Structural and functional properties of Bp-LAAO, a new L-amino acid oxidase isolated from Bothrops pauloensis snake venom

An L-amino acid oxidase (Bp-LAAO) from Bothrops pauloensis snake venom was highly purified using sequential chromatography steps on CM-Sepharose, Phenyl-Sepharose CL4B, Benzamidine Sepharose and C18 reverse-phase HPLC. Purified Bp-LAAO showed to be a homodimeric acidic glycoprotein with molecular weight around 65 kDa under reducing conditions in SDS-PAGE. The best substrates for Bp-LAAO were L-Met, L-Leu, L-Phe and L-Ile and the enzyme showed a strong reduction of its catalytic activity upon L-Met and L-Phe substrates at extreme temperatures. Bp-LAAO showed leishmanicidal, antitumoral and bactericidal activities dose dependently. Bp-LAAO induced platelet aggregation in platelet-rich plasma and this activity was inhibited by catalase. Bp-LAAC-cDNA of 1548 bp codified a mature protein with 516 amino acid residues corresponding to a theoretical isoelectric point and molecular weight of 6.3 and 58 kDa, respectively. Additionally, structural and phylogenetic studies identified residues under positive selection and their probable location in Elp-LAAO and other snake venom LAAOs (svLAAOs). Structural and functional investigations of these enzymes can contribute to the advancement of toxinology and to the elaboration of novel therapeutic agents. (C) 2009 Elsevier Masson SAS. All rights reserved.

A new thrombospondin-related anonymous protein homologue in Neospora caninum (NcMIC2-like1)

Neospora caninum is an Apicomplexan protozoan that has the dog as a definitive host and cattle (among other animals) as intermediate hosts. It causes encephalopathy in dogs and abortion in cows, with significant loss in worldwide livestock. As any Apicomplexan, the parasite invades the cells using proteins contained in the phylum-specific organelles, like the micronemes, rhoptries and dense granules. The aim of this study was the characterization of a homologue (denominated NcMIC2-like1) of N. caninum thrombospondin-related anonymous protein (NcMIC2), a micronemal protein previously shown to be involved in the attachment and connection with the intracellular motor responsible for the active process of invasion. A polyclonal antiserum raised against the recombinant NcMIC2-like1 functional core (thrombospondin and integrin domains) recognized the native form of NcMIC2-like1, inhibited the in vitro invasion process and localized NcMIC2-like1 at the apical complex of the parasite by confocal immunofluorescence, indicating its micronemal localization. The new molecule, NcMIC2-like1, has features that differentiates it from NcMIC2 in a substantial way to be considered a homologue dagger.

Influence of Plasma Protein Binding on Pharmacodynamics: Estimation of In Vivo Receptor Affinities of beta Blockers Using a New Mechanism-Based PK-PD Modelling Approach

The objective of this investigation was to examine in a systematic manner the influence of plasma protein binding on in vivo pharmacodynamics. Comparative pharmacokinetic-pharmacodynamic studies with four beta blockers were performed in conscious rats, using heart rate under isoprenaline-induced tachycardia as a pharmacodynamic endpoint. A recently proposed mechanism-based agonist-antagonist interaction model was used to obtain in vivo estimates of receptor affinities (K(B),(vivo)). These values were compared with in vitro affinities (K(B),(vitro)) on the basis of both total and free drug concentrations. For the total drug concentrations, the K(B),(vivo) estimates were 26, 13, 6.5 and 0.89 nM for S(-)-atenolol, S(-)-propranolol, S(-)-metoprolol and timolol. The K(B),(vivo) estimates on the basis of the free concentrations were 25, 2.0, 5.2 and 0.56 nM, respectively. The K(B),(vivo)-K(B),(vitro) correlation for total drug concentrations clearly deviated from the line of identity, especially for the most highly bound drug S(-)-propranolol (ratio K(B),(vivo)/K(B),(vitro) similar to 6.8). For the free drug, the correlation approximated the line of identity. Using this model, for beta-blockers the free plasma concentration appears to be the best predictor of in vivo pharmacodynamics. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3816-3828, 2009

Intellectuals in a Network A New Generation Faces the Challenges of Development

Brazilian social thought draws on the inspiration of past masters the common denominator of whose work is probably a deep humanism. Confronting the challenges of a fluid, ever-changing reality is now a matter of survival. The idea of climate change has made the environment, long relegated to second place, a matter of much wider interest and concern. The other great problem is poverty, and here, while there have been undeniable advances, much remains to be done. The main challenge is producing forms of social organization that will allow ordinary citizens to have an impact on what really matters. Developing policy in these areas has engaged the efforts of a wide range of experts from a variety of fields. Whereas university-educated intellectuals once formed an intelligentsia, today they are engaged in practical politics and much more often function as agents who link social actors together than as mere elaborators of theories.

Modal functions of future tenses in French

The paper disputes two influential claims in the Romance Linguistics literature. The first is that the synthetic future tenses in spoken Western Romance are now rivalled, if not supplanted, as temporal functors by the more recently developed GO futures. The second is that these synthetic futures now have modal rather than temporal meanings in spoken Romance. These claims are seen as reflecting a universal cycle of diachronic change, in which verb forms originally expressing modal (or aspectual) values take on future temporal reference, becoming tenses. The new modal meanings supplant the temporal, which are then taken up by new forms. Challenges to this theory for French are raised on the basis of empirical evidence of two sorts. Positively, future tenses in spoken Romance continue to be used with temporal meaning. Negatively, evidence of modal meaning for these forms is lacking. The evidence comes froma corpora of spoken French, native speaker judgements and verb data from a daily broadsheet. Cumulatively, it points to the reverse of the claims noted above: the synthetic future in spoken French has temporal but little modal meaning.

H56 Standard House for PNG Housing Commission, Papua New Guinea

As seen from street.

Three-bedroom townhouses, Air Niugini Staff Housing, Papua New Guinea

Street elevation, carports below entry balconies.

Two-bedroom townhouses, Air Niugini Staff Housing, Papua New Guinea

As seen from road.

Three-bedroom townhouse, Air Niugini Staff Housing, Papua New Guinea

Side elevation, showing upper level bedroom windows.

The predicate marker li in Mauritian Creole

There is a morpheme 'li' in Mauritian Creole (MC), which is homophonous with the 3sg pronoun, and which, in the early creole, occurs frequently between the subject and the predicate in affirmative, present tense clauses. I propose that that 'li' may have originated as a resumptive pronoun, co-referential with the subject, but following the grammaticalization of new determiner elements to mark the semantic contrasts of [±definite] and singular vs. plural, 'li' has now grammaticalized into a predicate marker. Its presence is sensitive to both the nature of the predicate, and to the definiteness and specificity features of the subject NP. My analysis is within the framework of Truth Conditional Semantics, where indefinite NPs are analyzed as variables that get introduced into the discourse, and must be bound by an operator to yield a closed proposition, with a truth value. Drawing on a comparison with a cognative morpheme 'i' in Seychellois Creole, I claim that its path to grammaticalization is linked to that of the specificity marking 'la'.

Pedagogical work and the 'cult of the body': Considering the role of HPE in the context of the 'new public health'

Physical education, now often explicitly identified with health in contemporary school curricula, continues to be implicated in the (re)production of the 'cult of the body'. We argue that HPE is a form of health promotion that attempts to 'make' healthy citizens of young people in the context of the 'risk society'. In our view there is still work to be done in understanding how and why physical education (as HPE) continues to be implicated in the reproduction of values associated with the cult of body. We are keen to understand why HPE continues to be ineffective in helping young people gain some measure of analytic and embodied 'distance' from the problematic aspects of the cult of the body. This paper offers an analysis of this enduring issue by using some contemporary analytic discourses including 'governmentality', 'risk society' and the 'new public health'.

Evidence of a spotted fever-like rickettsia and a potential new vector from northeastern Australia

A spotted fever-like rickettsia was identified in a Hemaphysalis tick by polymerase chain reaction (PCR) amplification and sequencing of the 16S rDNA, ompA, and ompB genes. A comparison of these nucleotide sequences with those of other spotted fever group (SFG) rickettsiae revealed that the Hemaphysalis tick rickettsia was distinct from other previously reported strains. Phylogenetic analysis based on both ompA and ompB also indicates that the strain’s closest relatives are the agents of Thai tick typhus (Rickettsia honei strain TT-118) and Flinders Island spotted fever (R. honei). This study represents the first report of an R. honei-like agent from a Hemaphysalis tick in Australia and of a spotted fever group rickettsia from Cape York Peninsula, Queensland.