A Comparative Study of In Vitro Cytotoxic,Antioxidant, and Antimicrobial Activity of Pt(II), Zn(II), Cu(II), and Co(III) Complexes with N‐heteroaromatic Schiff Base (E)‐2‐[N′‐(1‐pyridin‐2‐yl‐ethylidene)hydrazino]acetate

In search for novel biologically active metal based compounds, an evaluation of in vitro cytotoxic, antioxidant, and antimicrobial activity of new Pt(II) complex and its Zn(II), Cu(II), and Co(III) analogues, with NNO tridentately coordinated N‐heteroaromatic Schiff base ligand (E)‐2‐[N′‐(1‐pyridin‐2‐yl‐ethylidene)hydrazino]acetate, was performed. Investigation of antioxidative properties showed that all of the compounds have strong radical scavenging potencies. The Zn(II) complex showed potent inhibition of DNA cleavage by hydroxyl radical. A cytotoxic action of investigated compounds was evaluated on cultures of human promyelocitic leukaemia (HL‐60), human glioma (U251), rat glioma (C6), and mouse melanoma (B16) cell lines. It was shown that binuclear pentacoordinated Zn(II) complex possesses a strong dose‐dependent cytotoxic activity, of the same order of magnitude as cisplatin on B16, C6, and U251 cells. Furthermore, Zn(II) complex causes oxidative stress‐induced apoptotic death of HL‐60 leukemic cells, associated with caspase activation, phosphatidylserine externalization, and DNA fragmentation.     

A pairwise relatedness estimator for polyploids

Studies in genetics and ecology often require estimates of relatedness coefficients based on genetic marker data. Many diploid estimators have been developed using either method‐of‐moments or maximum‐likelihood estimates. However, there are no relatedness estimators for polyploids. The development of a moment estimator for polyploids with polysomic inheritance, which simultaneously incorporates the two‐gene relatedness coefficient and various ‘higher‐order’ coefficients, is described here. The performance of the estimator is compared to other estimators under a variety of conditions. When using a small number of loci, the estimator is biased because of an increase in ill‐conditioned matrices. However, the estimator becomes asymptotically unbiased with large numbers of loci. The ambiguity of polyploid heterozygotes (when balanced heterozygotes cannot be distinguished from unbalanced heterozygotes) is also considered; as with low numbers of loci, genotype ambiguity leads to bias. A software, PolyRelatedness , implementing this method and supporting a maximum ploidy of 8 is provided.     

Haplotype Analysis of the Human Endogenous Retrovirus Locus HERV-K(HML-2.HOM) and Its Evolutionary Implications

We and others recently identified an almost-intact human endogenous retrovirus (HERV), termed HERV-K(HML-2.HOM), that is usually organized as a tandem provirus. Studies on HERV proviral loci commonly rely on the analysis of single alleles being taken as representative for a locus. We investigated the frequency of HERV-K(HML-2.HOM) single and tandem alleles in various human populations. Our analysis revealed that another HERV-K(HML-2) locus, the so-called HERV-K(II) provirus, is also present as a tandem provirus allele in the human population. Proviral tandem formations were identified in various nonhuman primate species. We furthermore examined single nucleotide polymorphisms (SNPs) within the HERV-K(HML-2.HOM) proviral gag, prt, and pol genes, which all result in nonsense mutations. We identified four proviral haplotypes displaying different combinations of gag, prt, and pol SNPs. Haplotypes harboring completely intact proviral genes were not found. For the left provirus of the tandem arrangement a haplotype displaying intact gag and prt genes and a mutated pol was found in about two-thirds of individuals from different ethnogeographic origins. The same haplotype was always found in the right provirus. The various haplotypes point toward multiple recombination events between HERV-K(HML-2.HOM) proviruses. Based on these findings we derive a model for the evolution of the proviral locus since germ line integration. [Reviewing Editor : Dr. Martin Kreitman]     

Coa3 and Cox14 are essential for negative feedback regulation of COX1 translation in mitochondria

Regulation of eukaryotic cytochrome oxidase assembly occurs at the level of Cox1 translation, its central mitochondria-encoded subunit. Translation of COX1 messenger RNA is coupled to complex assembly in a negative feedback loop: the translational activator Mss51 is thought to be sequestered to assembly intermediates, rendering it incompetent to promote translation. In this study, we identify Coa3 (cytochrome oxidase assembly factor 3; Yjl062w-A), a novel regulator of mitochondrial COX1 translation and cytochrome oxidase assembly. We show that Coa3 and Cox14 form assembly intermediates with newly synthesized Cox1 and are required for Mss51 association with these complexes. Mss51 exists in equilibrium between a latent, translational resting, and a committed, translation-effective, state that are represented as distinct complexes. Coa3 and Cox14 promote formation of the latent state and thus down-regulate COX1 expression. Consequently, lack of Coa3 or Cox14 function traps Mss51 in the committed state and promotes Cox1 synthesis. Our data indicate that Coa1 binding to sequestered Mss51 in complex with Cox14, Coa3, and Cox1 is essential for full inactivation.     

The failure of global migration governance

The deconstruction of the moral polity around forced migration proposed by Thomas Faist in his article “The moral polity of forced migration” can, in some ways, be interpreted as an analysis of the failure of global migration governance. In this comment, I review the challenges faced by those claiming their human rights, suggesting – in addition to Faist’s explanations – some further causes of and consequences for the current situation. I then explore the type of claim made by refugees in their protests, using the concept of weak agency, which relativizes the statement made by Faist that their claim is not subversive.     

Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents

Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target, since inhibitors of this protease affect the pathology appropriately. By exploring the N-acylhydrazones (NAH) as privileged structures usually present in antiparasitic agents, we investigated a library of 16 NAH bearing the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold (NAH 3a–h, 4a–h). The in vitro bioactivity against epimastigote and trypomastigote forms of T. cruzi was evaluated, and some NAH under study exhibited antitrypanosomal activity at concentrations that are not toxic to mammalian cells. The series of compounds based on the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold revealed the remarkable importance of each substituent at the phenyl’s 4-position for the inhibitory activity. Non-nitrated compounds 3a and 4e were found to be as potent as the reference drug, Benznidazole. In addition, the molecular origin of the antitrypanosomal properties for these series was investigated using docking studies of the TCC structure.     

Mapping and expression studies of the mir17-92 cluster on pig Chromosome 11

We have identified the first porcine microRNA (miRNA) cluster (the mir17-92 cluster) and localized it to the q-arm of pig Chromosome 11. The miRNA cluster was found by sequence similarity search with human miRNA sequences against the pig genomic data generated within the Sino-Danish pig genome project. The resulting data contained three complete and two incomplete miRNA precursors of seven miRNAs from the human mir17-92 cluster. Because there is a 100% sequence identity between the four pig miRNAs and the corresponding human miRNAs, the sequences of three unavailable pig miRNAs were derived from the human data. The expression profiles of seven studied miRNAs were analyzed by hybridization to Northern blots containing five porcine tissues: cerebellum, cortex, hippocampus, kidney, and liver. In order to determine the localization of the mir17-92 cluster in the pig genome, we mapped it by PCR in the porcine somatic cell hybrid (SCH) panel and in the INRA-University of Minnesota (INRA-UMN) porcine radiation hybrid (IMpRH) panel. The PCR results enabled us to localize this cluster to the q-arm of pig Chromosome 11 and map it in relation to two microsatellites. Our study presents the first expression analyses of miRNAs in pig and adds information for further functional studies in this species.     

Overexpression of the rice Osmyb4 gene increases chilling and freezing tolerance of Arabidopsis thaliana plants

The expression of the gene Osmyb4, detected at low level in rice (Oryza sativa) coleoptiles grown for 3 days at 29 degrees C, is strongly induced by treatments at 4 degrees C. At sublethal temperatures of 10 and 15 degrees C, its expression in rice seedlings is already evident, but this effect cannot be vicariated by other stresses or ABA treatment. We demonstrate by transient expression that Myb4 transactivates the PAL2, ScD9 SAD and COR15a cold-inducible promoters. The Osmyb4 function in vivo is demonstrated overexpressing its cDNA in Arabidopsis thaliana plants (ecotype Wassilewskija) under the control of the constitutive CaMV 35S promoter. Myb4 overexpressing plants show a significant increased cold and freezing tolerance, measured as membrane or Photosystem II (PSII) stability and as whole plant tolerance. Finally, in Osmyb4 transgenic plants, the expression of genes participating in different cold-induced pathways is affected, suggesting that Myb4 represents a master switch in cold tolerance.     

Combined effects of shade and drought on tulip poplar seedlings: trade‐off in tolerance or facilitation?

It has been hypothesised that many natural plant distribution patterns can be explained by a trade-off between shade and drought tolerance which would make plants more sensitive to shade under dry conditions. On the other hand, shading by nurse plants is often observed to enhance growth and survival of smaller plants in dry areas. This paper describes an experiment designed to address the interactive effects of drought and shade on growth and physiology of tulip poplar seedlings ( Liriodendron tulipifera ) grown in shade houses under different combinations of irradiance (1%, 5%, 12%, 17%, and 27% of ambient PAR) and soil water content (5–9%, 11–15%, and>20%). The results show no evidence that higher PAR levels compensate for the negative effects of drought on photosynthesis and growth. Rather, rates of estimated daily shoot carbon gain decreased with PAR under dry conditions. Daily xylem sapflow patterns indicated that this was associated with a strong reduction in stomatal conductance in plants growing in dry soil and high PAR conditions. Whole-shoot light compensation points were higher for plants raised under higher PAR conditions, but were not significantly influenced by the water treatments. Shoot dark respiration rates decreased under drier conditions. These results do not support the hypothesis of a trade-off between shade and drought tolerance. Instead, they indicate mechanisms that can lead to positive effects of shading by neighbouring plants under dry conditions. Indeed, such facilitation is thought to be important in many plant communities.