Showing papers by "University of Leicester published in 1998"
TL;DR: It is reported here that vitamin C administered as a dietary supplement to healthy humans exhibits a pro-oxidant, as well as an antioxidant, effect in vivo.
Abstract: Vitamin C is marketed as a dietary supplement, partly because of its 'antioxidant' properties. However, we report here that vitamin C administered as a dietary supplement to healthy humans exhibits a pro-oxidant, as well as an antioxidant, effect in vivo.
782 citations
TL;DR: In this article, the authors show that NMORB and the depleted MORB mantle reservoir are characterised by a similarly limited range in / ratios and suggest that the high / MORB-like basalts may ultimately be related to mantle plumes and represent melts of a depleted component entrained by the plumes.
666 citations
TL;DR: The first cytological investigation of seed development following interploidy crosses in Arabidopsis thaliana is presented, finding that crosses between diploid and tetraploid plants in either direction, resulting in double the normal dose of maternal or paternal genomes in the seed, produce viable seeds containing triploid embryos.
Abstract: Many flowering plants are polyploid, but crosses between individuals of different ploidies produce seeds that develop abnormally and usually abort. Often, seeds from interploidy crosses develop differently depending on whether the mother or father contributes more chromosome sets, suggesting that maternal and paternal genomes are not functionally equivalent. Here we present the first cytological investigation of seed development following interploidy crosses in Arabidopsis thaliana. We find that crosses between diploid and tetraploid plants in either direction, resulting in double the normal dose of maternal or paternal genomes in the seed, produce viable seeds containing triploid embryos. However, development of the seed and in particular the endosperm is abnormal, with maternal and paternal genomic excess producing complementary phenotypes. A double dose of maternal genomes with respect to paternal contribution inhibits endosperm development and ultimately produces a smaller embryo. In contrast, a double dose of paternal genomes promotes growth of the endosperm and embryo. Reciprocal crosses between diploids and hexaploids, resulting in a triple dose of maternal or paternal genomes, produce seeds that begin development with similar but more extreme phenotypes than those with a double dose, but these invariably abort. One explanation of our observations is that seeds with maternal or paternal excess contain different doses of maternally or paternally expressed imprinted loci affecting endosperm development.
557 citations
TL;DR: This paper aims to summarise the current “state-of-play” for convergence assessment techniques and to motivate directions for future research in this area.
Abstract: MCMC methods have effectively revolutionised the field of Bayesian statistics over the past few years. Such methods provide invaluable tools to overcome problems with analytic intractability inherent in adopting the Bayesian approach to statistical modelling.
However, any inference based upon MCMC output relies critically upon the assumption that the Markov chain being simulated has achieved a steady state or ’’converged‘‘. Many techniques have been developed for trying to determine whether or not a particular Markov chain has converged, and this paper aims to review these methods with an emphasis on the mathematics underpinning these techniques, in an attempt to summarise the current ’’state-of-play‘‘ for convergence assessment techniques and to motivate directions for future research in this area.
464 citations
TL;DR: Casper is described, a program that automatically produces the CSP description from a more abstract description, thus greatly simplifying the modelling and analysis process.
Abstract: In recent years, a method for analyzing security protocols using the process algebra CSP (Hoare, 1985) and its model checker FDR (Roscoe, 1994) has been developed. This technique has proved remarkably 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 hands this has proved tedious and error-prone. In this paper we describe Casper, a program that automatically produces the CSP description from a more abstract description, thus greatly simplifying the modelling and analysis process.
425 citations
TL;DR: A view of natural elements was found to buffer the negative impact of job stress on intention to quit and to have a similar, albeit marginal, effect on general well-being.
Abstract: This article investigates the direct and indirect effects of windows in the workplace onjob satisfaction, intention to quit, and general well-being. The impact of three specific influencing mechanisms are examined: general level of illumination, sunlight penetration, and view. The extent to which these environmental features might moderate the negative consequences of job stress is investigated. The sample consisted of 100 white-and blue-collar workers who were employed in a large wine-producing organization in the Mediterranean region of Southern Europe. The results showed a significant direct effect for sunlight penetration on job satisfaction, intention to quit, and general well-being. A view of natural elements (i.e., trees, vegetation, plants, and foliage) was found to buffer the negative impact of job stress on intention to quit and to have a similar, albeit marginal, effect on general well-being. No effects for general level of illumination were found.
424 citations
TL;DR: Although present-day soda lakes are geologically quite recent, they have probably existed since archaean times, permitting the evolution of independent communities of alkaliphiles since an early period in the Earth's history.
Abstract: Soda lakes are highly alkaline extreme environments that form in closed drainage basins exposed to high evaporation rates. Because of the scarcity of Mg2+ and Ca2+ in the water chemistry, the lakes become enriched in CO3
2− and Cl−, with pHs in the range 8 to >12. Although there is a clear difference in prokaryotic communities between the hypersaline lakes where NaCl concentrations are >15% w/v and more dilute waters, i.e., NaCl concentrations about 5% w/v, photosynthetic primary production appears to be the basis of all nutrient recycling. In both the aerobic and anaerobic microbial communities the major trophic groups responsible for cycling of carbon and sulfur have in general been identified. Systematic studies have shown that the microbes are alkaliphilic and many represent separate lineages within accepted taxa, while others show no strong relationship to known prokaryotes. Although alkaliphiles are widespread it seems probable that these organisms, especially those unique to the hypersaline lakes, evolved separately within an alkaline environment. Although present-day soda lakes are geologically quite recent, they have probably existed since archaean times, permitting the evolution of independent communities of alkaliphiles since an early period in the Earth's history.
416 citations
395 citations
TL;DR: In this article, the relationship between corporate social responsibility (CSR) and the economic performance of corporations was investigated. But, the relationships were weak and lacked an overall consistency, and the results supported the conclusion that (past, concurrent and subsequent) economic performance is related to both CSR performance and disclosure.
Abstract: This paper investigates the relationship between corporate social responsibility (CSR) and the economic performance of corporations. It first examines the theories that suggest a relationship between the two. To test these theories, measures of CSR performance and disclosure developed by the New Consumer Group were analysed against the (past, concurrent and subsequent to CSR performance period) economic performance of 56 large UK companies. Economic performance included: financial (return on capital employed, return on equity and gross profit to sales ratios); and capital market performance (systematic risk and excess market valuation). The results supported the conclusion that (past, concurrent and subsequent) economic performance is related to both CSR performance and disclosure. However, the relationships were weak and lacked an overall consistency. For example, past economic performance was found to partly explain variations in firms’ involvement in philanthropic activities. CSR disclosure was affected (positively) by both a firm’s CSR performance and its concurrent financial performance. Involvement in environmental protection activities was found to be negatively correlated with subsequent financial performance. Whereas a firm’s policies regarding women’s positions seem to be more rewarding in terms of positive capital market responses (performance) in the subsequent period. Donations to the Conservative Party were found not to be related to companies’ (past, concurrent or subsequent) financial and/or capital performance.
394 citations
TL;DR: It is suggested that changes in the NAWM of patients with MS occur before lesions becomes evident on conventional MRI scans.
Abstract: Serial monthly magnetization transfer (MT) imaging was performed to evaluate whether a change of the normal appearing white matter (NAWM), which precedes the appearance of enhancing lesions, is seen in patients with multiple sclerosis (MS). Every 4 weeks for 3 months, 10 patients with relapsing-remitting MS were scanned with a T1-weighted sequence, 20 minutes after injection with 0.3 mmol/kg gadolinium-DTPA (Gd-DTPA). During each of the monthly sessions, MT and dual echo scans were also performed before Gd-DTPA injection. On coregistered images, the MT ratio (MTR) was measured in NAWM subsequently involved by enhancing lesions, in NAWM areas on the same slices but outside any present or future MR abnormality, and in enhancing lesions at the time of their appearance. Forty-eight new enhancing lesions with no corresponding abnormalities on previous scans were identified. Their average MTR was 33.1% (+/-8.4%). Three, 2, and 1 month before enhancement appearance, the mean MTR in NAWM, measured from areas corresponding to future enhancing lesions, was significantly lower than the mean MTR in NAWM outside enhancing areas; the MTR decreased steadily as the time when the enhanced lesion approached. These results suggest that changes in the NAWM of patients with MS occur before lesions become evident on conventional MRI scans.
391 citations
TL;DR: It is argued that employment structures are the outcome of both choice and constraint, and that this is the case for women, as well as men.
Abstract: Explanations of the persisting differences in the structure of men's and women's employment have long been debated in the social sciences. Sociological explanations have tended to stress the continuing significance of structural constraints on women's employment opportunities, which persist despite the removal of formal barriers. Neo-classical economists, in contrast, have emphasized the significance of individual choice, an argument which has been recently endorsed by C. Hakim who suggests that patterns of occupational segregation reflect the outcome of the choices made by different 'types' of women. In this paper, a previous debate relating to the explanatory utility of men's 'orientations to work' is used to argue that employment structures are the outcome of both choice and constraint, and that this is the case for women, as well as men. The argument is illustrated with evidence from cross-nationally comparative biographical interviews carried out in five countries
01 Apr 1998
TL;DR: Simultaneous pre- and postsynaptic whole-cell recording revealed that I(pCa) inactivation predominantly contributes to posttetanic depression of EPSCs, and because of its slow recovery, underlies this short-term synaptic plasticity.
Abstract: Voltage-gated calcium channels are well characterized at neuronal somata but less thoroughly understood at the presynaptic terminal where they trigger transmitter release. In order to elucidate how the intrinsic properties of presynaptic calcium channels influence synaptic function, we have made direct recordings of the presynaptic calcium current (I(pCa)) in a brainstem giant synapse called the calyx of Held. The current was pharmacologically classified as P-type and exhibited marked inactivation. The inactivation was largely dependent upon the inward calcium current magnitude rather than the membrane potential, displayed little selectivity between divalent charge carriers (Ca2+, Ba2+ and Sr+), and exhibited slow recovery. Simultaneous pre- and postsynaptic whole-cell recording revealed that I(pCa) inactivation predominantly contributes to posttetanic depression of EPSCs. Thus, because of its slow recovery, I(pCa) inactivation underlies this short-term synaptic plasticity.
TL;DR: The ability of each groove to bind different peptide motifs suggests how 14-3-3 can act in signal transduction by inducing either homodimer or heterodimer formation in its target proteins.
TL;DR: Data is shown which demonstrates that the 5′ UTR of the proto-oncogene c-myc contains an IRES, the first example of a proto- oncogene regulated in this manner and suggests that aberrant translational regulation of c- myc is likely to play a role in tumorigenesis.
Abstract: Translation in eukaryotic cells is generally initiated by ribosome scanning from the 5' end of the capped mRNA. However, initiation of translation may also occur by a mechanism which is independent of the cap structure and in this case ribosomes are directed to the start codon by an internal ribosome entry segment (IRES). Picornaviruses represent the paradigm for this mechanism, but only a few examples exist which show that this mechanism is used by eukaryotic cells. In this report we show data which demonstrate that the 5' UTR of the proto-oncogene c-myc contains an IRES. When a dicistronic reporter vector, with c-myc 5' UTR inserted between the two cistrons, was transfected into both HepG2 and HeLa cells, the translation of the downstream cistron was increased by 50-fold, demonstrating that translational regulation of c-myc is mediated through cap-independent mechanisms. This is the first example of a proto-oncogene regulated in this manner and suggests that aberrant translational regulation of c-myc is likely to play a role in tumorigenesis.
01 May 1998
TL;DR: Analysis of patch‐clamp, in situ hybridization and computer simulation techniques concludes that in mouse MNTB neurones the Kv3.1 channel contributes to the ability of these cells to lock their firing to high‐frequency inputs.
Abstract: 1. Using a combination of patch-clamp, in situ hybridization and computer simulation techniques, we have analysed the contribution of potassium channels to the ability of a subset of mouse auditory neurones to fire at high frequencies. 2. Voltage-clamp recordings from the principal neurones of the medial nucleus of the trapezoid body (MNTB) revealed a low-threshold dendrotoxin (DTX)-sensitive current (ILT) and a high-threshold DTX-insensitive current (IHT). 3. IHT displayed rapid activation and deactivation kinetics, and was selectively blocked by a low concentration of tetraethylammonium (TEA; 1 mM). 4. The physiological and pharmacological properties of IHT very closely matched those of the Shaw family potassium channel Kv3.1 stably expressed in a CHO cell line. 5. An mRNA probe corresponding to the C-terminus of the Kv3.1 channel strongly labelled MNTB neurones, suggesting that this channel is expressed in these neurones. 6. TEA did not alter the ability of MNTB neurones to follow stimulation up to 200 Hz, but specifically reduced their ability to follow higher frequency impulses. 7. A computer simulation, using a model cell in which an outward current with the kinetics and voltage dependence of the Kv3.1 channel was incorporated, also confirmed that the Kv3.1- like current is essential for cells to respond to a sustained train of high-frequency stimuli. 8. We conclude that in mouse MNTB neurones the Kv3.1 channel contributes to the ability of these cells to lock their firing to high-frequency inputs.
TL;DR: It is concluded that in conjunction with phYB and to a lesser extent with phyD, phyE functions in the regulation of the shade avoidance syndrome.
Abstract: From a screen of M2 seedlings derived from gamma-mutagenesis of seeds doubly null for phytochromes phyA and phyB, we isolated a mutant lacking phyE. The PHYE gene of the selected mutant, phyE-1, was found to contain a 1-bp deletion at a position equivalent to codon 726, which is predicted to result in a premature stop at codon 739. Immunoblot analysis showed that the phyE protein was undetectable in the phyE-1 mutant. In the phyA- and phyB-deficient background, phyE deficiency led to early flowering, elongation of internodes between adjacent rosette leaves, and reduced petiole elongation. This is a phenocopy of the response of phyA phyB seedlings to end-of-day far-red light treatments. Furthermore, a phyE deficiency attenuated the responses of phyA phyB seedlings to end-of-day far-red light treatments. Monogenic phyE mutants were indistinguishable from wild-type seedlings. However, phyB phyE double mutants flowered earlier and had longer petioles than did phyB mutants. The elongation and flowering responses conferred by phyE deficiency are typical of shade avoidance responses to the low red/far-red ratio. We conclude that in conjunction with phyB and to a lesser extent with phyD, phyE functions in the regulation of the shade avoidance syndrome.
TL;DR: A survey of chloroplast DNA diversity in populations of black alder revealed a high degree of structuring of 13 cpDNA haplotypes on a European scale which indicated that most of northern and central Europe was colonized from a refuge in the Carpathian Mountains.
Abstract: Traditionally, information on the postglacial history of plant species has been gained from the analysis of fossil pollen data. More recently, surveys of present patterns of genetic variation have given valuable insights into species phylogeography. The genus Alnus, based on fossil data, is known to have had at least four glacial refugia. A survey of chloroplast DNA (cpDNA) diversity in populations of black alder (A. glutinosa) was undertaken in order to gain more insight into its postglacial history. This revealed a high degree of structuring of 13 cpDNA haplotypes on a European scale which indicated that most of northern and central Europe was colonized from a refuge in the Carpathian Mountains. Based on the distribution of two common cpDNA haplotypes, colonization routes from this refuge can be determined. The locations of other previously identified refugia are confirmed and two formerly unconfirmed refugial areas for alder (southern Spain and Turkey) are proposed.
TL;DR: A novel approach to correct dystrophin deficiency at the post-transcriptional level by transfection of muscle cells with antisense RNA, which may in the future offer a therapeutic approach for DMD, as well as for other inherited disorders.
Abstract: Deletions and point mutations in the gene encoding the cytoskeletal protein dystrophin and its isoforms cause either the severe progressive myopathy Duchenne muscular dystrophy (DMD) or the milder Becker muscular dystrophy (BMD), largely depending on whether the reading frame is lost or maintained respectively. Frameshift mutations tend to result in a lack of dystrophin at the sarcolemma, destabilization of the membrane and degeneration of skeletal muscle. The mdx mouse is a valuable animal model of DMD as it bears a nonsense point mutation in exon 23 of the murine DMD gene leading to an absence of dystrophin expression in the muscle sarcolemma and muscular dystrophy. This report represents a novel approach to correct dystrophin deficiency at the post-transcriptional level by transfection of muscle cells with antisense RNA. Essentially, 2'- O -methyl oligoribonucleotides (2'OMeRNA) were delivered to the nuclei of primary mdx myoblasts in culture. Dystrophin expression was observed in the sarcolemma of transfected mdx myotubes after transfection by an oligonucleotide complementary to the 3' splice site of murine dystrophin intron 22. Direct sequencing of RT-PCR products from these cells revealed precise splicing of exon 22 to exon 30, skipping the mutant exon and creating a novel in-frame dystrophin transcript. As patients with comparable in-frame internal deletions show relatively mild myopathic symptoms, this may in the future offer a therapeutic approach for DMD, as well as for other inherited disorders.
TL;DR: Arterial K+ channels are modulated by physiological vasodilators, which increase K+ channel activity, and vasoconstrictors, which decrease it, which makes important contributions to the regulation of blood flow.
Abstract: Potassium channels play an essential role in the membrane potential of arterial smooth muscle, and also in regulating contractile tone. Four types of K+ channel have been described in vascular smooth muscle: Voltage-activated K+ channels (Kv) are encoded by the Kv gene family, Ca(2+)-activated K+ channels (BKCa) are encoded by the slo gene, inward rectifiers (KIR) by Kir2.0, and ATP-sensitive K+ channels (KATP) by Kir6.0 and sulphonylurea receptor genes. In smooth muscle, the channel subunit genes reported to be expressed are: Kv1.0, Kv1.2, Kv1.4-1.6, Kv2.1, Kv9.3, Kv beta 1-beta 4, slo alpha and beta, Kir2.1, Kir6.2, and SUR1 and SUR2. Arterial K+ channels are modulated by physiological vasodilators, which increase K+ channel activity, and vasoconstrictors, which decrease it. Several vasodilators acting at receptors linked to cAMP-dependent protein kinase activate KATP channels. These include adenosine, calcitonin gene-related peptide, and beta-adrenoceptor agonists. beta-adrenoceptors can also activate BKCa and Kv channels. Several vasoconstrictors that activate protein kinase C inhibit KATP channels, and inhibition of BKCa and Kv channels through PKC has also been described. Activators of cGMP-dependent protein kinase, in particular NO, activate BKCa channels, and possibly KATP channels. Hypoxia leads to activation of KATP channels, and activation of BKCa channels has also been reported. Hypoxic pulmonary vasoconstriction involves inhibition of Kv channels. Vasodilation to increased external K+ involves KIR channels. Endothelium-derived hyperpolarizing factor activates K+ channels that are not yet clearly defined. Such K+ channel modulations, through their effects on membrane potential and contractile tone, make important contributions to the regulation of blood flow.
TL;DR: In this paper, the authors show that the light curves of soft X-ray transients (SXTs) follow naturally from the disc instability picture, adapted to take account of irradiation by the central Xray source during the outburst.
Abstract: We show that the light curves of soft X-ray transients (SXTs) follow naturally from the disc instability picture, adapted to take account of irradiation by the central X-ray source during the outburst. Irradiation prevents the disc from returning to the cool state until central accretion is greatly reduced. This happens only after most of the disc mass has been accreted by the central object, on a viscous time-scale, accounting naturally for the exponential decay of the outburst on a far longer time-scale (τ20–40 d) than seen in dwarf novae, without any need to manipulate the viscosity parameter α. The accretion of most of the disc mass in outburst explains the much longer recurrence time of SXTs compared with dwarf novae. This picture also suggests an explanation of the secondary maximum seen in SXT light curves about 50–75 d after the start of each outburst, since central irradiation triggers the thermal instability of the outer disc, adding to the central accretion rate one viscous time later. The X-ray outburst decay constant τ should on average increase with orbital period, but saturate at a roughly constant value ∼40 d for orbital periods longer than about a day. The bolometric light curve should show a linear rather than an exponential decay at late times (a few times τ). Outbursts of long-period systems should be entirely in the linear decay regime, as is observed in GRO J1744−28. UV and optical light curves should resemble the X-rays but have decay time-scales up to 2–4 times longer.
TL;DR: The Cenomanian-Turonian boundary (90.4 Ma) represents a major period of worldwide environmental disturbance as discussed by the authors, leading to the formation of oceanic black shales and the extinction of 26% of all genera.
Abstract: The Cenomanian–Turonian boundary (90.4 Ma) represents a major period of worldwide environmental disturbance. The physical manifestations of this are: elevated atmospheric and oceanic temperatures; a significant sea-level transgression; and a period of widespread anoxia, leading to the formation of oceanic black shales, and the extinction of 26% of all genera. Elevated δ 13 C values and enrichment of trace elements in Cenomanian–Turonian boundary sediments, combined with a reduction in 87 Sr/ 86 Sr, also imply a severe environmental perturbation. At this time oceanic crustal production rates reached their highest level of the last 100 million years. This was principally caused by extensive melting of hot mantle plumes at the base of the oceanic lithosphere, and the development of vast areas (up to 1×10 6 km 2 ) of thickened oceanic crust in the Pacific and Indian Oceans. The anomalous volcanism associated with the formation of these oceanic plateaux may have been responsible for the environmental disturbances c. 90 Ma. These eruptions would also have resulted in the emission of large quantities of CO 2 into the atmosphere, leading to global warming. Additionally, the emission of SO 2 , H 2 S, CO 2 and halogens into the oceans would have made seawater more acidic resulting in the dissolution of carbonate, and further release of CO 2 This run-away greenhouse effect was probably put into reverse, by the decline of the anomalous volcanic activity, and by increased (CO 2 -driven) productivity in oceanic surface waters,leading to increased organic carbon burial, black shale deposition, anoxia and mass extinction in the ocean basins
TL;DR: The P2 receptors that are present in endothelial cells, platelets, smooth muscle and nerves, the signalling pathways that they activate and the responses that are produced are summarized.
TL;DR: The need for the report should be justified by clearly describing the problem for which evidence of effectiveness is required, and describing the needs of the health care professionals and consumers who are to benefit from the report.
Abstract: or executive summary Background information ‘The need for the report should be justified by clearly describing the problem for which evidence of effectiveness is required, and describing the needs of the health care professionals and consumers who are to benefit from the report.’ Hypotheses tested in the review Review methods ‘The methods used should be described in sections for search strategy, inclusion criteria, assessments of relevance and validity of primary studies, data extraction, data synthesis, and investigations of differences between studies.’ Details of studies included in the review ‘... details relating to the patient groups included, mode of intervention and the outcomes assessed in each study. Details of study results, study design and other aspects of study quality and validity should also be given. Sufficient information should be provided to allow replication of the analysis.’ Details of studies excluded from the review Given reason for exclusion. Results of the review ‘The estimates of efficacy from each of the studies should be given, together with the pooled effect if this has been calculated. All results should be expressed together with CIs. The table or diagram should indicate the relative weight that each study is given in the analysis. The test for heterogeneity of study results should be given if appropriate and all investigations of the differences between the studies should be report- ed in full. As well as reporting the results in relative terms the impact of the results in absolute terms [such as absolute risk reduction (ARR) and number needed to treat (NNT) (see pages 109–10)] should be given. This permits the clinical significance and possible impact of the intervention to be assessed.’ Analysis of the robustness of the results ‘Sensitivity analyses should be performed and documented to investigate the robustness of the results where there is missing data, uncertainty about study inclusion, or where there are large studies which dominate the data synthesis.’ (see pages 209–10 for more details on sensitivity analysis).
TL;DR: It is suggested that local Ca2+ release originating from RyR channels (Ca2+ sparks) in the SR of arterial smooth muscle regulates myogenic tone in cerebral arteries solely through activation of KCa channels, which regulate membrane potential through tonic hyperpolarization, thus limiting Ca1+ entry through L‐type voltage‐dependent Ca2- channels.
Abstract: 1. The effects of inhibitors of ryanodine-sensitive calcium release (RyR) channels in the sarcoplasmic reticulum (SR) and Ca2+-dependent potassium (KCa) channels on the membrane potential, intracellular [Ca2+], and diameters of small pressurized (60 mmHg) cerebral arteries (100-200 micron) were studied using digital fluorescence video imaging of arterial diameter and wall [Ca2+], combined with microelectrode measurements of arterial membrane potential. 2. Ryanodine (10 microM), an inhibitor of RyR channels, depolarized by 9 mV, increased intracellular [Ca2+] by 46 nM and constricted pressurized (to 60 mmHg) arteries with myogenic tone by 44 micron (approximately 22 %). Iberiotoxin (100 nM), a blocker of KCa channels, under the same conditions, depolarized the arteries by 10 mV, increased arterial wall calcium by 51 nM, and constricted by 37 micron (approximately 19 %). The effects of ryanodine and iberiotoxin were not additive and were blocked by inhibitors of voltage-dependent Ca2+ channels. 3. Caffeine (10 mM), an activator of RyR channels, transiently increased arterial wall [Ca2+] by 136 +/- 9 nM in control arteries and by 158 +/- 12 nM in the presence of iberiotoxin. Caffeine was relatively ineffective in the presence of ryanodine, increasing [calcium] by 18 +/- 5 nM. 4. In the presence of blockers of voltage-dependent Ca2+ channels (nimodipine, diltiazem), ryanodine and inhibitors of the SR calcium ATPase (thapsigargin, cyclopiazonic acid) were without effect on arterial wall [Ca2+] and diameter. 5. These results suggest that local Ca2+ release originating from RyR channels (Ca2+ sparks) in the SR of arterial smooth muscle regulates myogenic tone in cerebral arteries solely through activation of KCa channels, which regulate membrane potential through tonic hyperpolarization, thus limiting Ca2+ entry through L-type voltage-dependent Ca2+ channels. KCa channels therefore act as a negative feedback control element regulating arterial diameter through a reduction in global intracellular free [Ca2+].
TL;DR: The crystal structure of the vWF-A1 domain at 2.3-Å resolution is reported, and analysis of the available mutagenesis data suggests that the activator botrocetin binds to the right-hand face of the domain containing helices α5 and α6.
TL;DR: The authors argue that teaching large classes is successful in China partly because of interactive techniques in classroom dialogue, but mainly because of the underlying culture of learning and argue that the dialogue about large classes needs to take cultures of learning into account and in the Chinese case to consider collectivist and Confucian values.
TL;DR: Comparison of protein profiles of fractionated C. jejuni cells grown in low- or high-iron medium indicated derepressed expression of three iron-regulated outer membrane proteins with molecular masses of 70, 75, and 80 kDa, suggesting the presence of Fur-independent iron regulation.
Abstract: The expression of iron-regulated systems in gram-negative bacteria is generally controlled by the Fur protein, which represses the transcription of iron-regulated promoters by using Fe2+ as a cofactor. Mutational analysis of the Campylobacter jejuni fur gene was carried out by generation of a set of mutant copies of fur which had a kanamycin or chloramphenicol resistance gene introduced into the regions encoding the N and C termini of the Fur protein. The mutated genes were recombined into the C. jejuni NCTC 11168 chromosome, and putative mutants were confirmed by Southern hybridization. C. jejuni mutants were obtained only when the resistance genes were transcribed in the same orientation as the fur gene. The C. jejuni fur mutant grew slower than the parental strain. Comparison of protein profiles of fractionated C. jejuni cells grown in low- or high-iron medium indicated derepressed expression of three iron-regulated outer membrane proteins with molecular masses of 70, 75, and 80 kDa. Characterization by N-terminal amino acid sequencing showed the 75-kDa protein to be identical to CfrA, a Campylobacter coli siderophore receptor homologue, whereas the 70-kDa protein was identified as a new siderophore receptor homologue. Periplasmic fractions contained four derepressed proteins with molecular masses of 19, 29, 32, and 36 kDa. The 19-kDa protein has been previously identified, but its function is unknown. The cytoplasmic fraction contained two iron-repressed and two iron-induced proteins with molecular masses of 26, 55, 31, and 40 kDa, respectively. The two iron-repressed proteins have been previously identified as the oxidative stress defense proteins catalase (KatA) and alkyl hydroperoxide reductase (AhpC). AhpC and KatA were still iron regulated in the fur mutant, suggesting the presence of Fur-independent iron regulation. Further analysis of the C. jejuni iron and Fur regulons by using two-dimensional gel electrophoresis demonstrated the total number of iron- and Fur-regulated proteins to be lower than for other bacterial pathogens.
TL;DR: The gemini pollen1 mutant was characterized in detail and shown to act gametophytically resulting in reduced transmission through both sexes, suggesting that GEMINI POLLEN1 may be required for the localization of phragmoplast activity.
Abstract: Pollen development and male gametogenesis are critically dependent upon cell polarization leading to a highly asymmetric cell division termed pollen mitosis I. A mutational approach was adopted in Arabidopsis thaliana to identify genes involved these processes. Four independent gemini pollen mutants were isolated which produce divided or twin-celled pollen. The gemini pollen1 mutant was characterized in detail and shown to act gametophytically resulting in reduced transmission through both sexes. gemini pollen1 showed an incompletely penetrant phenotype resulting in equal, unequal and partial divisions at pollen mitosis I. The division planes in gemini pollen1 were shown to be aligned with the polar axis (as in wild type) and evidence was obtained for incomplete nuclear migration, which could account for altered division symmetry. gemini pollen1 also showed division phenotypes consistent with spatial uncoupling of karyokinesis and cytokinesis suggesting that GEMINI POLLEN1 may be required for the localization of phragmoplast activity. Cell fate studies showed that in both equal and unequal divisions a vegetative cell marker gene was activated in both daughter cells. Daughter cells with a range of intermediate or hybrid vegetative/generative cell fates suggests that cell fate is quantitatively related to cell size. The potential mode of action of GEMINI POLLEN1 and its effects on cell fate are discussed in relation to proposed models of microspore polarity and cell fate determination.
TL;DR: The kinetics of 8‐oxo‐2′‐deoxyguanosine removal and processing in vivo are illustrated, for the first time in humans, suggesting a role for vitamin C in the regulation of DNA repair enzymes and thereby demonstrating a non‐scavenging antioxidant effect.
01 Jul 1998
TL;DR: Results demonstrate that transcriptional activation of lat52 is controlled by a complex of pollen-specific cis-regulatory elements which cooperate to achieve maximum levels of gene expression throughout pollen maturation.
Abstract: The tomato lat52 gene encodes an essential cysteine-rich protein preferentially transcribed in the vegetative cell during pollen maturation. Detailed analyses of the identity, organization and role of cis-regulatory elements in controlling the precise developmental and tissue-specific expression of lat52 during pollen development were performed. Analysis of a series of 5′ promoter deletion mutants stably introduced into tobacco demonstrated differential developmental activation of deletion mutants during pollen development. All major cis-regulatory elements required for pollen-specific transcription were located within the upstream region −492 to −52. This region was shown to comprise three independent activator domains A, B and C, each sufficient to activate the minimal CaMV 35S promoter in a pollen-specific manner. 5′ deletion and gain of function approaches were used to show that domain A and the previously defined motif PBII (sub-domain B1) were largely redundant in the presence of downstream sequences in mature pollen. Within domain B two novel pollen-specific sub-domains B2 and B3 were identified. Within domain C, the activity of the PBI motif (sub-domain C1) was shown to be strictly dependent upon a downstream 20 bp pollen-specific activator unit −72 to −52 (sub-domain C2), containing two novel co-dependent regulatory elements AGAAA and TCCACCATA. These results demonstrate that transcriptional activation of lat52 is controlled by a complex of pollen-specific cis-regulatory elements which cooperate to achieve maximum levels of gene expression throughout pollen maturation. Alternative models of the interaction of identified cis-regulatory elements with putative trans-acting factors within the lat52 promoter and their developmental utilization are presented.