The Aurora A and B kinases are up-regulated in bone marrow-derived chronic lymphocytic leukemia cells and represent potential therapeutic targets

Background The malignant B cells in chronic lymphocytic leukemia receive signals from the bone marrow and lymph node microenvironments which regulate their survival and proliferation. Characterization of these signals and the pathways that propagate them to the interior of the cell is important for the identification of novel potential targets for therapeutic intervention. Design and Methods We compared the gene expression profiles of chronic lymphocytic leukemia B cells purified from bone marrow and peripheral blood to identify genes that are induced by the bone marrow microenvironment. Two of the differentially expressed genes were further studied in cell culture experiments and in an animal model to determine whether they could represent appropriate therapeutic targets in chronic lymphocytic leukemia. Results Functional classification analysis revealed that the majority of differentially expressed genes belong to gene ontology categories related to cell cycle and mitosis. Significantly up-regulated genes in bone marrow-derived tumor cells included important cell cycle regulators, such as Aurora A and B, survivin and CDK6. Down-regulation of Aurora A and B by RNA interference inhibited proliferation of chronic lymphocytic leukemia-derived cell lines and induced low levels of apoptosis. A similar effect was observed with the Aurora kinase inhibitor VX-680 in primary chronic lymphocytic leukemia cells that were induced to proliferate by CpG-oligonucleotides and interleukin-2. Moreover, VX-680 significantly blocked leukemia growth in a mouse model of chronic lymphocytic leukemia. Conclusions Aurora A and B are up-regulated in proliferating chronic lymphocytic leukemia cells and represent potential therapeutic targets in this disease.

Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. Trichodesmium sp nov.

Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micro-molar concentrations (1, IC50 4.0 mu M; 2, IC50 3.8 mu M).

Brazilian avian metapneumovirus subtypes A and B: experimental infection of broilers and evaluation of vaccine efficacy

Santos M.B., Martini M.C., Ferreira H.L., Silva L.H.A., Fellipe P.A., Spilki F.R. & Arns C.W. 2012. Brazilian avian metapneumovirus subtypes A and B: experimental infection of broilers and evaluation of vaccine efficacy. Pesquisa Veterinaria Brasileira 32(12):1257-1262. Laboratorio de Virologia, Instituto de Biologia, Universidade Estadual de Campinas, Rua Monteiro Lobato s/n, Cx. Postal 6109, Campinas, SP 13083-970, Brazil. E-mail: arns@unicamp.br Avian metapneumovirus (aMPV) is a respiratory pathogen associated with the swollen head syndrome (SHS) in chickens. In Brazil, live aMPV vaccines are currently used, but subtypes A and, mainly subtype B (aMPV/A and aMPV/B) are still circulating. This study was conducted to characterize two Brazilian aMPV isolates (A and B subtypes) of chicken origin. A challenge trial to explore the replication ability of the Brazilian subtypes A and B in chickens was performed. Subsequently, virological protection provided from an aMPV/B vaccine against the same isolates was analyzed. Upon challenge experiment, it was shown by virus isolation and real time PCR that aMPV/B could be detected longer and in higher amounts than aMPV/A. For the protection study, 18 one-day-old chicks were vaccinated and challenged at 21 days of age. Using virus isolation and real time PCR, no aMPV/A was detected in the vaccinated chickens, whereas one vaccinated chicken challenged with the aMPV/B isolate was positive. The results showed that aMPV/B vaccine provided a complete heterologous virological protection, although homologous protection was not complete in one chicken. Although only one aMPV/B positive chicken was detected after homologous vaccination, replication in vaccinated animals might allow the emergence of escape mutants.

Classifying A-field and B-field configurations in the presence of D-branes. Part II: Stacks of D-branes

In the paper of Bonora et al. (2008) [3] we have shown, in the context of type II superstring theory, the classification of the allowed B-field and A-field configurations in the presence of anomaly-free D-branes, the mathematical framework being provided by the geometry of gerbes. Here we complete the discussion considering in detail the case of a stack of D-branes, carrying a non-abelian gauge theory, which was just sketched in Bonora et al. (2008) [3]. In this case we have to mix the geometry of abelian gerbes, describing the B-field, with the one of higher-rank bundles, ordinary or twisted. We describe in detail the various cases that arise according to such a classification, as we did for a single D-brane, showing under which hypotheses the A-field turns out to be a connection on a canonical gauge bundle. We also generalize to the non-abelian setting the discussion about "gauge bundles with non-integral Chern classes", relating them to twisted bundles with connection. Finally, we analyze the geometrical nature of the Wilson loop for each kind of gauge theory on a D-brane or stack of D-branes.

PBL and B-Learning for Civil Engineering Students in a Transportation Course

The results of a pedagogical strategy implemented at the University of Sao Paulo at Sao Carlos are presented and discussed. The initiative was conducted in a transportation course offered to Civil Engineering students. The approach is a combination of problem-based learning and project-based learning (PBL) and blended-learning (B-learning). Starting in 2006, a different problem was introduced every year. From 2009 on, however, the problem-based learning concept was expanded to project-based learning. The performance of the students was analyzed using the following elements: (1) grades in course activities; (2) answers from a questionnaire designed for course evaluation; and (3) cognitive maps made to assess the effects of PBL through the comparison of the responses provided by the students involved and those not involved in the experiment. The results showed positive aspects of the method, such as a strong involvement of several students with the subject. A gradual increase in the average scores obtained by the students in the project activities (from 6.77 in 2006 to 8.24 in 2009) was concomitant with a better evaluation of these activities and of the course as a whole (90 and 97% of options "Good" or "Very good" in 2009, respectively). A growing interest in the field of transportation engineering as an alternative for further studies was also noticed. DOI: 10.1061/(ASCE)EI.1943-5541.0000115. (C) 2012 American Society of Civil Engineers.

Role of Coulomb and nuclear breakups in the interaction of B-8 with C-12

We investigate the breakup of the proton halo B-8 projectile in the presence of the light target C-12 at near barrier energies. Our calculations show that the effect of the breakup on the elastic scattering angular distributions is negligible. We also investigate the relative importance of Coulomb and nuclear breakups for this system. We compare the results of our calculations with those for the He-6 + C-12 and B-8 Ni-58 systems. (C) 2012 Elsevier B.V. All rights reserved.

Biochemical characterization and comparative analysis of two distinct serine proteases from Bothrops pirajai snake venom

This study reports the isolation and biochemical characterization of two different serine proteases from Bothrops pirajai snake venom, thus providing a comparative analysis of the enzymes. The isolation process consisted of three consecutive chromatographic steps (Sephacryl S-200, Benzamidine Sepharose and C2/C18), resulting in two serine proteases, named BpirSP27 and BpirSP41 after their molecular masses by mass spectrometry (27,121 and 40,639 Da, respectively). Estimation by SDS-PAGE under denaturing conditions showed that, when deglycosylated with PNGase F, BpirSP27 and BpirSP41 had their molecular masses reduced by approximately 15 and 42%, respectively. Both are acidic enzymes, with pI of approximately 4.7 for BpirSP27 and 3.7 for BpirSP41, and their N-terminal amino acid sequences showed 57% identity to each other, with high similarity to the sequences of other snake venom serine proteases (SVSPs). The enzymes showed different actions on bovine fibrinogen, with BpirSP27 acting preferentially on the B beta chain and BpirSP41 on both A alpha and B beta chains. The two serine proteases were also able to degrade fibrin and blood clots in vitro depending on the doses and incubation periods, with higher results for BpirSP41. Both enzymes coagulated the human plasma in a dose-dependent manner, and BpirSP41 showed a higher coagulant potential, with minimum coagulant dose (MCD) of similar to 3.5 mu g versus 20 mu g for BpirSP27. The enzymes were capable of hydrolyzing different chromogenic substrates, including S-2238 for thrombin-like enzymes, but only BpirSP27 acted on the substrate S-2251 for plasmin. They also showed high stability against variations of temperature and pH, but their activities were significantly reduced after preincubation with Cu2+ ion and specific serine protease inhibitors. In addition. BpirSP27 induced aggregation of washed platelets to a greater extent than BpirSP41. The results showed significant structural and functional differences between B. pirajai serine proteases, providing interesting insights into the structure-function relationship of SVSPs. (C) 2012 Elsevier Masson SAS. All rights reserved.