AMG-232, a New Inhibitor of MDM-2, Enhance Doxorubicin Efficiency in Pre-B Acute Lymphoblastic Leukemia Cells

Background:Doxorubicin (DOX)-induced cardiotoxicity appears to be a growing concern for extensive use in acute lymphoblastic leukemia (ALL). The new combination treatment strategies, therefore might be an effective way of decreasing its side effects as well as improving efficacy. AMG232 (KRT-232) is a potential MDM-2 inhibitor, increasing available p53 through disturbing p53-MDM-2 interaction. In this study, we examined the effects of AMG232 on DOX-induced apoptosis of NALM-6 cells.Methods:The anti-leukemic effects of Doxorubicin on NALM-6 cells, either alone or in combination with AMG232, were confirmed by MTT assay, Annexin/PI apoptosis assay, and cell cycle analysis. Expression of apoptosis and autophagy-related genes were further evaluated by Real time-PCR method. To investigate the effect of AMG232 on NALM-6 cells, the activation of p53, p21, MDM-2, cleaved Caspase-3 proteins was evaluated using western blot analysis.Results:The results showed that AMG232 inhibition of MDM-2 enhances Doxorubicin-induced apoptosis in NALM-6 cells through caspase-3 activation in a time and dose-dependent manner. Furthermore, co-treatment of AMG232 with Doxorubicin hampered the transition of NALM-6 cells from G1 phase through increasing p21 protein. In addition, this combination treatment led to enhanced expression of apoptosis and autophagy-related genes in ALL cell lines.Conclusion:The results declared that AMG232 as an MDM-2 inhibitor could be an effective approach to enhance antitumor effects of Doxorubicin on NALM-6 cells as well as an effective future treatment for ALL patients.Key Words: Acute Lymphoblastic Leukemia, AMG 232, Autophagy, Doxorubicin, p53     

Summer distribution of Red-legged Partridges Alectoris rufa in relation to water availability on Mediterranean farmland

The suggestion that the summer distribution of Red-legged Partridges Alectoris rufa in the Mediterranean region is determined by the availability of surface water was examined on the agricultural farm, Alto Alentejo, southern Portugal. Partridge coveys were surveyed between 15 July and 15 August in 1993 and 1994. Using a vector-based Geographic Information System, we assessed, for each covey location and for the locations of a double number of random points, the distance to the nearest water point, distance to field boundaries, distance to water lines and land use classes. Univariate comparisons were made between the two groups of locations, and three multivariate logistic models were fitted through forward stepwise selection to the 1993, 1994 and pooled data sets to estimate the probability of sighting partridge coveys in the study area. Distance to water was significantly lower for partridge locations than for random points in both years and was the only variable selected for all logistic models. Apart from water availability, Red-legged Partridge locations were also affected by land use and distance to field boundaries.     

Zea ribosomal repeat evolution and substitution patterns

Zea and Tripsacum nuclear ribosomal internal transcribed spacer (ITS) sequences were used to evaluate patterns of concerted evolution, rates of substitutions, patterns of methylation-induced deamination, and structural constraints of the ITS. ITS pseudogenes were identified by their phylogenetic position, differences in nucleotide composition, extensive deamination at ancestral methylation sites, and substitutions resulting in low-stability secondary RNA structures. Selection was important in shaping the kinds of polymorphisms and substitutions observed in the ITS. ITS substitution rates were significantly different among the Zea taxa. Deamination of cytosines at methylation sites was a potent mutation source, but selection appeared to maintain high methylation site density throughout the ribosomal repeat except for the gene promoter. Nucleotide divergence statistics identified selectively constrained regions at the 5' ends of the ITS1 and ITS2.      

Concerted transpositions of mobile genetic elements coupled with fitness changes in Drosophila melanogaster

In an inbred low-activity (LA) strain of Drosophila melanogaster with a low level of fitness and a complex of inadaptive characters, in situ hybridization reveals an invariant pattern of distribution of three copia-like elements (mdg-1, mdg-3, and copia). Rare, spontaneous, multiple transpositions of mobile elements in the LA strain were shown to be coupled with a drastic increase of fitness. A changed pattern of various types of mobile elements was also observed on selecting the LA strain for higher fitness. High-fitness strains show transpositions of mobile elements to definite chromosomal sites ("hot spots"). Concerted changes in the location of three different mobile elements were found to be coupled with an increase of fitness. The mdg-1 distribution patterns were also examined in two low-fitness strains independently selected from the high-fitness ones. Fitness decrease was accompanied by mdg-1 excision from the hot spots of their location usually detected in the high-fitness strains. The results suggest the existence of a system of adaptive transpositions of mobile elements that takes part in fitness control.      

Use of Camera-Trapping to Estimate Puma Density and Influencing Factors in Central Brazil

Abstract: We used remotely triggered cameras to collect data on Puma (Puma concolor) abundance and occupancy in an area of tropical forest in Brazil where the species' status is poorly known. To evaluate factors influencing puma occupancy we used data from 5 sampling campaigns in 3 consecutive years (2005 to 2007) and 2 seasons (wet and dry), at a state park and a private forest reserve. We estimated puma numbers and density for the 2007 sampling data by developing a standardized individual identification method. We based individual identification on 1) time-stable parameters (SP; physical features that do not change over time), and 2) time-variable parameters (VP; marks that could change over time such as scars and botfly marks). Following individual identification we established a capture-recapture history and analyzed it using closed population capture-mark-recapture models. Puma capture probability was influenced by camera placement (roads vs. trails), sampling year, and prey richness. Puma occupancy was positively associated with species richness and there was a correlation between relative puma and jaguar (Panthera onca) abundance. Identifications enabled us to generate 8 VP histories for each photographed flank, corresponding to 8 individuals. We estimated the sampled population at 9 pumas (SE = 1.03, 95% CI = 8–10 individuals) translating to a density of 3.40 pumas/100 km². Information collected using camera-traps can effectively be used to assess puma population size in tropical forests. As habitat progressively disappears and South American felines become more vulnerable, our results support the critical importance of private forest reserves for conservation.