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Diaz, F.

Publications and source records attributed to Diaz, F..

21 records · Page 2Linked to original sources

Two antagonistic microtubule targeting drugs act synergistically to kill cancer cells

Paclitaxel is a microtubule stabilizing agent and a successful drug for cancer chemotherapy inducing, however, adverse effects. To reduce the effective dose of paclitaxel, we searched for drugs which could potentiate its therapeutic effect. We have screened a chemical library and selected Carba1, a carbazolone, which exerts synergistic cytotoxic effects on tumor cells grown in vitro, when co-administrated with a low dose of paclitaxel. Carba1 targets the colchicine binding-site of tubulin and is a microtubule-destabilizing agent. The Carba1-induced modulation of microtubule dynamics increases the accumulation of fluorescent paclitaxel inside microtubules, providing a mechanistic explanation of the observed synergy between Carba1 and paclitaxel. The synergistic effect of Carba1 with paclitaxel on tumor cell viability was also observed in vivo in xenografted mice. Thus, a new mechanism favoring paclitaxel accumulation in microtubules can be transposed to in vivo mouse cancer treatments, paving the way for new therapeutic strategies combining low doses of microtubule targeting agents with opposite mechanisms of action.

cancer biology↗

Multiple QTL mapping in autopolyploids: a random-effect model approach with application in a hexaploid sweetpotato full-sib population

In developing countries, the sweetpotato, Ipomoea batatas (L.) Lam. (2n = 6x = 90), is an important autopolyploid species, both socially and economically. However, quantitative trait loci (QTL) mapping has remained limited due to its genetic complexity. Current fixed-effect models can only fit a single QTL and are generally hard to interpret. Here we report the use of a random-effect model approach to map multiple QTL based on score statistics in a sweetpotato bi-parental population ( Beauregard x Tanzania) with 315 full-sibs. Phenotypic data were collected for eight yield component traits in six environments in Peru, and jointly predicted means were obtained using mixed-effect models. An integrated linkage map consisting of 30,684 markers distributed along 15 linkage groups (LGs) was used to obtain the genotype conditional probabilities of putative QTL at every cM position. Multiple interval mapping was performed using our R package QTLPOLY and detected a total of 41 QTL, ranging from one to ten QTL per trait. Some regions, such as those on LGs 3 and 15, were consistently detected among root number and yield traits and provided basis for candidate gene search. In addition, some QTL were found to affect commercial and noncommercial root traits distinctly. Further best linear unbiased predictions allowed us to characterize additive allele effects as well as to compute QTL-based breeding values for selection. Together with quantitative genotyping and its appropriate usage in linkage analyses, this QTL mapping methodology will facilitate the use of genomic tools in sweetpotato breeding as well as in other autopolyploids.

genetics↗

Effects of chronic thermal stress on the reproductive performance of male Octopus maya

In female Octopus maya the reproductive success has well-defined thermal limits; beyond which, spawning, number of eggs, fecundity, and the viability of the embryos are reduced. Observations of wild male O. maya suggest that temperatures below 27{degrees}C favour their reproductive performance. From these observations we hypothesize that, as in females, the temperature modulates the reproductive performance of adult O. maya males. The study was directed to evaluate the physiological condition, reproductive success, and histological damage in testis of male O. maya exposed to thermal stress, to determine the implications of ocean warming over their reproductive performance. High temperatures (28-30{degrees}C) negatively affect the growth and health of male O. maya. In octopuses maintained at 30{degrees}C, as a consequence of the thermal stress we observed an increment in the haemocytes number, a reduction in the oxygen consumption rate, and an inflammatory process in the testis. The number of spermatozoa per spermatophore was not affected by temperature, but higher spermatophores production was observed at 30{degrees}C. The paternity analysis showed that the offspring had multiple paternity with an average of 10 males contributing in a single spawn. The paternal contribution was affected by temperature with high, medium, or no paternal contribution in animals maintained at 24{degrees}C (control group), 28{degrees}C, and 30{degrees}C, respectively. The temperatures from 28{degrees}C to 30{degrees}C deeply affected the reproductive performance of Octopus maya males.

ecology↗