensic practice.

A hierarchy of authentication specifications

Abstract: Many security protocols have the aim of authenticating one agent to another. Yet there is no clear consensus in the academic literature about precisely what "authentication" means. We suggest that the appropriate authentication requirement will depend upon the use to which the protocol is put, and identify several possible definitions of "authentication". We formalize each definition using the process algebra CSP, use this formalism to study their relative strengths, and show how the model checker FDR can be used to test whether a system running the protocol meets such a specification.

Growth and convergence in a multi-country empirical stochastic solow model

Abstract: SUMMARY The paper considers international per capita output and its growth using a panel of data for 102 countries between 1960 and 1989. It sets out an explicitly stochastic Solow growth model and shows that this has quite diAerent properties from the standard approach where the output equation is obtained by adding an error term to the linearized solution of a deterministic Solow model. It examines the econometric properties of estimates of beta convergence as traditionally defined in the literature and shows that all these estimates are subject to substantial biases. Our empirical estimates clearly reflect the nature and the magnitude of these biases as predicted by econometric theory. Steady state growth rates diAer significantly across countries and once this heterogeneity is allowed for the estimates of beta are substantially higher than the consensus in the literature. But they are very imprecisely estimated and diAcult to interpret. The paper also discusses the economic implications of these results for sigma convergence. #1997 John Wiley & Sons, Ltd.

The shade avoidance syndrome: multiple responses mediated by multiple phytochromes

Abstract: In recent years, the concept of shade avoidance has provided a functional meaning to the role of the phytochrome photoreceptor family in mature plants in their natural environment, and the question of which of these phytochromes is responsible for shade avoidance reactions has inevitably been raised. Unfortunately, a misconception has arisen that phytochrome B is solely responsible for detecting the environmental signal that initiates the shade avoidance syndrome. This view is too simplistic, and is based upon a selective interpretation of the available evidence. In this short Commentary, we review the concept of the shade avoidance syndrome, show how the misconception arose, and emphasize the plurality of perception and response that is crucial to successful competition for light.

Thermal and chemical structure of the Iceland plume

Abstract: Basaltic lavas, forming thick offshore seaward-dipping reflector sequences (SDRS) and onshore igneous provinces around the North Atlantic margins, represent melting of anomalously hot mantle in the head of the ancestral Iceland plume. Some of these lavas are chemically and isotopically indistinguishable from recent Icelandic basalt, but others more closely resemble basalt erupted at normal segments of mid-ocean ridges (N-MORB). In this paper we show that Icelandic basalt and N-MORB define parallel tight arrays on a plot oflog(Nb/Y) against log(Zr/Y), with N-MORB relatively deficient in Nb. Deficiency or excess of Nb, relative to the lower bound of the Iceland array, may be expressed as ΔNb=1.74+log⁡(Nb/Y)−1.92log⁡(Zr/Y)such that Icelandic basalt has ΔNb > 0 and N-MORB has ΔNb < 0. ΔNb is a fundamental source characteristic and is insensitive to the effects of variable degrees of mantle melting, source depletion through melt extraction, crustal contamination of the magmas, or subsequent alteration. We use new and published Nb, Zr and Y data to identify the mantle sources for Palaeocene and Eocene basaltic lavas erupted around the Atlantic margins in order to deduce the thermal and compositional structure of the head of the ancestral Iceland plume. The results show that the head of the plume was zoned, with an axial zone of Icelandic mantle surrounded by a thick outer shell of anomalously hot but compositionally normal N-MORB-source mantle. The zoning is very similar in scale and character to that seen today along the Reykjanes Ridge and is difficult to reconcile with the initiation of rifting and SDRS formation through the impact of a large plume head originating solely from the lower mantle. The thick outer shell of hot, depleted upper mantle, which formed more than half the volume of the plume head, suggests that at least part of the plume originated in the thermal boundary layer at the base of the upper mantle.

Noninvasive genetic tracking of the endangered Pyrenean brown bear population.

Abstract: Pyrenean brown bears Ursus arctos are threatened with extinction Management efforts to preserve this population require a comprehensive knowledge of the number and sex of the remaining individuals and their respective home ranges This goal has been achieved using a combination of noninvasive genetic sampling of hair and faeces collected in the field and corresponding track size data Genotypic data were collected at 24 microsatellite loci using a rigorous multiple-tubes approach to avoid genotyping errors associated with low quantities of DNA Based on field and genetic data, the Pyrenean population was shown to be composed at least of one yearling, three adult males, and one adult female These data indicate that extinction of the Pyrenean brown bear population is imminent without population augmentation To preserve the remaining Pyrenean gene pool and increase genetic diversity, we suggest that managers consider population augmentation using only females This study demonstrates that comprehensive knowledge of endangered small populations of mammals can be obtained using noninvasive genetic sampling

Identification of a Major Susceptibility Locus on Chromosome 6p and Evidence for Further Disease Loci Revealed by a Two Stage Genome-Wide Search in Psoriasis

Abstract: Psoriasis is a common chronic inflammatory disorder of the skin. To further understand the pathogenesis of psoriasis we have chosen to investigate the molecular genetic basis of the disorder. We have used a two-stage approach to search the human genome for the location of genes conferring susceptibility to psoriasis, using a total of 106 affected sibling pairs identified from 68 independent families. As over a third of the extended kindreds included affected relatives besides siblings, in addition to an analysis of allele sharing between affected sibling pairs, a novel linkage strategy was applied that extracts full non-parametric information. Four principal regions of possible linkage were identified on chromosomes 2, 8, 20 (p <0.005) and markers from the MHC region at 6p21 (p <0.0000006) for which significant evidence of linkage disequilibrium was also observed (p <0.00002). Whilst data from limited case control associations exist to implicate the MHC, the results of this genome wide analysis demonstrate that, at least in the population studied, a gene or genes located within the MHC and close to the class 1 HLA loci, represent the major determinant of the genetic basis of psoriasis.

The north Atlantic igneous province

Abstract: The North Atlantic Igneous Province extends from eastern Canada to the British Isles, a pre-drift distance of almost 2000 km. The igneous rocks are predominantly basaltic, but differentiates and anatectic melts are also represented. Two major phases of igneous activity can be discerned. Phase 1 began about 62 m.y. ago with continent-based magmatism in Baffin Island, W and SE Greenland, the British Isles, and possibly central E Greenland (the Lower Basalts around Kangerlussuaq). Phase 2 began about 56 m.y. ago and is represented by seaward-dipping reflector sequences (SDRS) along the continental margins, the Main Series basalts in central E Greenland, the Greenland-Faeroes Ridge, and Iceland. Contamination by continental crust was prevalent during Phase 1 but also occurred during Phase 2, especially during the formation of the early SDRS. Although it is unnecessary to involve the continental lithosphere mantle in the formation of Phase 1 or Phase 2 magmas, it is not possible to completely exclude it. We argue that the Iceland plume played a pivotal role in the formation of the North Atlantic Igneous Province because (1) the simultaneous and widespread initiation of activity requires a major thermal event in the mantle; (2) some of the magmas associated with Phase 1 were highly magnesian, indicating that the liquids and, by implication, the mantle source regions were unusually hot; (3) the SDRS were emplaced subaerially or into shallow water, indicating buoyant support by the mantle during rifting and breakup; and (4) the isotopic and compositional diversity recorded in present-day Icelandic basalts is observed in many of the Palaeocene sequences, after crustal contamination and pressure of melt segregation are taken into account. The widespread and simultaneous activity of Phase 1 activity requires an abnormally high mantle flux rate. This may be associated with the arrival of a start-up plume, but alternatively it represents the arrival of a pulse of hot mantle, following a period of weak plume activity during the Cretaceous. In either scenario, the igneous activity appears to have been focused along lines of weakness in the lithosphere. Phase 2 activity is closely linked to continental breakup. Forced mantle convection, caused by hot mantle flowing into the developing rift zones during continent breakup, may have led to the very high magma production rates (two to three times those observed in present-day Iceland) that formed the SDRS and associated deep crustal intrusions.

Casper: a compiler for the analysis of security protocols

Abstract: In recent years, a method for analyzing security protocols using the process algebra CSP (C.A.R. Hoare, 1985) and its model checker FDR (A.W Roscoe, 1994) has been developed. This technique has proved successful, and has been used to discover a number of attacks upon protocols. However the technique has required producing a CSP description of the protocol by hand; this has proved tedious and error prone. We describe Casper, a program that automatically produces the CSP description from a more abstract description, thus greatly simplifying the modelling and analysis process.

Crystal structure of the breakage-reunion domain of DNA gyrase

Abstract: DNA gyrase is a type II DNA topoisomerase from bacteria that introduces supercoils into DNA1,2. It catalyses the breakage of a DNA duplex (the G segment), the passage of another segment (the T segment) through the break, and then the reunification of the break. This activity involves the opening and closing of a series of molecular ‘gates’ which is coupled to ATP hydrolysis. Here we present the crystal structure of the ‘breakage–reunion’ domain of the gyrase at 2.8 A resolution. Comparison of the structure of this 59K (relative molecular mass, 59,000) domain with that of a 92K fragment of yeast topoisomerase II (ref. 3) reveals a very different quaternary organization, and we propose that the two structures represent two principal conformations that participate in the enzymatic pathway. The gyrase structure reveals a new dimer contact with a grooved concave surface for binding the G segment and a cluster of conserved charged residues surrounding the active-site tyrosines. It also shows how breakage of the G segment can occur and, together with the topoisomerase II structure, suggests a pathway by which the T segment can be released through the second gate of the enzyme. Mutations that confer resistance to the quinolone antibacterial agents cluster at the new dimer interface, indicating how these drugs might interact with the gyrase–DNA complex.

The y chromosome in forensic analysis and paternity testing

Abstract: The male specificity of the human Y chromosome makes it potentially useful in forensic studies and paternity testing, and markers are now available which will allow its usefulness to be assessed in practice. However, while it can be used confidently for exclusions, the unusual properties of the Y mean that inclusions will be very difficult to make: haplotypes are confined within lineages, so population sub-structuring is a major problem, and many male relatives of a suspect will share his Y chromosome. Y haplotyping is most likely to find application in special instances, such as deficiency cases in paternity testing and in the analysis of mixtures of male and female DNA, or in combination with autosomal markers.

The role of trapped space charges in the electrical aging of insulating materials

Abstract: An investigation of the effect of trapped space charges on the aging of polymeric insulating materials subjected to thermo-electrical stress is reported in this paper. Possible scenarios of degradation mechanisms, thermally activated, but accelerated by the presence of space charges, are examined. The model which derives from this approach has some interesting features: it is characterized by electrical and thermal thresholds, its parameters have a physical background, it can be cast into a probabilistic framework. Acceleration of aging due to space charges is attributed to a reduction of the free-energy barrier to degradation, seen as a local partially-reversible reaction, which is caused by energy stored in space-charge centers. The validity of the model is limited to dc voltage, and to the time of formation of microcavity-crazes, rather than to breakdown times, since other mechanisms will occur under electrical field once large enough cavities are formed in the insulation. The model is applied to the results of thermo-electrical life tests performed on PET, showing very good fitting, as well as interesting relationships between parameter estimates and insulation morphology. It is shown that the model can also fit well to ac life data, where it takes on a phenomenological meaning.

Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden

Abstract: Objective: To evaluate the disease burden of upper respiratory infections in elderly people living at home. Design: Prospective surveillance of elderly people. Intervention: None. Setting: Leicestershire, England Subjects: 533 subjects 60 to 90 years of age. Main outcome measures: Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death. Results: 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (χ 2 test P Conclusions: Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza. Key messages There are few data on the morbidity associated with respiratory viruses other than influenza in elderly people Respiratory virus infections in elderly people are clinically indistinguishable, and patients with influenza will be difficult to target for antiviral treatment without a near patient diagnostic test Overall, two thirds of elderly people with colds and four fifths of those with influenza and respiratory syncytial virus can be expected to develop lower respiratory illness Although influenza and respiratory syncytial virus cause substantial morbidity in elderly people, the disease burden from rhinovirus infections and colds of unknown aetiology is greater overall Most elderly patients seek medical attention beyond 48 hours when the benefits of antiviral treatment of influenza remain unproved

Shisha Pangma leucogranite, south Tibetan Himalaya: Field relations, geochemistry, age, origin, and emplacement

Abstract: The Shisha Pangma pluton forming most of the Xixabangma (8027 m) massif in south Tibet is one of the 20+ larger leucogranite intrusives that mark the highest structural levels of the Himalayan metamorphic core. The pluton occurs immediately below the Shisha Pangma Detachment, a strand of the South Tibetan Detachment (STD) system, a low angle (30°) north‐dipping normal fault placing Paleozoic black slates atop sillimanite‐grade pelites and calc‐silicate rocks. K‐feldspar augen gneisses containing fibrolite and sillimanite paragneisses along the footwall show strong internal S‐C fabrics indicative of down‐to‐the‐north extension. The Shisha Pangma leucogranite is a heterogeneous, polyphase intrusion with an earlier, foliated biotite‐rich phase and a later, tourmaline + muscovite rich phase typically containing the assemblage: Kfs + Pl + Qtz + Ms + Tur ± Gt ± Bt ± Sil ± Ap. The highly peraluminous granites have high 87Sr/86Sr ratios (0.738‐0.750) typical of pelite‐derived anatectites. Nd‐depleted mantle model...

Chromosome Y microsatellites: population genetic and evolutionary aspects.

Abstract: By means of a multicenter study, a large number of males have been characterized for Y-chromosome specific short tandem repeats (STRs) or microsatellites. A complete summary of the allele frequency distributions for these Y-STRs is presented in the Appendix. This manuscript describes in more detail some of the population genetic and evolutionary aspects for a restricted set of seven chromosome Y STRs in a selected number of population samples. For all the chromosome Y STRs markedly different region-specific allele frequency distributions were observed, also when closely related populations were compared. Haplotype analyses using AMOVA showed that when four different European male groups (Germans, Dutch, Swiss, Italians) were compared, less than 10% of the total genetic variability was due to differences between these populations. Nevertheless, these pairwise comparisons revealed significant differences between most population pairs. Assuming a step-wise mutation model and a mutation frequency of 0.21%, it was estimated that chromosome Y STR-based evolutionary lines of descent can be reliably inferred over a time-span of only 1950 generations (or about 49000 years). This reduces the reliability of the inference of population affinities to a historical, rather than evolutionary time scale. This is best illustrated by the construction of a human evolutionary tree based on chromosome Y STRs in which most of the branches connect in a markedly different way compared with trees based on classical protein polymorphisms and/or mtDNA sequence variation. Thus, the chromosome Y STRs seem to be very useful in comparing closely related populations which cannot probably be separated by e.g. autosomal STRs. However, in order to be used in an evolutionary context they need to be combined with more stable Y-polymorphisms e.g. base-substitutions.

Natural variation in a Drosophila clock gene and temperature compensation.

Abstract: The threonine-glycine (Thr-Gly) encoding repeat within the clock gene period of Drosophila melanogaster is polymorphic in length. The two major variants (Thr-Gly)17 and (Thr-Gly)20 are distributed as a highly significant latitudinal cline in Europe and North Africa. Thr-Gly length variation from both wild-caught and transgenic individuals is related to the flies' ability to maintain a circadian period at different temperatures. This phenomenon provides a selective explanation for the geographical distribution of Thr-Gly lengths and gives a rare glimpse of the interplay between molecular polymorphism, behavior, population biology, and natural selection.

The Arabidopsis MALE STERILITY 2 protein shares similarity with reductases in elongation/condensation complexes

Abstract: The Arabidopsis thaliana MALE STERILITY 2 (MS2) gene product is involved in male gametogenesis. The first abnormalities in pollen development of ms2 mutants are seen at the stage in microsporogenesis when microspores are released from tetrads. Expression of the MS2 gene is observed in tapetum of wild-type flowers at, and shortly after, the release of microspores from tetrads. The MS2 promoter controls GUS expression at a comparable stage in the tapetum of transgenic tobacco containing an MS2 promoter-GUS fusion. The occasional pollen grains produced by mutant ms2 plants have very thin pollen walls. They are also sensitive to acetolysis treatment, which is a test for the presence of an exine layer. The MS2 gene product shows sequence similarity to a jojoba protein that converts wax fatty acids to fatty alcohols. A possible function of the MS2 protein as a fatty acyl reductase in the formation of pollen wall substances is discussed.

The human type I collagen mutation database

Abstract: Type I collagen is the most abundant and ubiquitously distributed of the collagen family of proteins. It is a heterotrimer comprising two alpha1(I) chains and one alpha2(I) chain which are encoded by the unlinked loci COL1A1 and COL1A2 respectively. Mutations at these loci result primarily in the connective tissue disorders osteogenesis imperfecta and Ehlers-Danlos syndrome types VIIA and VIIB. Two instances of osteoporosis and a single instance of Marfan syndrome are also the result of mutations at these loci. The mutation data are accessible on the world wide web at http://www.le.ac.uk/depts/ge/collagen/collagen.html

The effects of age, gender and computer experience upon computer attitudes

Abstract: Summary The effects of age, gender and prior computing experience upon attitudes towards computers were investigated in 278 secondary school pupils drawn from the 11‐12 and 15‐16 years age‐groups. Males from both age‐groups reported greater experience with and more positive attitudes towards computers than females. Younger pupils, both male and female, were found to have greater experience with and more positive attitudes towards computers than older pupils. After controlling for ownership and use of a home computer by means of analyses of covariance, female and male pupils reported similar levels of enjoyment of computers, but age differences in enjoyment and gender and age differences in confidence with computers remained significant. Similar analyses using length of experience as a covariate did not significantly affect gender or age differences. The need to investigate and address the level of confidence of female pupils is briefly discussed.

Glucose-Induced Protein Kinase C Activation Regulates Vascular Permeability Factor mRNA Expression and Peptide Production by Human Vascular Smooth Muscle Cells In Vitro

Abstract: Hyperglycemia is an independent risk factor for the development of diabetic microvascular disease. Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. VPF is produced by many cell types, including vascular smooth muscle (VSM) cells, and has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes. This study used cultured human VSM cells to study the regulation of VPF production and determine whether elevated glucose concentrations, per se, are a sufficient stimulus for increased VPF production by human cells. In human VSM cells, high extracellular glucose concentrations (20 mmol/l) increased VPF mRNA expression within 3 h (3-fold vs. glucose 5 mmol/l) and significantly increased VPF peptide production within 24 h (1.5-fold) in a time- and glucose concentration-dependent manner. The high glucose-induced increase in VPF mRNA expression was rapidly reversed after normalizing the extracellular glucose concentration and was specific for a high D-glucose concentration, as these effects were not reproduced by osmotic control media containing elevated concentrations of mannitol or L-glucose. High glucose concentrations activate protein kinase C (PKC) in human VSM cells, and PKC inhibitors (H-7 or chelerythrine chloride) or PKC downregulation each prevented the glucose-induced increases in VPF mRNA expression by human VSM cells. In conclusion, high glucose concentrations directly increase VPF mRNA expression and peptide production by human VSM cells via a PKC-dependent mechanism. These results demonstrate a cellular mechanism, whereby hyperglycemia could directly contribute to the development of endothelial dysfunction and neovascularization in diabetes.

Relaxation of TiO 2 ( 110 ) -( 1 × 1 ) Using Surface X-Ray Diffraction

Abstract: Surface x-ray diffraction has been used to determine the structural relaxations of ${\mathrm{TiO}}_{2}(110)\ensuremath{-}(1\ifmmode\times\else\texttimes\fi{}1)$. The magnitudes range from 0 to 0.27 \AA{}, leading to rumpling of the titanium planes. The data are compared to the results of three independent calculations of the energy minimized structure. Excellent agreement is achieved with the positions of titanium atoms predicted by Ramamoorthy et al. [Phys. Rev. B 49, 16 721 (1994)].