A comprehensive phylogeny of extinct and extant Rhizomyinae (Rodentia): evidence for multiple intercontinental dispersals

The subfamily Rhizomyinae is known from the Late Oligocene up to the present. Today this group comprises six species, which live in southern Asia and eastern Africa. Despite the current moderate diversity of the rhizomyines, they had a greater diversification and wider distribution in the past: from Asia, their land of origin, to Africa, which they entered during the Early Miocene. So far 33 fossil species can be referred to this group. A cladistic analysis involving fossil and living species has been carried out. Prokanisamys spp. turned out to be the most basal taxa of the ingroup. This analysis calls into question the monophyly of several genera, and allows the proposal of a phylogenetic definition of the tribes Tachyoryctini and Rhizomyini. It also provides information about the origin of the African rhizomyines and allows inferring multiple dispersal phenomena from Asia to Africa in Early and Late Miocene times.     

Modelling the protective efficacy of alternative delivery schedules for intermittent preventive treatment of malaria in infants and children

Background

Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is recommended by WHO where malaria incidence in infancy is high and SP resistance is low. The current delivery strategy is via routine Expanded Program on Immunisation contacts during infancy (EPI-IPTi). However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy.

Methods and Findings

A mathematical model was developed to estimate the protective efficacy (PE) of IPT against clinical malaria in children aged 2-24 months, using entomological and epidemiological data from an EPI-IPTi trial in Navrongo, Ghana to parameterise the model. The protection achieved by seasonally-targeted IPT in infants (sIPTi), seasonal IPT in children (sIPTc), and by case-management with long-acting artemisinin combination therapies (LA-ACTs) was predicted for Navrongo and for sites with different transmission intensity and seasonality. In Navrongo, the predicted PE of sIPTi was 26% by 24 months of age, compared to 16% with EPI-IPTi. sIPTc given to all children under 2 years would provide PE of 52% by 24 months of age. Seasonally-targeted IPT retained its advantages in a range of transmission patterns. Under certain circumstances, LA-ACTs for case-management may provide similar protection to EPI-IPTi. However, EPI-IPTi or sIPT combined with LA-ACTs would be substantially more protective than either strategy used alone.

Conclusion

Delivery of IPT to infants via the EPI is sub-optimal because individuals are not protected by IPT at the time of highest malaria risk, and because older children are not protected. Alternative delivery strategies to the EPI are needed where transmission varies seasonally or the malaria burden extends beyond infancy. Long-acting ACTs may also make important reductions in malaria incidence. However, delivery systems must be developed to ensure that both forms of chemoprevention reach the individuals who are most exposed to malaria.     

Sensitization of taxol-induced apoptosis by curcumin involves down-regulation of nuclear factor-kappaB and the serine/threonine kinase Akt and is independent of tubulin polymerization

Taxol is the best anticancer agent that has ever been isolated from plants, but its major disadvantage is its dose-limiting toxicity. In this study, we report with mechanism-based evidence that curcumin, a nontoxic food additive commonly used by the Indian population, sensitizes tumor cells more efficiently to the therapeutic effect of Taxol. A combination of 5 nm Taxol with 5 microm curcumin augments anticancer effects more efficiently than Taxol alone as evidenced by increased cytotoxicity and reduced DNA synthesis in HeLa cells. Furthermore, our results reveal that this combination at the cellular level augments activation of caspases and cytochrome c release. This synergistic effect was not observed in normal cervical cells, 293 cells (in which Taxol down-regulates nuclear factor-kappaB (NF-kappaB)), or HeLa cells transfected with inhibitor kappaBalpha double mutant (IkappaBalpha DM), although the transfection itself sensitized the cells to Taxol-induced cytotoxicity. Evaluation of signaling pathways common to Taxol and curcumin reveals that this synergism was in part related to down-regulation of NF-kappaB and serine/threonine kinase Akt pathways by curcumin. An electrophoretic mobility shift assay revealed that activation of NF-kappaB induced by Taxol is down-regulated by curcumin. We also noted that curcumin-down-regulated Taxol induced phosphorylation of the serine/threonine kinase Akt, a survival signal which in many instances is regulated by NF-kappaB. Interestingly, tubulin polymerization and cyclin-dependent kinase Cdc2 activation induced by Taxol was not affected by curcumin. Altogether, our observations indicate that Taxol in combination with curcumin may provide a superior therapeutic index and advantage in the clinic for the treatment of refractory tumors.     

Differential activation of Smads in HeLa and SiHa cells that differ in their response to transforming growth factor-beta

We assessed the responsiveness of six human cervical cancer cell lines to transforming growth factor (TGF)-beta with p3TP-lux reporter assay and found that HeLa and SiHa cells were highly responsive to TGF-beta. However, when pSBE4-BV/Luc reporter with four Smad binding elements was used, only the SiHa, not the HeLa, cells showed Smad activation. Smad DNA binding activity was relatively more in SiHa than in HeLa cells upon TGF-beta treatment, and the active complex contained Smad 2 and Smad 4. In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, HeLa cells treated with 5 ng/ml of TGF-beta for 24 h showed proliferation, whereas SiHa cells showed growth inhibition under the same conditions. TGF-beta treatment resulted in G(0)/G(1) arrest with a reduction in S-phase only in SiHa cells. A chemical inhibitor of Smad activation (SB203580) blocked the growth inhibitory effect of TGF-beta in SiHa, whereas the proliferative response in HeLa was unaffected. TGF-beta-induced translocation of phospho-Smad 2 was relatively less in HeLa than in SiHa cells. MAPK activation occurred within 5 min and persisted up to 15 min upon TGF-beta treatment in HeLa but was negligible in SiHa cells. TGF-beta activated JNK in HeLa, but SiHa cells showed a down-regulation of its activity. When an inhibitor of MAPK (U0126) was used, the TGF-beta-mediated proliferative response in HeLa cells was completely abolished. SB203580 did not affect MAPK activation induced by TGF-beta in HeLa cells. We report for the first time an activation, presumably independent of Smad activation, of TGF-beta-dependent MAPK within 5 min of treatment that resulted in cell cycle progression in a cervical adenocarcinoma cell line, HeLa.     

The effects of climate change on the phenology of selected Estonian plant, bird and fish populations

This paper summarises the trends of 943 phenological time-series of plants, fishes and birds gathered from 1948 to 1999 in Estonia. More than 80% of the studied phenological phases have advanced during springtime, whereas changes are smaller during summer and autumn. Significant values of plant and bird phases have advanced 5–20 days, and fish phases have advanced 10–30 days in the spring period. Estonia’s average air temperature has become significantly warmer in spring, while at the same time a slight decrease in air temperature has been detected in autumn. The growing season has become significantly longer in the maritime climate area of Western Estonia. The investigated phenological and climate trends are related primarily to changes in the North Atlantic Oscillation Index (NAOI) during the winter months. Although the impact of the winter NAOI on the phases decreases towards summer, the trends of the investigated phases remain high. The trends of phenophases at the end of spring and the beginning of summer may be caused by the temperature inertia of the changing winter, changes in the radiation balance or the direct consequences of human impacts such as land use, heat islands or air pollution.     

Pollination biology and breeding system in five nocturnal species of <Emphasis Type="Italic">Oenothera</Emphasis> (Onagraceae): reproductive assurance and opportunities for outcrossing

The capacity to produce seed, both by selfing and outcrossing, or mixed mating strategies, is considered a mechanism for overcoming unpredictable pollinator availability. In the present study, we investigate breeding system, insect visitations and the role of insect visitors in the pollination of five species of Oenothera subsect. Oenothera. Field experiments showed that autonomous selfing occurs at bud stage, prior to the opening of the flower. Control flowers showed similar seed set to hand-pollinated flowers, whereas emasculated flowers and those subject to open pollination set fewer seed. These results are consistent with the hypothesis that the investigated Oenothera exhibit a great capacity for autonomous selfing and that selfing is selected in order to provide reproductive assurance. Although flowers were visited mostly by nocturnal lepidopterans, these insects did not precipitate pollination and are thus considered nectar thieves. Conversely, analysis of pollen loads and behavior during foraging by diurnal insect visitors revealed that honeybees and bumblebees are the probable pollinators. We conclude that production of flowers capable of autonomous selfing at bud stage, followed by anthesis and opportunities for outcrossing, probably improves the invasive potential of these Oenothera in Europe, together with a rapid increase in their populations, even when pollinators are scarce.