Peculiar Velocity Reconstruction with Fast Action Method: Tests on Mock Redshift Surveys

We present extensive tests of the Fast Action Method (FAM) for recovering the past orbits of mass tracers in an expanding universe from their redshift-space coordinates at the present epoch. The tests focus on the reconstruction of present-day peculiar velocities using mock catalogs extracted from high resolution $N$-body simulations. The method allows for a self-consistent treatment of redshift-space distortions by direct minimization of a modified action for a cosmological gravitating system. When applied to ideal, volume limited catalogs, FAM recovers unbiased peculiar velocities with a 1-D, 1\sigma error of ~220 km/s, if velocities are smoothed on a scale of 5 Mpc/h. Alternatively, when no smoothing is applied, FAM predicts nearly unbiased velocities for objects residing outside the highest density regions. In this second case the 1\sigma$error decreases to a level of ~150 km/s. The correlation properties of the peculiar velocity fields are also correctly recovered on scales larger than 5 Mpc/h. Similar results are obtained when FAM is applied to flux limited catalogs mimicking the IRAS PSCz survey. In this case FAM reconstructs peculiar velocities with similar intrinsic random errors, while velocity-velocity correlation properties are well reproduced beyond scales of ~8 Mpc/h. We also show that FAM provides better velocity predictions than other, competing methods based on linear theory or Zel'dovich approximation. These results indicate that FAM can be successfully applied to presently available galaxy redshift surveys such as IRAS PSCz.Comment: 26 pages, 16 figures. Figures 1,2,3,4,5,7,11,12 and 16 are also included as separate gif files. Added 2 new sections(5.3 and 6.3) and figures (11 and 16). More discussion added to section 7 (Summary and Conclusions). MNRAS accepte

Muscarinic Regulation of Ca2+ Currents in Rat Sensory Neurons: Channel and Receptor Types, Dose ‐ response Relationships and Cross‐talk Pathways

We studied, in rat sensory neurons, the modulation of high voltage‐activated Ca2+ currents (ICa mediated by the pertussis toxin‐sensitive activation of muscarinic receptors, which were found to be of subtypes M2, or M4. Muscarine reversibly blocked somatic Ca2+ spikes but strong predepolarizations only partially relieved the inhibited Ca2+ current. On the other hand, the putative coupling messenger could not rapidly diffuse towards channels whose activity was recorded from a macro‐patch. The perforated patch technique virtually prevented the response rundown present during whole‐cell experiments. Both ω‐conotoxin GVIA (ω‐CgTx)‐sensitive channels and ω‐CgTx‐ and dihydropyridine‐resistant channels are coupled to the muscarinic receptor, but not the L‐channel. When measured in the same neuron, dose ‐ response relationships for the first and subsequent agonist applications differed; maximal inhibition, the reciprocal of half‐maximal concentration and the Hill coefficient were always highest in the first trial. Muscarine and oxotremorine exhibited monotone dose ‐ response curves, but oxotremorine‐M showed non‐linear relationships which became monotonic when cells were intracellularly perfused with inhibitors of protein kinase A (PKA) and C (PKC), suggesting that either PKA or receptor‐induced PKC could phosphorylate and thus inactivate G‐proteins or other unknown proteins involved in inhibitory muscarinic actions on ICa. In summary, these data provide a preliminary pharmacological characterization of the muscarinic inhibition of the Ca2+ channels in sensory neurons, with implications about agonist specificity and the interplay between signalling pathways

Maize polyamine oxidase in the presence of spermine/spermidine induces the apoptosis of LoVo human colon adenocarcinoma cells

Amine oxidases, which contribute to the regulation of polyamine levels, catalyze the oxidative deamination of polyamines to generate H 2 O 2 and aldehyde(s). In this study, and at least to the best of our knowledge, maize polyamine oxidase (ZmPAO) was used for the first time with the aim of identifying a novel strategy for cancer therapy. The cytotoxicity and the mechanisms of cell death induced by the enzymatic oxidation products of polyamine generated by ZmPAO were investigated. Exogenous spermine and ZmPAO treatment decreased cell viability in a spermine dose- and time-dependent manner, particularly, the viability of the multidrug-resistant (MDR) colon adenocarcinoma cells, LoVo DX, when compared with drug-sensitive ones (LoVo WT). Further analyses revealed that H 2 O 2 derived from spermine was mainly responsible for the cytotoxicity. Flow cytometric analysis revealed that treatment with ZmPAO and spermine increased the apoptotic population of LoVo WT and LoVo DX cells. In addition, we found that treatment with ZmPAO and spermine markedly reduced mitochondrial membrane potential in the LoVo DX cells, in agreement with the results of cell viability and apoptosis assays. Transmission electron microscopic observations supported the involvement of mitochondrial depolarization in the apoptotic process. Therefore, the dysregulation of polyamine metabolism in tumor cells may be a potential therapeutic target. In addition, the development of MDR tumor cells is recognized as a major obstacle in cancer therapy. Therefore, the design of a novel therapeutic strategy based on the use of this combination may be taken into account, making this approach attractive mainly in treating MDR cancer patients