Showing papers by "Kettering University published in 1998"
TL;DR: It is concluded that CXCR-4 is expressed on CD34+ cells including more primitive, pluripotent progenitors, and may therefore play a role in the homing of hematopoietic stem cells.
657 citations
TL;DR: Three stabilising control strategies are discussed: time average control, a variable structure control, and a hybrid feedback control for quadratically stabilising the state trajectory by switching between the two unstable systems.
422 citations
TL;DR: A variety of nongerm cell histologies, including sarcoma, adenocarcinoma, primitive neuroectodermal tumor and leukemia, may occur in association with germ cell tumor, and surgical resection is the mainstay of therapy.
349 citations
TL;DR: The topoisomerase catalytic pentad is conserved in the tertiary structures of the recombinases despite scant sequence similarity overall, which implies that the catalytic domains of type IB topoisomersases and recombinase derive from a common ancestral strand transferase.
252 citations
Book•
01 Jan 1998TL;DR: In this paper, the Smith chart and its applications are discussed, as well as computer-aided analysis of electromagnetic fields and their application in computer programs for various problems, such as computer aided analysis of static fields, waveguide and cavity resonators.
Abstract: Preface 1. Electromagnetic field theory 2. Vector analysis 3. Electrostatics 4. Steady electrical currents 5. Magnetostatics 6. Applications of static fields 7. Time-varying electromagnetic fields 8. Plane wave propagation 9. Transmission lines 10. Waveguides and cavity resonators 11. Antennas 12. Computer-aided analysis of electromagnetic fields Appendix A. Smith chart and its applications Appendix B. Computer programs for various problems Appendix C. Useful mathematical tables Index.
242 citations
TL;DR: Prp22 has two distinct functions in yeast pre‐mRNA splicing: an ATP‐independent role during the second catalytic step and an ATP-requiring function in disassembly of the spliceosome.
Abstract: In order to assess the role of Prp22 in yeast pre-mRNA splicing, we have purified the 130 kDa Prp22 protein and developed an in vitro depletion/reconstitution assay. We show that Prp22 is required for the second step of actin pre-mRNA splicing. Prp22 can act on pre-assembled spliceosomes that are arrested after step 1 in an ATP-independent fashion. The requirement for Prp22 during step 2 depends on the distance between the branchpoint and the 3' splice site, suggesting a previously unrecognized role for Prp22 in splice site selection. We characterize the biochemical activities of Prp22, a member of the DExH-box family of proteins, and we show that purified recombinant Prp22 protein is an RNA-dependent ATPase and an ATP-dependent RNA helicase. Prp22 uses the energy of ATP hydrolysis to effect the release of mRNA from the spliceosome. Thus, Prp22 has two distinct functions in yeast pre-mRNA splicing: an ATP-independent role during the second catalytic step and an ATP-requiring function in disassembly of the spliceosome.
228 citations
TL;DR: A role is established for the χ subunit of the γ complex clamp loader in contacting SSB, thus enhancing the clamp loading and processivity of synthesis of the holoenzyme, presumably by helping to localize the Holoenzyme to sites of SSB‐coated ssDNA.
Abstract: Escherichia coli DNA polymerase III holoenzyme contains 10 different subunits which assort into three functional components: a core catalytic unit containing DNA polymerase activity, the beta sliding clamp that encircles DNA for processive replication, and a multisubunit clamp loader apparatus called gamma complex that uses ATP to assemble the beta clamp onto DNA. We examine here the function of the psi subunit of the gamma complex clamp loader. Omission of psi from the holoenzyme prevents contact with single-stranded DNA-binding protein (SSB) and lowers the efficiency of clamp loading and chain elongation under conditions of elevated salt. We also show that the product of a classic point mutant of SSB, SSB-113, lacks strong affinity for psi and is defective in promoting clamp loading and processive replication at elevated ionic strength. SSB-113 carries a single amino acid replacement at the penultimate residue of the C-terminus, indicating the C-terminus as a site of interaction with psi. Indeed, a peptide of the 15 C-terminal residues of SSB is sufficient to bind to psi. These results establish a role for the psi subunit in contacting SSB, thus enhancing the clamp loading and processivity of synthesis of the holoenzyme, presumably by helping to localize the holoenzyme to sites of SSB-coated ssDNA.
188 citations
TL;DR: Topical prostaglandin analogs may be relatively contraindicated in patients with a history of uveitis or prior ocular surgery and this association may also be possible in eyes that have not had previous uvesitis or incisional surgery.
157 citations
TL;DR: DR mammary adenocarcinoma MCF-7/Adr cells refractory to paclitaxel, dEpoB reduced the established tumors, markedly suppressed tumor growth, and surpassed other commonly used chemotherapy drugs such as adriamycin, vinblastine, and etoposide in beneficial effects.
Abstract: The epothilones are naturally occurring, cytotoxic macrolides that function through a paclitaxel (Taxol)-like mechanism. Although structurally dissimilar, both classes of molecules lead to the arrest of cell division and eventual cell death by stabilizing cellular microtubule assemblies. The epothilones differ in their ability to retain activity against multidrug-resistant (MDR) cell lines and tumors where paclitaxel fails. In the current account, we focus on the relationship between epothilone and paclitaxel in the context of tumors with multiple drug resistance. The epothilone analogue Z-12,13-desoxyepothilone B (dEpoB) is >35,000-fold more potent than paclitaxel in inhibiting cell growth in the MDR DC-3F/ADX cell line. Various formulations, routes, and schedules of i.v. administration of dEpoB have been tested in nude mice. Slow infusion with a Cremophor-ethanol vehicle proved to be the most beneficial in increasing efficacy and decreasing toxicity. Although dEpoB performed similarly to paclitaxel in sensitive tumors xenografts (MX-1 human mammary and HT-29 colon tumor), its effects were clearly superior against MDR tumors. When dEpoB was administered to nude mice bearing our MDR human lymphoblastic T cell leukemia (CCRF-CEM/paclitaxel), dEpoB demonstrated a full curative effect. For human mammary adenocarcinoma MCF-7/Adr cells refractory to paclitaxel, dEpoB reduced the established tumors, markedly suppressed tumor growth, and surpassed other commonly used chemotherapy drugs such as adriamycin, vinblastine, and etoposide in beneficial effects.
156 citations
TL;DR: The crystal structure of the leader protease of foot‐and‐mouth disease virus comprises a globular catalytic domain reminiscent of that of cysteine proteases of the papain superfamily, and a flexible C‐terminal extension found intruding into the substrate‐binding site of an adjacent molecule.
Abstract: The leader protease of foot-and-mouth disease virus, as well as cleaving itself from the nascent viral polyprotein, disables host cell protein synthesis by specific proteolysis of a cellular protein: the eukaryotic initiation factor 4G (eIF4G). The crystal structure of the leader protease presented here comprises a globular catalytic domain reminiscent of that of cysteine proteases of the papain superfamily, and a flexible C-terminal extension found intruding into the substrate-binding site of an adjacent molecule. Nevertheless, the relative disposition of this extension and the globular domain to each other supports intramolecular self-processing. The different sequences of the two substrates cleaved during viral replication, the viral polyprotein (at LysLeuLys/GlyAlaGly) and eIF4G (at AsnLeuGly/ArgThrThr), appear to be recognized by distinct features in a narrow, negatively charged groove traversing the active centre. The structure illustrates how the prototype papain fold has been adapted to the requirements of an RNA virus. Thus, the protein scaffold has been reduced to a minimum core domain, with the active site being modified to increase specificity. Furthermore, surface features have been developed which enable C-terminal self-processing from the viral polyprotein.
146 citations
TL;DR: Findings from a biochemical and genetic analysis of mouse mRNA capping enzyme contribute to an emerging model of mRNA biogenesis wherein RNA processing enzymes are targeted to nascent polymerase II transcripts through contacts with the CTD.
TL;DR: Findings provide genetic evidence for the long-held idea that the cap guanylate is critical for mRNA stability, as the deadenylation-decapping-degradation pathway appears to be short-circuited when Ceg1 is inactivated.
Abstract: Current models of mRNA decay in yeast posit that 3' deadenylation precedes enzymatic removal of the 5' cap, which then exposes the naked end to 5' exonuclease action. Here, we analyzed gene expression in Saccharomyces cerevisiae cells bearing conditional mutations of Ceg1 (capping enzyme), a 52 kDa protein that transfers GMP from GTP to the 5' end of mRNA to form the GpppN cap structure. Shift of ceg1 mutants to restrictive temperature elicited a rapid decline in the rate of protein synthesis, which correlated with a sharp reduction in the steady-state levels of multiple individual mRNAs. ceg1 mutations prevented the accumulation of SSA1 and SSA4 mRNAs that were newly synthesized at the restrictive temperature. Uncapped poly(A)+ SSA4 mRNA accumulated in cells lacking the 5' exoribonuclease Xrn1. These findings provide genetic evidence for the long-held idea that the cap guanylate is critical for mRNA stability. The deadenylation-decapping-degradation pathway appears to be short-circuited when Ceg1 is inactivated.
TL;DR: It is now evident from multiple crystal structures that the catalytic domains of type IB topoisomerases and site specific recombinases derive from a common ancestral strand transferase capable of forming a DNA-(3'-phosphotyrosyl)-enzyme intermediate.
TL;DR: This work has developed an alternative strategy for the isolation and enrichment of precursor cells, by fluorescence-activated cell sorting of forebrain cells transfected with the gene for green fluorescent protein, driven by the neuronal Tα1 tubulin promoter.
Abstract: Neuronal precursor cells are widespread in the forebrain ventricular/subventricular zone, and may provide a cellular substrate for brain repair Clonal lines derived from single progenitors can become progressively less representative of their parental precursors with time and passage in vitro We have developed an alternative strategy for the isolation and enrichment of precursor cells, by fluorescence-activated cell sorting of forebrain cells transfected with the gene for green fluorescent protein, driven by the neuronal T alpha 1 tubulin promoter Using this approach, neural precursors and young neurons can be identified and selectively harvested from a variety of samples, including both avian and mammalian forebrains at different developmental stages
TL;DR: The rate of survival of patients with high‐grade chondrosarcoma treated with chemotherapy is poor, and P‐glycoprotein expression is common in benign and malignant cartilage lesions, so the lack of response to chemotherapy may be related to the expression of P‐ Glycoprotein.
TL;DR: It is argued that Pipe defines the region of the embryo where ligand processing can occur, but other mechanisms determine how far the ligand can spread and where the peak of Dorsal activation will arise.
TL;DR: A stereoisomer of the natural product and not himastatin, an unusual dimeric depsipeptide with promising antibiotic and antitumor properties, was obtained from pyrroloindoline anti-cis-1 and this result led to a revision of the proposed stereostructure.
Abstract: A stereoisomer of the natural product and not himastatin, an unusual dimeric depsipeptide with promising antibiotic and antitumor properties, was obtained from pyrroloindoline anti-cis-1 This result led to a revision of the proposed stereostructure The new stereostructure was confirmed by the total synthesis, which involves stereoselective access to the pyrroloindoline syn-cis-1 and the 5-hydroxypiperazic acid subunit and features a Stille coupling for the formation of the central carbon-carbon bond
Journal Article•
TL;DR: It is concluded that a chronic high level of TPO overexpression stimulates megakaryocytopoiesis and myelopoiesi leading to thrombocytosis and granulocytotic and xenogeneic transgene delivered by adenovector to a host with normal immune functions may induce loss of immune tolerance and autoimmune phenomenon.
Abstract: Thrombopoietin (TPO) cDNA can be effectively delivered in vivo by adenovectors. Immune normal mice (BALB/c) and syngeneic mice with variable degrees of immune dysfunction nu, SCID, and NOD-SCID) were treated with an adenovirus vector expressing the human TPO cDNA (AdTPO). Platelet peaks were significantly higher in SCID and NOD-SCID mice compared with BALB/c and nu mice. Human plasma TPO concentration correlated with the platelet counts. SCID and NOD-SCID mice exhibited also granulocytosis and increased numbers of hemopoietic progenitors in bone marrow. Following platelet peak, BALB/c mice developed autoantibodies against murine TPO leading to thrombocytopenia and depletion of megakaryocytes and hemopoietic progenitors in bone marrow. AdTPO-treated SCID mice developed osteomyelofibrosis and extramedullary/extrasplenal hemopoiesis. In contrast, NOD-SCID mice with a similar magnitude of TPO overexpression did not show fibrotic changes in bone marrow. We conclude, first, that a chronic high level of TPO overexpression stimulates megakaryocytopoiesis and myelopoiesis leading to thrombocytosis and granulocytosis. Second, increased megakaryocytopoiesis is not sufficient for development of secondary osteomyelofibrosis. The functionally deficient monocytes and macrophages of NOD-SCID mice probably prevented fibrotic marrow changes. Third, immune deficiency enhances expression of adenovirally mediated transgenes, and fourth, xenogeneic transgene delivered by adenovector to a host with normal immune functions may induce loss of immune tolerance and autoimmune phenomenon.
TL;DR: Mutational analysis of the active site motif KxDGxR illuminates essential roles for the conserved Lys, Asp and Arg moieties at different steps of the ligase reaction and suggests that occupancy of the AMP binding pocket of DNA ligase is important for nick recognition.
Abstract: Chlorella virus PBCV-1 DNA ligase seals nicked DNA substrates consisting of a 5'-phosphate-terminated strand and a 3'-hydroxyl-terminated strand annealed to a bridging DNA template strand. The enzyme discriminates at the DNA binding step between substrates containing a 5'-phosphate versus a 5'-hydroxyl at the nick. Mutational analysis of the active site motif KxDGxR (residues 27-32) illuminates essential roles for the conserved Lys, Asp and Arg moieties at different steps of the ligase reaction. Mutant K27A is unable to form the covalent ligase-(Lys-straightepsilonN-P)-adenylate intermediate and hence cannot activate a nicked DNA substrate via formation of the DNA-adenylate intermediate. Nonetheless, K27A catalyzes phosphodiester bond formation at a pre-adenylated nick. This shows that the active site lysine is not required for the strand closure reaction. K27A binds to nicked DNA-adenylate, but not to a standard DNA nick. This suggests that occupancy of the AMP binding pocket of DNA ligase is important for nick recognition. Mutant D29A is active in enzyme-adenylate formation and binds readily to nicked DNA, but is inert in DNA-adenylate formation. R32A is unable to catalyze any of the three reactions of the ligation pathway and does not bind to nicked DNA.
TL;DR: Deletion analysis of the 298 amino acid Chlorella virus DNA ligase indicates that motif VI plays a critical role in the reaction of ligase with ATP to form ligase-adenylate, but is dispensable for the two subsequent steps in the ligation pathway; DNA-adenyate formation and strand closure.
Abstract: A conserved catalytic core of the ATP-dependent DNA ligases is composed of an N-terminal domain (domain 1, containing nucleotidyl transferase motifs I, III, IIIa and IV) and a C-terminal domain (domain 2, containing motif VI) with an intervening cleft. Motif V links the two structural domains. Deletion analysis of the 298 amino acid Chlorella virus DNA ligase indicates that motif VI plays a critical role in the reaction of ligase with ATP to form ligase-adenylate, but is dispensable for the two subsequent steps in the ligation pathway; DNA-adenylate formation and strand closure. We find that formation of a phosphodiester at a pre-adenylated nick is subject to a rate limiting step that does not apply during the sealing of nicked DNA by ligase-adenylate. This step, presumably conformational, is accelerated or circumvented by deleting five amino acids of motif VI. The motif I lysine nucleophile (Lys27) is not required for strand closure by wild-type ligase, but this residue enhances the closure rate by a factor of 16 when motif VI is truncated. We find that a more extensively truncated ligase consisting of only N-terminal domain 1 and motif V is inert in ligase--adenylate formation, but competent to catalyze strand closure at a pre-adenylated nick. These results suggest that different enzymic catalysts facilitate the three steps of the DNA ligase reaction.
TL;DR: The findings indicate that Chlorella virus DNA ligase has the potential to affect genome integrity by embedding ribonucleotides in viral DNA and by sealing nicked molecules with mispaired ends, thereby generating missense mutations.
Abstract: Chlorella virus PBCV-1 DNA ligase seals nicked duplex DNA substrates consisting of a 5'-phosphate-terminated strand and a 3'-hydroxyl-terminated strand annealed to a bridging template strand, but cannot ligate a nicked duplex composed of two DNAs annealed on an RNA template. Whereas PBCV-1 ligase efficiently joins a 3'-OH RNA to a 5'-phosphate DNA, it is unable to join a 3'-OH DNA to a 5'-phosphate RNA. The ligase discriminates at the substrate binding step between nicked duplexes containing 5'-phosphate DNA versus 5'-phosphate RNA strands. PBCV-1 ligase readily seals a nicked duplex DNA containing a single ribonucleotide substitution at the reactive 5'-phosphate end. These results suggest a requirement for a B-form helical conformation of the polynucleotide on the 5'-phosphate side of the nick. Single base mismatches at the nick exert disparate effects on DNA ligation efficiency. PBCV-1 ligase tolerates mismatches involving the 5'-phosphate nucleotide, with the exception of 5'-A:G and 5'-G:A mispairs, which reduce ligase activity by two orders of magnitude. Inhibitory configurations at the 3'-OH nucleotide include 3'-G:A, 3'-G:T, 3'-T:T, 3'-A:G, 3'-G:G, 3'-A:C and 3'-C:C. Our findings indicate that Chlorella virus DNA ligase has the potential to affect genome integrity by embedding ribonucleotides in viral DNA and by sealing nicked molecules with mispaired ends, thereby generating missense mutations.
TL;DR: Self-inJurious behaviour is a prevalent and disabling disorder among adults with learning disabilities and the association of self-injurious behaviour with a wide range of other maladaptive behaviours was highly significant.
Abstract: BACKGROUND There have been few epidemiological studies of the disabling and poorly understood disorder self-injurious behaviour among adults with learning disabilities.
METHOD Interviews were undertaken with the carers of adults known to the Leicestershire Learning Disabilities Register (n = 2277). The Disability Assessment Schedule was used and information was also collected on demographic characteristics, developmental and physical status.
RESULTS Self-injurious behaviour was present in 17.4% of the population. In 1.7% self-injurious behaviour occurred frequently and was severe. There was no gender difference between those with and without self-injurious behaviour. Both the chronological age and developmental quotient of individuals with self-injurious behaviour were lower than those of individuals without self-injurious behaviour. Autistic symptoms were more common among those with self-injurious behaviour. The association of self-injurious behaviour with a wide range of other maladaptive behaviours was highly significant. Logistic regression analysis retained age, developmental quotient, hearing status, immobility and number of autistic symptoms as explanatory variables for self-injurious behaviour.
CONCLUSIONS Self-injurious behaviour is a prevalent and disabling disorder among adults with learning disabilities.
TL;DR: The STn(c) glycopeptide was modified by attachment of an MMCCH (4-N-maleimidomethyl) spacer arm to the aldehyde derivative, and then conjugated with thiolated KLH, which gave a higher epitope ratio and yield than the direct method.
Abstract: STn (NeuAcalpha2 --> 6GalNAc alpha-O-Ser/Thr) is a carbohydrate epitope overexpressed in various human carcinomas. Clinical trials are underway using synthetic STn or STn trimeric glycopeptides [STn, cluster; STn(c)] conjugated with keyhole limpet hemocyanin (KLH) as active specific immunotherapy for these cancers. These vaccines have been prepared by conjugating a crotyl ethyl amide derivative of STn or STn(c) to KLH by direct reductive amination after ozonolysis. In the case of STn(c) the conjugation efficiency and the resulting epitope ratios were low. This may be due to steric hinderance of the short spacer arm. To overcome these difficulties, without resynthesis, the STn(c) glycopeptide was modified by attachment of an MMCCH (4-(4-N-maieimidomethyl) cyclohexane-1-carboxyl hydrazide) spacer arm to the aldehyde derivative, and then conjugated with thiolated KLH. This method gave a higher epitope ratio and yield than the direct method. The STn(c)-MMCCH-KLH conjugate induced high titer antibodies in mice against STn(c). This method may be generally applicable for large synthetic oligosaccharides.
TL;DR: Mutational analysis establishes that conserved glutamate and arginine side chains within these motifs are essential for the RNA triphosphatase and ATPase activities of Cet1p in vitro and for Cet2p functionin vivo, suggesting that the metal-dependent RNA triPhosphatases encoded by yeast and DNA viruses comprise a novel family of phosphohydrolase enzymes with a common active site.
TL;DR: This article explored the impact of external structures on shopfloor control and the ways in which skilled dyers, and less skilled despatch workers, were able to shape the effort bargain and practise fiddles.
Abstract: Participant observation was undertaken at Button Co., a small manufacturing firm operating in the clothing sector. The paper explores the impact of external structures on shopfloor control and the ways in which skilled dyers, and less skilled despatch workers, were able to shape the effort bargain and practise fiddles. It shows a particular varient of small firm dynamics. Large retailers were important to the success of Button Co. but its broad customer base and niche market meant that it was not subject to a simple large/small firm dependency relationship. Control was fluid rather than imposed. Relations with large firms did impact upon the shopfloor, but not in a determinate way. Informal negotiation between directors and workers over throughput and quality occurred on a daily basis: as such, it provides some support to the view that the process of negotiating orders described by Ram (1994) is not ethnically specific.
TL;DR: The RNA triphosphatase and NTPase activities of baculovirus LEF-4 resemble those of the vaccinia virus and Saccharomyces cerevisiaemRNA capping enzymes, and it is suggested that these proteins comprise a novel family of metal-dependent triph phosphatases.
Abstract: Autographa californica nuclear polyhedrosis virus late and very late mRNAs are transcribed by an RNA polymerase consisting of four virus-encoded polypeptides: LEF-8, LEF-9, LEF-4, and p47. The 464-amino-acid LEF-4 subunit contains the signature motifs of GTP:RNA guanylyltransferases (capping enzymes). Here, we show that the purified recombinant LEF-4 protein catalyzes two reactions involved in RNA cap formation. LEF-4 is an RNA 5′-triphosphatase that hydrolyzes the γ phosphate of triphosphate-terminated RNA and a guanylyltransferase that reacts with GTP to form a covalent protein-guanylate adduct. The RNA triphosphatase activity depends absolutely on a divalent cation; the cofactor requirement is satisfied by either magnesium or manganese. LEF-4 also hydrolyzes ATP to ADP and Pi (Km = 43 μM ATP; Vmax = 30 s−1) and GTP to GDP and Pi. The LEF-4 nucleoside triphosphatase (NTPase) is activated by manganese or cobalt but not by magnesium. The RNA triphosphatase and NTPase activities of baculovirus LEF-4 resemble those of the vaccinia virus and Saccharomyces cerevisiae mRNA capping enzymes. We suggest that these proteins comprise a novel family of metal-dependent triphosphatases.
TL;DR: It is suggested that the Cet1-Ceg1 interaction is essential but not resolved whether the triphosphatase activity is also necessary, which highlights the potential for regulating mRNA cap formation through protein-protein interactions.
Abstract: vitro to form a Cet1-Ceg1 heterodimer. The interaction of Cet1 with Ceg1 elicits >10-fold stimulation of the guanylyltransferase activity of Ceg1. This stimulation is the result of increased affinity for the GTP substrate. A truncated protein, Cet1(201-549), has RNA triphosphatase activity, heterodimerizes with and stimulates Ceg1 in vitro, and suffices when expressed in single copy for cell growth in vivo. The more extensively truncated derivative Cet1(246-549) also has RNA triphosphatase activity but fails to stimulate Ceg1 in vitro and is lethal when expressed in single copy in vivo. These data suggest that the Cet1-Ceg1 interaction is essential but do not resolve whether the triphosphatase activity is also necessary. The mammalian capping enzyme Mce1 (a bifunctional triphosphatase-guanylyltransferase) substitutes for Cet1 in vivo. A mutation of the triphosphatase active-site cysteine of Mce1 is lethal. Hence, an RNA triphosphatase activity is essential for eukaryotic cell growth. This work highlights the potential for regulating mRNA cap formation through protein-protein interactions.
TL;DR: Limited evidence is provided that use of sunlamps increases the risk of melanoma, and the first use ofSunlamp before the age of 25 showed somewhat higher risk for melanoma compared to first use later in life.
Abstract: Results Of all study subjects, 141 (23%) cases and 95 (19%) controls reported ever having used sunlamps. The crude odds ratio (OR) for developing malignant melanoma after ever having used sunlamps was 1.30 (95% confidence interval [CI] : 0.971.74). This was reduced to 1.13 (95% CI : 0.82-1.54) after further adjusting for cutaneous phenotype and recreational sun exposure. Those who used more than one type of sunlamp had a threefold higher risk for melanoma compared to never users. Subgroup analyses showed that sunlamp use was associated with a greater increase in risk for melanoma among those who used sunlamps at home and those who were first exposed to sunlamps prior to 1971. The first use of sunlamps before the age of 25 showed somewhat higher risk for melanoma compared to first use later in life. Conclusion The current study provides limited evidence that use of sunlamps increases the risk of melanoma. For future studies, it is crucial that type of sunlamp, year of first use and amount of exposure are all taken into account. The association between melanoma and tanning with both UV-A and UV-B lamps and tanning under sunlamps early in life merits further investigation.
TL;DR: It is suggested that the formulation of cells detect extracellular signals by allostery and then give those signals meaning by 'regulated localization' applies to many biological processes and is particularly well illustrated by the mechanisms of gene regulation.
TL;DR: A stereoisomer of the natural product and not himastatin, an unusual dimeric depsipeptide with promising antibiotic and antitumor properties, was obtained from pyrroloindoline anti-cis-1 and this result led to a revision of the proposed stereostructure.
Abstract: A stereoisomer of the natural product and not himastatin, an unusual dimeric depsipeptide with promising antibiotic and antitumor properties, was obtained from pyrroloindoline anti-cis-1. This result led to a revision of the proposed stereostructure. The new stereostructure was confirmed by the total synthesis, which involves stereoselective access to the pyrroloindoline syn-cis-1 and the 5-hydroxypiperazic acid subunit and features a Stille coupling for the formation of the central carbon-carbon bond.