Showing papers by "The Hertz Corporation published in 1998"
TL;DR: Transgenic plants in which ANR1 was repressed had an altered sensitivity to NO3- and no longer responded to No3--rich zones by lateral root proliferation, indicating that ANR 1 is a key determinant of developmental plasticity in Arabidopsis roots.
Abstract: The development of plant root systems is sensitive to the availability and distribution of nutrients within the soil. For example, lateral roots proliferate preferentially within nitrate (NO3-)-rich soil patches. A NO3--inducible Arabidopsis gene (ANR1), was identified that encodes a member of the MADS box family of transcription factors. Transgenic plants in which ANR1 was repressed had an altered sensitivity to NO3- and no longer responded to NO3--rich zones by lateral root proliferation, indicating that ANR1 is a key determinant of developmental plasticity in Arabidopsis roots.
1,137 citations
TL;DR: This work demonstrates that a modification of the voltage‐gated sodium channel protein recently shown to be associated with mutations of the para‐type sodium channel gene is present in certain strains of pyrethroid resistant A. gambiae, and describes a PCR‐based diagnostic test allowing its detection in the genome of single mosquitoes.
Abstract: Pyrethroid-impregnated bednets are playing an increasing role for combating malaria, especially in stable malaria areas. More than 90% of the current annual malaria incidence (c. 500 million clinical cases with up to 2 million deaths) is in Africa where the major vector is Anopheles gambiae s.s. As pyrethroid resistance has been reported in this mosquito, reliable and simple techniques are urgently needed to characterize and monitor this resistance in the field. In insects, an important mechanism of pyrethroid resistance is due to a modification of the voltage-gated sodium channel protein recently shown to be associated with mutations of the para-type sodium channel gene. We demonstrate here that one of these mutations is present in certain strains of pyrethroid resistant A. gambiae s.s. and describe a PCR-based diagnostic test allowing its detection in the genome of single mosquitoes. Using this test, we found this mutation in six out of seven field samples from West Africa, its frequency being closely correlated with survival to pyrethroid exposure. This diagnostic test should bring major improvement for field monitoring of pyrethroid resistance, within the framework of malaria control programmes.
940 citations
TL;DR: Volatiles obtained by air entrainment of aphid infested plants were more attractive to A. ervi than those from uninfested plants, in both behavioral bioassays and activity of pure compounds, which significantly increased parasitoid responses to these compounds.
Abstract: Herbivore induced release of plant volatiles mediating the foraging behavior of the aphid parasitoid Aphidius ervi was investigated using the pea aphid, Acyrthosiphon pisum, feeding on broad bean, Vicia faba. Behavioral responses were studied using an olfactometer and a wind tunnel. Volatiles obtained by air entrainment of aphid infested plants were more attractive to A. ervi than those from uninfested plants, in both behavioral bioassays. GC-EAG of both extracts showed a number of peaks associated with responses by A. ervi, but with some differences between extracts. Compounds giving these peaks were tentatively identified by GC-MS and confirmed by comparison with authentic samples on GC, using two columns of different polarity. The activity of pure compounds was further investigated by EAG and wind tunnel assays. Results showed that, of the compounds tested, 6-methyl-5-hepten-2-one was the most attractive for A. ervi females, with linalool, (Z)-3-hexen-1-yl acetate, (E)-β-ocimene, (Z)-3-hexen-1-ol, and (E)-β-farnesene all eliciting significantly more oriented flight behavior than a solvent control. Foraging experience significantly increased parasitoid responses to these compounds, with the exception of (E)-β-farnesene. Time-course GC analysis showed that feeding of A. pisum on V. faba induced or increased the release of several compounds. Release of two of these compounds (6-methyl-5-hepten-2-one and geranic acid) was not induced by the nonhost black bean aphid, Aphis fabae. During the analysis period, production of (E)-β-ocimene remained constant, but 6-methyl-5-hepten-2-one, linalool, geranic acid, and (E)-β-farnesene appeared during the first day after A. pisum infestation and increased in concentration with increasing time of aphid feeding.
446 citations
TL;DR: 4-Amino- and 4-guanidino-4H-pyran-6-carboxamides 4 and 5 related to zanamivir (GG167) are a new class of inhibitors of influenza virus sialidases and several of the most potent analogues displayed useful antiviral activity in vivo when evaluated in a mouse model of influenza A virus infection.
Abstract: 4-Amino- and 4-guanidino-4H-pyran-6-carboxamides 4 and 5 related to zanamivir (GG167) are a new class of inhibitors of influenza virus sialidases. Structure--activity studies reveal that, in general, secondary amides are weak inhibitors of both influenza A and B viral sialidases. However, tertiary amides, which contain one or more small alkyl groups, show much greater inhibitory activity, particularly against the influenza A virus enzyme. The sialidase inhibitory activities of these compounds correlate well with their in vitro antiviral efficacy, and several of the most potent analogues displayed useful antiviral activity in vivo when evaluated in a mouse model of influenza A virus infection. Carboxamides which were highly active sialidase inhibitors in vitro also showed good antiviral activity in the mouse efficacy model of influenza A infection when administered intranasally but displayed modest activity when delivered by the intraperitoneal route.
320 citations
TL;DR: The correlation between NOS activity and grade for breast cancer suggests that NO may provide a positive growth signal within the tumour microenvironment, and inhibition of NO generation in the intratumoural microenvironment may prove a useful cancer therapy by preventing angiogenesis, invasion and metastasis.
Abstract: Varied cellular expression and localisation of nitric oxide synthase (NOS) isoforms has been shown in human cancers, including tumours of the breast, ovary, stomach, cervix and central nervous system. Mapping of NOS expression within tumour tissue from breast and gastric cancers shows inducible NOS (iNOS) is expressed predominantly in stromal (macrophage and endothelial) cells, although the level of NOS activity is at least 1-2 orders of magnitude lower than the enzyme activity associated with cytotoxicity and apoptosis. There is evidence that the intratumoural environment may provide chemoattractant signals for monocyte-macrophage recruitment and their subsequent activation via expression of interleukin-4, IgE, and CD23. Such signals lead to induction of iNOS in human macrophages in vitro. The correlation between NOS activity and grade for breast cancer suggests that NO may provide a positive growth signal within the tumour microenvironment. In vivo studies showing increased growth rate, vascular density and invasiveness of a human tumour cell line transfected to constitutively express iNOS support this. Furthermore, in vivo administration of a highly selective inhibitor of iNOS limited invasion and growth rate of iNOS transfected tumours and other murine tumours expressing this isoform. Inhibition of NO generation in the intratumoural microenvironment may prove a useful cancer therapy by preventing angiogenesis, invasion and metastasis.
279 citations
TL;DR: The present work places emphasis on the integrated nature of photosynthesis and proposes that much of the respiratory ATP necessary for whole cell photosynthesis may be generated during the production of C skeletons for N assimilation.
Abstract: The purpose of this review in reanalysing the ATP:reductant balance in illuminated leaf cells is to stress that photosynthesis in vivo does not involve CO 2 fixation alone, but embraces other processes, chief among which is N assimilation. Prior to the demonstration of CO 2 fixation and photophosphorylation by isolated chloroplasts, the mitochondria were thought likely to provide all the ATP required for CO 2 fixation (discussed in Arnon et al., 1954). During the 1960s, the development of techniques for the isolation of chloroplasts able to fix CO 2 at rates approaching those of the parent tissue induced a paradigm shift, leading to the establishment of a dominant (if not unanimous) view that chloroplasts in vivo must by themselves meet all their ATP requirements. More recent studies, however, indicate that the reality lies somewhere between these two extremes. The present work places emphasis on the integrated nature of photosynthesis and proposes that much of the respiratory ATP necessary for whole cell photosynthesis may be generated during the production of C skeletons for N assimilation. Rather than considering dissipative electron transport pathways as necessary to uncouple respiratory precursor synthesis from ATP production, the present analysis emphasizes the metabolic value of ATP produced during N-linked respiration, with cellular ATP supply being tailored to ATP demand.
275 citations
TL;DR: Oligonucleotide PCR primers were designed to detect and monitor a genetically-modified Rhizobium leguminosarum bv.
Abstract: A simple and rapid procedure for direct extraction of DNA from soils was developed to yield DNA of a high purity and quality suitable for amplification using the polymerase chain reaction (PCR). Co-extracted humic material from soil was a major contaminant of DNA and methods were devised to overcome this problem. Oligonucleotide PCR primers were designed to detect and monitor a genetically-modified (GM) Rhizobium leguminosarum bv. viciae strain RSM2004 (marked with Tn5) which had become established in Rothamsted field soils. The key steps of the procedure were alkaline-SDS buffer assisted lysis of indigenous soil bacteria in a bead-beater and the purification of extracted DNA by separate PVPP and Sephadex G-75 spin-column chromatography. The mean yield from Rothamsted soil was 25±1.7 μg crude DNA g−1 wet soil (i.e. 20 μg g−1 dry soil), sheared to fragment sizes of about 22–25 kb. The recovered DNA was easier to purify and of a higher quality, as verified by PCR amplification of a 442 bp target sequence of Tn5, than DNA extracted by a hot-SDS lysis method. The detection limit was demonstrated to be one culturable cell of RSM2004 (i.e. a single copy of Tn5) 10 mg−1 soil against a background of 107 diverse non-target bacteria.
251 citations
TL;DR: In this paper, the European potential for carbon mitigation of no-till farming using results from European tillage experiments was estimated using the results of a large-scale experiment conducted in the European Union and wider Europe.
Abstract: In this paper we estimate the European potential for carbon mitigation of no-till farming using results from European tillage experiments. Our calculations suggest some potential in terms of (a) reduced agricultural fossil fuel emissions, and (b) increased soil carbon sequestration. We estimate that 100% conversion to no-till farming would be likely to sequester about 23 Tg C y(-1) in the European Union or about 43 Tg C y(-1) in the wider Europe (excluding the former Soviet Union). In addition, up to 3.2 Tg C y(-1) could be saved in agricultural fossil fuel emissions. Compared to estimates of the potential for carbon sequestration of other carbon mitigation options, no-till agriculture shows nearly twice the potential of scenarios whereby soils are amended with organic materials. Our calculations suggest that 100% conversion to no-till agriculture in Europe could mitigate all fossil fuel-carbon emissions from agriculture in Europe. However, this is equivalent to only about 4.1% of total anthropogenic CO2-carbon produced annually in Europe (excluding the former Soviet Union) which in turn is equivalent to about 0.8% of global annual anthropogenic CO2-carbon emissions.
247 citations
TL;DR: Pattern recognition approaches were developed and applied to the classification of 600 MHz 1H NMR spectra of urine from rats dosed with compounds that induced organ‐specific damage in either the liver or kidney, confirming the robust nature of the derived model.
Abstract: Pattern recognition approaches were developed and applied to the classification of 600 MHz 1 H NMR spectra of urine from rats dosed with compounds that induced organ-specific damage in either the liver or kidney Male rats were separated into groups (n = 5) and each treated with one of the following compounds; adriamycin, allyl alcohol, 2-bromoethanamine hydrobromide, hexachlorobutadiene, hydrazine, lead acetate, mercury II chloride, puromycin aminonucleoside, sodium chromate, thioacetamide, 1,1,2-trichloro-3,3,3-trifluoro-1-propene or dose vehicle Urine samples were collected over a 7 day time-course and analysed using 600 MHz 1 H NMR spectroscopy Each NMR spectrum was data-reduced to provide 256 intensity-related descriptors of the spectra Data corresponding to the periods 8-24 h, 24-32 h and 32-56 h post-dose were first analysed using principal components analysis (PCA) In addition, samples obtained 120-144 h following the administration of adriamycin and puromycin were included in the analysis in order to compensate for the late onset of glomerular toxicity Having established that toxin-related clustering behaviour could be detected in the first three principal components (PCs), three-quarters of the data were used to construct a soft independent modelling of class analogy (SIMCA) model The remainder of the data were used as a test set of the model Only three out of 61 samples in the test set were misclassified Finally as a further test of the model, data from the 1 H NMR spectra of urine from rats that had been treated with uranyl nitrate were used Successful prediction of the toxicity type of the compound was achieved based on NMR urinalysis data confirming the robust nature of the derived model © 1998 John Wiley & Sons, Ltd
238 citations
TL;DR: Resistance–management strategies implemented on cotton in Israel, and subsequently in south–western USA, have nonetheless so far succeeded in arresting the resistance treadmill in B. tabaci through a combination of increased chemical diversity, voluntary or mandatory restrictions on the use of key insecticides, and careful integration of chemical control with other pest–management options.
Abstract: For many key agricultural pests, successful management of insecticide resistance depends not only on modifying the way that insecticides are deployed, but also on reducing the total number of treatments applied. Both approaches benefit from a knowledge of the biological characteristics of pests that promote or may retard the development of resistance. For the whitefly Bemisia tabaci (Gennadius), these factors include a haplodiploid breeding system that encourages the rapid selection and fixation of resistance genes, its breeding cycle on a succession of treated or untreated hosts, and its occurrence on and dispersal from high–value crops in greenhouses and glasshouses. These factors, in conjunction with often intensive insecticide use, have led to severe and widespread resistance that now affects several novel as well as conventional control agents. Resistance–management strategies implemented on cotton in Israel, and subsequently in south–western USA, have nonetheless so far succeeded in arresting the resistance treadmill in B. tabaci through a combination of increased chemical diversity, voluntary or mandatory restrictions on the use of key insecticides, and careful integration of chemical control with other pest–management options. In both countries, the most significant achievement has been a dramatic reduction in the number of insecticide treatments applied against whiteflies on cotton, increasing the prospect of sustained use of existing and future insecticides.
201 citations
TL;DR: Results provide evidence that a general strategy for drug design when the target has a high mutation frequency is to design the inhibitor to be as closely related as possible to the natural ligands of the target.
TL;DR: In this paper, the authors studied the effect of pH on the preservation/degradation of plant derived biomolecules including ligno-cellulose in the Park Grass Experiment at Rothamsted Experimental Station, Harpenden, U.K.
TL;DR: Findings are consistent with previous findings for shear mediated signaling via the mitogen-activated protein kinase cascade and now implicate shear modulation of the Egr-1 transcription factor in this pathway.
Abstract: The primary response transcription factor, early growth response-1 (Egr-1), is rapidly activated by a variety of extracellular stimuli. Egr-1 binds to a sequence found in the promoters of genes involved in vascular injury, such as PDGF-A and tissue factor, and trans-activates their expression in endothelial cells in response to fluid shear stress. Here we show that egr-1 mRNA is increased after 30 min of flow in human aortic endothelial cell and HeLa cell cultures. Transient transfection of HeLa cells with reporter gene constructs driven by the murine or human egr-1 5' flanking sequence revealed a five- and ninefold induction, respectively, in transcriptional activity after exposure to a shear stress of 5 dynes/cm2 for 3 h. Deletion of sequences in the murine promoter containing two AP1 sites and an inhibitory Egr-1 binding sequence, did not reduce shear stress inducibility. However, progressive deletion of five serum response elements, reduced both the basal promoter activity and its capacity to be activated by shear stress. Further examination indicated that the three upstream serum response elements are predominantly responsible for shear stress activation of the egr-1 promoter. Treatment of cells with PD98059, a specific inhibitor of mitogen-activated protein kinase-1 inhibited shear stress activation of egr-1. We suggest that egr-1 activation by shear stress involves activation of Elk-1 but not c-jun activity. These data, which are consistent with previous findings for shear mediated signaling via the mitogen-activated protein kinase cascade, now implicate shear modulation of the Egr-1 transcription factor in this pathway.
TL;DR: In this paper, multivariate regression was used to identify known components within very noisy data, permitting the rapid detection of explosive materials in the presence of overlying media for security screening applications, and the error associated with the prediction is consistent from statistically reliable data (106 integrated counts) down to spectra containing in the region of 103 counts.
Abstract: Energy dispersive x-ray diffraction (EDXRD) has been developed as a tool for the detection of explosives in passenger baggage. The measured spectra result from the combined diffraction from each of the materials within a scattering volume. Multivariate regression was used to identify known components within very noisy data, permitting the rapid detection of explosive materials in the presence of overlying media for security screening applications. Explosives can be positively identified in spectra containing as few as several hundred counts and the error associated with the prediction is consistent from statistically reliable data (106 integrated counts) down to spectra containing in the region of 103 counts. This analysis can be employed in any situation where qualitative information is required from poor quality spectral data. © 1998 John Wiley & Sons, Ltd.
TL;DR: The results suggest that the defect in the Wien 133 cells is reversible, although the molecular mechanism is not clear, and have relevance to the clinical situation as a similar GPI‐negative phenotype has been reported to occur in lymphocytes following CAMPATH‐1H treatment in vivo.
Abstract: The CAMPATH-1H (CD52) antigen is a 21 000-28 000 MW glycopeptide antigen that is highly expressed on T and B lymphocytes and is coupled to the membrane by a glycosylphosphatidylinositol (GPI) anchoring structure. The humanized CAMPATH-1H anti-CD52 antibody is extremely effective at mediating depletion of both normal and tumorigenic lymphocytes in vivo and has been used in clinical trials for lymphoid malignancy and rheumatoid arthritis. Cross-linking GPI-anchored molecules, including CD52, on the surface of T lymphocytes in the presence of phorbol 12-myristate 13-acetate or anti-CD3, results in cellular activation. In the present study we have investigated the functional effects of cross-linking CD52 on T and B tumour cell lines. Cross-linking CD52 on either a B-cell line, Wien 133, which expresses high levels of endogenous CD52 or Jurkat T cells transfected and selected to express high levels of CD52 resulted in growth inhibition. This effect showed slower kinetics and occurred in a lower percentage of cells than growth inhibition stimulated via T- or B-cell receptors. Growth inhibition of the Wien 133 line was followed by the induction of apoptosis, which appeared independent of the Fas/Fas L pathway. Wien 133 cells surviving anti-CD52 treatment were selected and cloned and found to have down-regulated CD52 expression, with a characteristic biphasic pattern of 10% CD52-positive, 90% negative by fluorescence-activated cell sorter analysis. Interestingly, surface expression of other GPI-linked molecules, such as CD59 and CD55, was also down-regulated, but other transmembrane molecules such as surface IgM, CD19, CD20, HLA-DR were unaffected. The present study and previous work show that this is due to a defect in the synthesis of mature GPI precursors. Separation of CD52-positive and negative populations in vitro resulted in a rapid redistribution to the mixed population. Injection of CD52-negative cells into nude mice to form a subcutaneous tumour resulted in a substantial increase in expression of CD52. These results suggest that the defect in the Wien 133 cells is reversible, although the molecular mechanism is not clear. These observations have relevance to the clinical situation as a similar GPI-negative phenotype has been reported to occur in lymphocytes following CAMPATH-1H treatment in vivo.
TL;DR: Although the purified enzymes were unable to reduce NAD(P), electrons from both pyruvate and 2-oxoglutarate could reduce NADP in cell extracts, consistent with a role for these oxidoreductases in the provision of NADPH as a respiratory electron donor.
Abstract: Helicobacter pylori, a major cause of human gastric disease, is a microaerophilic bacterium that contains neither pyruvate nor 2-oxoglutarate dehydrogenase activity. Previous studies (N. J. Hughes, P. A. Chalk, C. L. Clayton, and D. J. Kelly, J. Bacteriol. 177:3953-3959, 1995) have indicated that the major routes for the generation of acetyl coenzyme A (acetyl-CoA) and succinyl-CoA are via pyruvate:flavodoxin oxidoreductase (POR) and 2-oxoglutarate:acceptor oxidoreductase (OOR), respectively. The purified POR is a heterotetrameric protein, with subunits of 48 (PorA), 36 (PorB), 24 (PorC), and 14 (PorD) kDa. In this study OOR has been purified, and it is similarly composed of polypeptides of 43 (OorA), 33 (OorB), 24 (OorC), and 10 (OorD) kDa. Both POR and OOR are oxygen labile and are likely to be major contributors to the microaerophilic phenotype of H. pylori. Unlike POR, OOR was unable to use a previously identified flavodoxin (FldA) as an electron acceptor. Although the purified enzymes were unable to reduce NAD(P), electrons from both pyruvate and 2-oxoglutarate could reduce NADP in cell extracts, consistent with a role for these oxidoreductases in the provision of NADPH as a respiratory electron donor. The H. pylori por, oor, and fldA genes were cloned and sequenced. The deduced por gene products showed significant sequence similarity to archaeal four-subunit 2-oxoacid:acceptor oxidoreductases. However, the amino acid sequences of OorA and -B were more closely related to that of the two-subunit POR of the aerobic halophile Halobacterium halobium. Both porD and oorD encode integral ferredoxin-like subunits. POR and OOR are probably essential enzymes in H. pylori, as insertion inactivation of porB and oorA appeared to be lethal.
TL;DR: On the basis of comparison with literature data for PEG and selected drugs, rat would appear to be a better predictor than dog of absorption of hydrophilic compounds in human.
TL;DR: The results demonstrate the difficulty in comparing total soil solution and free metal ion concentrations for soils from different areas with different physiochemical properties and sources of contamination.
TL;DR: SAR in a series of monocyclic beta-lactam N-ureas, has defined the size and relative stereochemistry of the C-3 substituent producing a low micromolar inhibitor 17b with good aqueous stability and selectivity over the mammalian serine proteases.
TL;DR: The cellular and molecular actions of LTG that may contribute to its action in bipolar disorder are described and would be expected to regulate aberrant intracellular and intercellular signalling in critical regions of the limbic forebrain where hyperactivity may occur in mania, and thus may be directly relevant to its mood-stabilising properties.
Abstract: Several clinical studies have investigated the use of the anticonvulsant lamotrigine (LTG) as a treatment for bipolar affective disorder. Evidence suggests that this drug may have a broad spectrum of
TL;DR: In this article, the authors investigated whether tropical soils developed under tropical conditions had different organic matter and microbial biomass dynamics than those developed under temperate ones and concluded that the organic matter in the tropical soils was more degraded, or humified, than that in the temperate soils.
Abstract: The aim was to investigate whether soils developed under tropical conditions had different organic matter and microbial biomass dynamics than soils developed under temperate ones. Three soils formed under temperate climatic conditions (U.K.) and three under tropical conditions (Brazilian) were selected to be as comparable as possible in terms of organic matter, clay content and pH. They were then incubated moist at 15°C or 35°C for 150 d. Carbon dioxide evolution and microbial biomass were measured at intervals during the incubation. The biomasses in the tropical soils declined more slowly at both temperatures than in the temperate soils, although at 15°C the differences were mainly small. At 35°C the decline was generally much more marked in the temperate soils (60–75% of the initial value) than in the tropical ones (15, 40 and 60%). Soil organic matter was mineralised more rapidly in the temperate than the tropical soils: at 35°C up to 9–10 times more CO 2 –C was evolved than was contained in the temperate biomasses during the 150 d incubation. The comparable maximum value for the tropical soils was 4.5 times. These results seem to indicate that the organic matter in the tropical soils was more degraded, or humified, than that in the temperate soils. An attempt to quantify the extent of humification was made using differential thermal analysis (DTA) and thermogravimetric analysis (TG). Both methods also indicated that the organic matter was generally more humified in the tropical than temperate soils. It was concluded that DTA and TG may both be useful techniques in studying soil organic matter dynamics, especially when linked to studies of soil microbial dynamics.
TL;DR: It is suggested that either apolipoprotein E is of no importance in the maintenance of synaptic integrity and in processes of CNS plasticity and repair, or more likely, alternative (apolipo)proteins may compensate for the loss of Apolipopprotein E in the knockout animals.
TL;DR: The inhibition of the p-chloroamphetamine-induced 5- HT syndrome in rats suggests that lamotrigine also inhibits 5-HT uptake in vivo, and this effects probably reflect an affinity for biogenic amine transporters.
TL;DR: The analyses of the three dimensional structure of the MMPs in the context of their primary sequence and the design and selectivity of low molecular weight inhibitors of the superfamily is the subject of this review.
Abstract: The family of proteins called matrix metalloproteinases (MMPs) are a class of structurally related proteins that are collectively responsible for the metabolism of extracellular matrix proteins. These zinc and calcium dependent enzymes, which include the collagenases, stromelysins and gelatinases, are involved in normal tissue remodelling processes such as wound healing, pregnancy and angiogenesis. Under physiological conditions, in addition to the regulated proteolyses of inactive precursors to the active form, the degradative nature of these enzymes are precisely controlled by endogenous inhibitors (TIMPs). The excess syntheses and production of these proteins lead to the accelerated matrix degradation associated with diseases such as arthritis, cancer and multiple sclerosis. The MMPs have therefore proved to be attractive targets for structure based drug design. The pursuit of low molecular weight inhibitors of these proteins have encouraged structural studies on several members of family, so that the molecular details of enzyme-inhibitor interactions of the MMPs have become available. These studies provide insights into the basic structural framework of the MMP superfamily and reveal characteristics which promote specificity between individual members. The analyses of the three dimensional structure of the MMPs in the context of their primary sequence and the design and selectivity of low molecular weight inhibitors of the superfamily is the subject of this review.
TL;DR: In this article, total lipid extracts were obtained from soil samples taken in the years 1882, 1913, 1946, 1965 and 1995 from three treatments of the Hoosfield Spring Barley Experiment at Rothamsted Experimental Station, Harpenden, Hertfordshire, U.K.
TL;DR: A region of about 800 bp of ribosomal DNA has been sequenced in 10 isolates of Polymyxa and one isolate each of Plasmodiophora Brassicae and the chytrid Olpidium brassicae, and the results supported the earlier division of P. graminis into three subgroups and the recognition ofP.
TL;DR: The vascular endothelium, lining the blood vessel wall, is constantly exposed to wall shear stresses generated by flowing blood, and gene regulation depends on complex interactions at the promoter level and utilizes overlapping signal transduction cascades to activate the expression of genes involved in many biological processes.
Abstract: The vascular endothelium, lining the blood vessel wall, is constantly exposed to wall shear stresses generated by flowing blood. Gene regulation, critical for endothelial cell function, depends on complex interactions at the promoter level and utilizes overlapping signal transduction cascades to activate the expression of genes involved in many biological processes.
TL;DR: A liquid chromatography tandem mass spectrometry (LC/MS/MS) method has been developed for the fast routine analysis of selected CYP450 probe substrate metabolites in microsomal incubations, with no sample pretreatment, providing information which can then be used to rationalize in vivo interaction studies required in the clinic.
Abstract: A liquid chromatography tandem mass spectrometry (LC/MS/MS) method has been developed for the fast routine analysis of selected CYP450 probe substrate metabolites in microsomal incubations, with no sample pretreatment. This has allowed fast and simple assessment of the potential effects which drug candidates may or may not have on the metabolism of specific CYP450 probe substrates, providing information which can then be used to rationalize in vivo interaction studies required in the clinic. This methodology takes advantage of fast gradient chromatography as a generic means of sample separation and analysis. It provides high throughput analysis compared to conventional gradient HPLC, with no significant loss in chromatographic performance. © 1998 John Wiley & Sons, Ltd.
TL;DR: This work has identified several classes of protein which bind to Drosophila PCNA and found a conserved PCNA-binding domain which is present in a human relative of Pogo, suggesting that this domain has a functional role in this class of transposable element.
Abstract: The eukaryotic polymerase processivity factor, PCNA, interacts with cell cycle regulatory proteins such as p21(WAF1/Cip1) and Gadd45, as well as with proteins involved in the mechanics of DNA repair and replication. A conserved PCNA-binding motif is found in a subset of PCNA-interacting proteins, including p21, suggesting that the regulation of these interactions is important for the co-ordination of DNA replication and repair. We have identified several classes of protein which bind to Drosophila PCNA. Two of these proteins contain the consensus PCNA-binding domain: one is the Dacapo protein, a Drosophila homologue of p21(WAF1/Cip1), and the second is the transposase encoded by the Pogo DNA transposon . A conserved PCNA-binding domain is also present in a human relative of Pogo , named Tigger , suggesting that this domain has a functional role in this class of transposable element. This raises interesting possibilities for a novel method of transposition in which the transposase might be targeted to replicating DNA. Finally, we have investigated the use of this conserved PCNA-binding domain as a predictor of PCNA-binding capacity.
TL;DR: The use of capillary electrophoresis (CE) for main component determinations, stoichiometric assays, analysis of vitamins and regulatory aspects of pharmaceutical analysis is discussed in this paper.
Abstract: Part I covered the use of capillary electrophoresis (CE) for main component determinations, stoichiometric assays, analysis of vitamins and regulatory aspects of pharmaceutical analysis. This second article examines the use of CE in the determination of drug-related impurities, chiral separations and the expanding use of capillary electrochromatography (CEC) within the pharmaceutical industry. Impurity determinations are probably the principal role of CE within pharmaceutical analysis and represent a challenge to both the selectivity and sensitivity capabilities of the technique. The main component and structurally-related impurities often have very similar chemical properties which place great requirements on the selectivity necessary. Detection limits of 0.1% area/area are widely accepted as a minimum requirement for a related impurity determination method and this is possible by CE. The use of a number of chiral selective electrolyte additives including proteins, carbohydrates, crown ethers and antibiotics are reviewed. Validation reports of chiral CE methods are discussed in comparison to high performance liquid chromatography methods. This review also examines the increasing use of CEC in the analysis of chiral compounds.