The Fa,b,c conjecture, I

In 1977 a five-part conjecture was made about a family of groups related to trivalent graphs and one part of the conjecture was proved. The conjecture completely determines all finite members of the family. Here we prove another part of the conjecture and foreshadow a paper which completes the proof of the other three parts.

The Fa,b,c conjecture is true, II

In 1977 a five-part conjecture was made about a family of groups related to trivalent graphs and subsequently two parts of the conjecture were proved. The conjecture completely determines all finite members of the family. Here we complete the proof of the conjecture by giving proofs for the remaining three parts. (c) 2006 Elsevier Inc. All rights reserved.

The effect of repeated prepulse and reflex stimulus presentations on startle prepulse inhibition

The magnitude of a startle reflex is inhibited if the reflex-eliciting stimuli is preceded by a prepulse stimulus at a short lead interval. Previous research in humans has shown that the extent of prepulse inhibition decreases over repeated presentations of reflex stimuli and prepulse-reflex stimulus pairings. The present study (N=70) investigated the effect of repeated presentations of prepulse stimuli, reflex stimuli, or prepulse-reflex stimulus pairings on prepulse inhibition. Five groups of subjects were presented during habituation training with either (a) reflex stimuli, (b) prepulse-reflex stimulus pairings, (c) a random sequence of prepulse and reflex stimuli, (d) prepulse stimuli, or (e) experimentally irrelevant light stimuli. Prepulse inhibition was reduced if startle stimuli were presented during habituation ((a), (b), (c)), but not after repeated presentation of the prepulse or the light stimulus ((d), (e)). The reduction in prepulse inhibition was abolished after dishabituation of the startle reflex. The present results indicate that habituation of the startle reflex can result in a reduction of prepulse inhibition. (C) 1998 Elsevier Science B.V.

Crystallization and preliminary X-ray diffraction studies of mammalian purple acid phosphatase

The oxidized form of purple acid phosphatase from pig allantoic fluid has been crystallized in the presence of phosphate using the hanging-drop technique. The crystals belong to the space group P2(1)2(1)2(1) and have unit-cell parameters a = 66.8, b = 70.3, c = 78.7 Angstrom. Diffraction data collected from a cryocooled crystal using a conventional X-ray source extend to 1.55 Angstrom resolution. A knowledge of the three-dimensional structure of mammalian purple acid phosphatase will aid in understanding the substrate specificity of the enzyme and will be important in the rational design of inhibitors, with potential in the treatment of bone diseases.

A role for protein kinase B beta/Akt2 in insulin-stimulated GLUT4 translocation in adipocytes

Insulin stimulates glucose uptake into muscle and fat cells by promoting the translocation of glucose transporter 4 (GLUT4) to the cell surface. Phosphatidylinositide 3-kinase (PI3K) has been implicated in this process. However, the involvement of protein kinase B (PKB)/Akt, a downstream target of PI3K in regulation of GLUT4 translocation, has been controversial. Here we report that microinjection of a PKB substrate peptide or an antibody to PKB inhibited insulin-stimulated GLUT4 translocation to the plasma membrane by 66 or 56%, respectively. We further examined the activation of PKB isoforms following treatment of cells with insulin or platelet-derived growth factor (PDGF) and found that PKB beta is preferentially expressed in both rat and 3T3-L1 adipocytes, whereas PKB alpha expression is down-regulated in 3T3-L1 adipocytes. A switch in growth factor response was also observed when 3T3-L1 fibroblasts were differentiated into adipocytes. While PDGF was more efficacious than insulin in stimulating PKB phosphorylation in fibroblasts, PDGF did not stimulate PKB beta phosphorylation to any significant extent in adipocytes, as assessed by several methods. Moreover, insulin, but not PDGF, stimulated the translocation of PKB beta to the plasma membrane and high-density microsome fractions of 3T3-L1 adipocytes. These results support a role for PKB beta in insulin-stimulated glucose transport in adipocytes.

PREDBALB/c: a system for the prediction of peptide binding to H2(d) molecules, a haplotype of the BALB/c mouse

PREDBALB/c is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. The predictions include the complete set of H2(d) class I ( H2-K-d, H2-L-d and H2-D-d) and class II (I-E-d and I-A(d)) molecules. The prediction system utilizes quantitative matrices, which were rigorously validated using experimentally determined binders and non-binders and also by in vivo studies using viral proteins. The prediction performance of PREDBALB/c is of very high accuracy. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PREDBALB/c is available at http://antigen.i2r.a-star.edu.sg/predBalbc/.

Crystal structure of P450cin in a complex with its substrate, 1,8-cineole, a close structural homologue to D-camphor, the substrate for P450cam

Cytochrome P450cin catalyzes the monooxygenation of 1,8-cineole, which is structurally very similar to D-camphor, the substrate for the most thoroughly investigated cytochrome P450, cytochrome P450cam. Both 1,8-cineole and D-camphor are C-10 monoterpenes containing a single oxygen atom with very similar molecular volumes. The cytochrome P450cin-substrate complex crystal structure has been solved to 1.7 Angstrom resolution and compared with that of cytochrome P450cam. Despite the similarity in substrates, the active site of cytochrome P450cin is substantially different from that of cytochrome P450cam in that the B' helix, essential for substrate binding in many cytochrome P450s including cytochrome P450cam, is replaced by an ordered loop that results in substantial changes in active site topography. In addition, cytochrome P450cin does not have the conserved threonine, Thr252 in cytochrome P450cam, which is generally considered as an integral part of the proton shuttle machinery required for oxygen activation. Instead, the analogous residue in cytochrome P450cin is Asn242, which provides the only direct protein H-bonding interaction with the substrate. Cytochrome P450cin uses a flavodoxin-like redox partner to reduce the heme iron rather than the more traditional ferredoxin-like Fe2S2 redox partner used by cytochrome P450cam and many other bacterial P450s. It thus might be expected that the redox partner docking site of cytochrome P450cin would resemble that of cytochrome P450BM3, which also uses a flavodoxin-like redox partner. Nevertheless, the putative docking site topography more closely resembles cytochrome P450cam than cytochrome P450BM3.

K-Ar and 40Ar/39Ar ages of dikes emplaced in the onshore basement of the Santos Basin, Resende area, SE Brazil: implications for the South Atlantic opening and tertiary reactivation

New K-Ar and Ar-40/Ar-39 data of tholeiitic and alkaline dike swarms from the onshore basement of the Santos Basin (SE Brazil) reveal Mesozoic and Tertiary magmatic pulses. The tholeiitic rocks (basalt, dolerite, and microgabbro) display high TiO2 contents (average 3.65 wt%) and comprise two magmatic groups. The NW-oriented samples of Group A have (La/Yb)N ratios between 15 and 32.3 and range in age from 192.9 +/- 2.2 to 160.9 +/- 1.9 Ma. The NNW-NNE Group B samples, with (La/Yb)(N) ratios between 7 and 16, range from 148.3 +/- 3 to 133.9 +/- 0.5 Ma. The alkaline rocks (syenite, trachyte, phonolite, alkaline basalts, and lamprophyre) display intermediate-K contents and comprise dikes, plugs, and stocks. Ages of approximately 82 Ma were obtained for the lamprophyre dikes, 70 Ma for the syenite plutons, and 64-59 Ma for felsic dikes. Because Jurassic-Early Cretaceous basic dikes have not been reported in SE Brazil, we might speculate that, during the emplacement of Group A dikes, extensional stresses were active in the region before the opening of the south Atlantic Ocean and coeval with the Karoo magmatism described in South Africa. Group B dikes yield ages compatible with those obtained for Serra Geral and Ponta Grossa magmatism in the Parana Basin and are directly related to the breakup of western Gondwana. Alkaline magmatism is associated with several tectonic episodes that postdate the opening of the Atlantic Ocean and related to the upwelling of the Trindade plume and the generation of Tertiary basins southeast of Brazil. In the studied region, alkaline magmatism can be subdivided in two episodes: the first one represented by lamprophyre dykes of approximately 82 Ma and the second comprised of felsic alkaline stocks of approximately 70 Ma and associated dikes ranging from 64 to 59 Ma. (c) 2005 Elsevier Ltd. All rights reserved.

Duration of cannabis use - a novel phenotype?

Although cannabis is the most commonly used illicit drug, duration of cannabis use is typically short, with many of those who initiate cannabis use ceasing use by their late twenties. In this paper we analyze data from a volunteer Australian cohort of 6265 male and female twins to examine whether the duration of cannabis use is an informative phenotype for future genetic analyses. Genetic modeling indicated: (a) moderate genetic influences on duration of cannabis use in both males (41%; 95% CI = 31–51) and females (55%; 95% CI = 46–63); (b) strong genetic influences on cannabis dependence in both males (72%, 95% CI = 61–81) and females (62%, 95% CI = 48–74); (c) no evidence of shared environmental influences on duration of cannabis use or on cannabis dependence in either males or females. Importantly, this model fitting indicated that a substantial component of genetic influences (rg = .90, 95% CI = .77–.99 (males); .70, 95% CI = .57–.83 (females)) on duration of cannabis use was shared with those influencing liability to cannabis dependence. While there were high genetic correlations in both women and men, lifetime duration of cannabis may be uniquely informative in assessing components of liability to cannabis use.

Phenolic compounds in tea from Australian supermarkets

Phenolic compounds constitute 50-70% of tea water extract and are the main quality parameters for teas. Theaflavins (TF), thearubigins (TR) and theabrownins (TB) are the major polyphenols that determine the quality of black tea. These compounds were measured in 56 leaf teas and teabags sampled from Australian supermarkets in Queensland. The various quantities of TF, ranging from 0.29% to 1.25%, indicate a quality difference that exists among the teas studied. Low TF content in black tea may be due to over-fermenting and/or long periods of storage. The solubility of TR and TB from teabags ranged from 82% to 92%, indicating that the permeability of teabags was variable. Variable quantities of TF in Australian teas show instability and a tendency of TF to oxidize during storage. Total polyphenols in green teas ranged from 14% to 34%, indicating a large variation, which was not reflected in price. The solubility of total polyphenols from teabags has been proposed as a useful quality index of the filtering paper used for the teabags. This chemical analysis of phenolic compounds in commercial teas may be a potential tool for the quality control of Australian manufactured and imported teas in Australian markets. (C) 2005 Elsevier Ltd. All rights reserved.

SCOTROC 2A: Carboplatin followed by docetaxel or docetaxel gemcitabine as first-line chemotherapy for ovarian cancer

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P = 0.102, P = 0.056, P = 0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% Cl: 10.5 - 20.6); arm B 18.1 months (95% Cl: 15.9 - 20.3); arm C, 13.7 months (95% Cl: 12.8 - 14.6). Neutropenia was the predominant grade 3 - 4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P = 0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.