Proapoptotic activity in vitro of two novel ruthenium(II) complexes with flavanone-based ligands that overcome cisplatin resistance in human bladder carcinoma cells

In this study we examined their proapoptotic activity of cis-dichloridobis(3-imino-2-methoxyflavanone)ruthenium(II)3H₂O (1) and cis-dichloridobis(3-imino-2-ethoxyflavanone)ruthenium(II)2H₂O (2) towards human bladder carcinoma cell line EJ and its cisplatin resistant subline EJcisR. On the basis of the experiments we carried out, it may be concluded, that: CDDP (cis-diamminedichloridoplatinum) resistance of EJcisR cells is probably based on partial loss of apoptotic pathway activating caspase-8 and increased resistance to DNA strand breaks and/or alkali-labile sites. Increased glutathione levels, as well as activity of P-gp transporter seems to be not relevant in this case. The proapoptotic activity of the ruthenium compounds is higher than that of cisplatin. Higher proapoptotic activity of 1 and 2 when compared to CDDP may be due to the presence of large, lipophilic flavanone-based ligands that may facilitate their trans-membrane transport and their redox activity. 1 and 2 induce apoptosis apparently in more than one way. Although caspase-8 activation and DNA strand breaks and/or alkali-labile sites are caused by the compounds, their ability to cause the oxidative stress in the cells may also participate in apoptosis induction.     

Unusual anchor of a motor complex (MyoD-MLC2) to the plasma membrane of Toxoplasma gondii

Toxoplasma gondii possesses 11 rather atypical myosin heavy chains. The only myosin light chain described to date is MLC1, associated with myosin A, and contributing to gliding motility. In this study, we examined the repertoire of calmodulin-like proteins in Apicomplexans, identified six putative myosin light chains and determined their subcellular localization in T. gondii and Plasmodium falciparum. MLC2, only found in coccidians, is associated with myosin D via its calmodulin (CaM)-like domain and anchored to the plasma membrane of T. gondii via its N-terminal extension. Molecular modeling suggests that the MyoD-MLC2 complex is more compact than the reported structure of Plasmodium MyoA-myosin A tail-interacting protein (MTIP) complex. Anchorage of this MLC2 to the plasma membrane is likely governed by palmitoylation.     

Resisting resistance

This month's Genome Watch describes how knowledge of the malaria parasite genome can be used to better understand and mitigate the emergence of drug resistance.     

Skull shape variation in extant and extinct Testudinata and its relation to habitat and feeding ecology

Turtles (Testudinata) are a diverse group of reptiles that conquered a broad set of habitats and feeding ecologies over the course of their well‐documented evolutionary history. We here investigate the cranial shape of 171 representatives of the turtle lineage and the relationship of shape to different habitat and diet preferences using two‐dimensional geometric morphometrics. The skull shape of extant turtles correlates with both ecological proxies, but is more affected by habitat than diet. However, the application of these correlations to extinct turtles produces mostly flawed results, as least when compared to external data such as sedimentary environment, highlighting that the morphospace held by extant turtles is not necessarily the optimal location in tree space for a particular ecology. The inability of this study to correctly predict the ecology of extinct turtles is likely related to the fact that the shape of turtle skulls is dominated by the emarginations and jaw closure mechanisms, two shape features unrelated to habitat or feeding ecology. This indicates that various specializations that are apparent in the skull only contribute little to overall shape.     

Genotoxicity of novel trans-platinum(II) complex with diethyl (pyridin-4-ylmethyl)phosphate in human non-small cell lung cancer cells A549

The dynamic development of metal-containing anticancer drugs has started since the discovery of cis-diamminedichloroplatinum(II). For many years it was believed that trans platinum(II) compounds were non-active as antitumour agents because trans-diamminedichloroplatinum is biologically inactive although it binds to DNA and also forms monoadducts and cross-links. In the present work the ability of a novel platinum(II) compound trans-[PtCl(2)(4-pmOpe)(2)] to induce DNA damage in human non-small cell lung cancer cells A549 was examined using the alkaline comet assay. The obtained results revealed that the novel trans platinum(II) complex induced DNA strand breaks, which were effectively repaired during 2h of post-incubation, and cross-links which remained unrepaired under these test conditions. Apart from that, the modified comet assay with incubation with proteinase K was used to verify the ability of trans-[PtCl(2)(4-pmOpe)(2)] and cis-DDP to form DNA-protein cross-links. It has been proved that only trans-[PtCl(2)(4-pmOpe)(2)] complex exhibits the ability to induce DNA-protein cross-links. The results suggest a different mechanism of action of this compound in comparison to cis-DDP. It seems that trans geometry and the presence of two diethyl (pyridin-4-ylmethyl)phosphates as non-leaving ligands can determine dissimilar properties of the adducts formed on DNA and the different mechanism of action of trans-[PtCl(2)(4-pmOpe)(2)] and in consequence the efficacy in killing cancer cells.     

Acorn and aquatic invertebrate biomass in Mississippi Alluvial Valley hardwood bottomlands

The Mississippi Alluvial Valley (MAV) is an internationally important migration and wintering region for Nearctic waterfowl. Most of the MAV is a lowland forested floodplain that contains vast stands of red oaks (Quercus spp.). These trees produce acorns and, when forests flood, diverse communities of aquatic invertebrates emerge, providing diverse nutritious foods for wintering ducks. The MAV is within the Lower Mississippi Valley Joint Venture (LMV JV) region of the North American Waterfowl Management Plan, but no combined MAV-wide estimates of acorn and invertebrate biomass exist to determine foraging carrying capacity for conservation planning or actions by the LMV JV or other partners in regions containing southern red oaks. We sampled acorns that fell to the ground or were submersed under shallow water deemed accessible to foraging ducks and aquatic invertebrates in the MAV of Louisiana, Mississippi, Missouri, and Tennessee, USA, during fall-winter 2009–2011. In good and poor masting years, acorn abundance was non-linearly related to the percentage of the forest canopy made up of red oaks and peaked in late autumn or winter when most other waterfowl resources are depleted or decomposed. This finding is novel and represents a deviation from how the LMV JV has traditionally assumed food resources exist for waterfowl in hardwood bottomlands. We used a daily ration model to estimate energy use days (EUDs) from combined acorn and invertebrate biomasses relative to red oak canopy coverage. For good and poor acorn masting years at the mean MAV-wide red oak canopy coverage of 45%, EUD = 2,273.1 days/ha and 161.2 days/ha, respectively. The LMV JV currently uses EUD = 385–502 days/ha for forests with 40–50% red oak canopy coverage. Because acorns and aquatic macro-invertebrates are a food resource that persists through winter and reaches peak abundance later in winter, we contend conservation planners have undervalued the potential of bottomland hardwoods to provide energy for wintering ducks.     

On the identification of feather structures in stem-line representatives of birds: evidence from fossils and actuopalaeontology

Dinosaurs with fossilized filamentous integument structures are usually preserved in a highly flattened state. Several different feather types have been described on this basis, but the two-dimensional preservation of specimens during fossilization makes the identification of single feather structures difficult due to overlapping feather structures in vivo. Morphological comparison with the diversity of recent feather types is therefore absolutely vital to avoid misinterpretation. To simulate the preservation process, a cadaver of recent Carduelis spinus (European siskin) was flattened in a printing press. Afterwards, the structure of the plumage was compared with the morphology of a single body feather from the same specimen. In comparison with the single feather, the body plumage of the flattened bird looked rather filamentous. It was almost impossible to identify single structures, and in their place, various artefacts were produced. The investigation of plumage in a specimen of the Mesozoic bird Confuciusornis sanctus reveals similar structures. This indicates that flattening of specimens during fossilization amplifies the effect of overlapping among feathers and also causes a loss of morphological detail which can lead to misinterpretations. The results are discussed in connection with some dubious feather morphologies in recently described theropods and basal birds. Based on recent feather morphology, the structure of so-called proximal ribbon-like pennaceous feathers (PRPFs) found in many basal birds is reinterpreted. Furthermore, the morphology of a very similar-looking feather type found in the forelimb and tail of an early juvenile oviraptorosaur is discussed and diagnosed as the first feather generation growing out of the feather sheath. Thus, the whole plumage of this theropod might represent neoptile plumage.