Search

Male harm arises when traits that increase reproductive success in competition with other males also harm females as a side effect. The extent of harm depends on male and female phenotypes, both of which can diverge between populations. Within a population, harm is inferred when increased exposure to males reduces female fitness, but studies of the divergence of male harm rarely manipulate male exposure. Here, we quantify male harm and compare its magnitude between two lab populations of Drosophila serrata that were derived from a common ancestor 7 years earlier and subsequently held under conditions that minimized environmental differences. We manipulated female exposure to males in a factorial design involving all four combinations of males and females from these populations, providing insight into divergence in both sexes. Our results reveal substantial harm to females and provide stronger evidence of divergence in males than in females. Using these and other published data, we discuss conceptual issues surrounding the quantification and comparison of harm that arise because it involves a comparison of multiple quantities (e.g., female fitness under varying male exposure), and we demonstrate the increased insight that is gained by manipulating male exposure to quantify these quantities.

Sable Island, Nova Scotia, Canada hosts one of few natural populations of feral horses (Equus caballus) never exposed to anthelmintics. Coproculture revealed cyathostomes, Strongylus equinus, S. edentatus, and S. vulgaris, with S. equinus (unusually) dominating in adult horses and cyathostomes dominating in young horses (, Graphical abstract Image 1, Highlights • Horses of Sable island have a unique parasite fauna never exposed to anthelmintics. • Sable horses tolerate strongyle fecal egg counts much higher than domestic equids. • Unusually, adult Sable horses have patent ascarid and lungworm infections. • This work has conservation and biosecurity implications for Sable horses. • This work provides insights into responsible parasite management in domestic horses.

Inter-individual variation in juvenile body size can have important consequences for individual fitness, population dynamics, and adaptive evolution. In wild vertebrate populations, larger juvenile size is usually expected to be selected for. However, understanding how such selection may translate into adaptive evolution requires an understanding of the genetic underpinnings of early development and the factors modulating selection. In this study, we characterised the genetic basis of and selection pressures acting upon juvenile body size in a large insular population of feral horses on Sable Island, Canada, to gain insights into the evolution of juvenile body size in wild vertebrate populations. We used pedigree-based quantitative genetic ‘animal models’ to quantify the sources of phenotypic variation in withers-knee length, and assessed the influence of maternal age, sex, and temporal (birth year) and spatial environmental heterogeneity in modulating overwinter survival selection. We found that withers-knee length is moderately heritable and that there was a significant positive genetic correlation between males and females. There was no indication of directional selection in a pooled-sex analysis, but we did find evidence for significant sexually antagonistic selection, with a tendency for smaller body size to be favoured in males and larger body size to be favoured in females. These results suggest that juvenile body size has the potential to evolve in this population, and that selection on juvenile size may play an important role in modulating sex-specific contributions to population dynamics. However, our results also suggest that there is unlikely to be evolutionary change in the mean body size of Sable Island foals.

Three strained Ru(II) metal-organic dyads were prepared and characterized by NMR, mass spectrometry, and analytical HPLC to probe whether these constructs could act as multifunctional photochemotherapy (PCT) agents. The compounds incorporated the crowded 6,6'-dimethyl-2,2'-bipyridine (6,6'-dmb) ligand to impart stoichiometric photocisplatin activity, and imidazo[4,5-f] [1,10]phenanthroline (IP) appended with n thiophene units (nT; n=1-3) to add capacity for singlet oxygen sensitization. With visible light activation, each complex of the series underwent rapid and selective photoejection of 6,6'-dmb in less than 10min, with half-lives (t1/2) as short as 46.3s for [Ru(6,6'-dmb)2(IP-1T)](2+). Photo-triggered ligand loss slowed with increasing n, and was slowest for [Ru(6,6'-dmb)2(IP-3T)](2+) (t1/2=273s). This trend also held for photoadduct formation with DNA; [Ru(6,6'-dmb)2(IP-1T)](2+) produced relaxed circular DNA at the lowest concentrations. Singlet oxygen yields (ΦΔ) increased with n, whereby ΦΔ for [Ru(6,6'-dmb)2(IP-1T)](2+) was only 3%, but increased to 42% on going to [Ru(6,6'-dmb)2(IP-3T)](2+). This photosensitization process was reflected by single-strand breaks in the gel-mobility shift assays of [Ru(6,6'-dmb)2(IP-3T)](2+), but was not discernible for the other compounds. Despite different photochemical and photophysical reactivities, all of the compounds were potent phototoxic agents toward cancer cells (EC50=1-2μM) with relatively short compound-to-light intervals and moderate visible light doses. [Ru(6,6'-dmb)2(IP-3T)](2+) was exceptionally photoactive toward cancer cells at longer intervals (EC50=200nM, PI=750). Phototherapeutic margins increased with n due to decreased dark cytotoxicity for the more π-expansive complexes, making metal-organic dyad [Ru(6,6'-dmb)2(IP-3T)](2+) the best multifunctional PCT agent.

Ru(II) dyads derived from organic units that impart low-lying 3IL excited states combine the most attractive features of organic photosensitizers with those of coordination complexes. The result is a bichromophoric system with excited-state lifetimes that are significantly longer than those associated with traditional 3MLCT states. Incorporation of α-oligothiophenes as the organic chromophore leads to systems that act as dual Type I/II photosensitizers, opening up the possibility of treating hypoxic tumors with photodynamic therapy (PDT) and overcoming problems with in vivo dosimetry. These photosensitizers, particularly those that consist of three thiophene units and higher, are remarkable DNA binders and photocleavers when exposed to light, exhibiting no interference with DNA structural integrity in the absence of a light-trigger. Such light-responsive agents localize in the nuclei of cells without the need for a carrier and produce a potent PDT response with minimal dark toxicity. This phototherapeutic effect translates directly to animals and is superior to the clinical agent Photofrin® in this model. These Ru(II) dyads can be activated with light in the PDT window, despite very low molar extinction coefficients in this region, and this phenomenon can be attributed to the efficiency with which these agents operate. The ability to activate these prodrugs with ultraviolet to near-infrared light marks an unprecedented versatility that can be exploited to match treatment depth to tumor invasion depth without compromising potency, giving rise to photosensitizers for multiwavelength PDT.

There is a general expectation that sexual selection should align with natural selection to aid the purging of deleterious mutations, yet experiments comparing purging under monogamy versus polygamy have provided mixed results. Recent studies suggest that this may be because the simplified mating environments used in these studies reduce the benefit of sexual selection through males and hamper natural selection through females by increasing costs associated with sexual conflict. To test the effect of the physical mating environment on purging, we use experimental evolution inDrosophila melanogasterto track the frequency of four separate deleterious mutations in replicate populations that experience polygamy under either a simple or structurally complex mating arena while controlling for arena size. Consistent with past results suggesting a greater net benefit of polygamy in a complex environment, two of the mutations were purged significantly faster in this environment. The other two mutations showed no significant difference between environments.

Prodigiosenes, possessing a 4-methoxypyrrolyldipyrrin skeleton, are known for their anti-cancer activity. Structural modification of the C-ring resulted in a series of prodigiosenes that displayed promising activity against leukemia cell lines during in vitro analysis against the NCI 60 cancer cell line panel. Further in vivo studies of these compounds using the zebrafish model showed persistence of anti-leukemia properties in human K562 chronic myelogenous leukemia cells.

Analogues of the tripyrrolic natural product prodigiosin bearing an additional methyl and a carbonyl group at the C-ring were synthesised and evaluated. In vitro anticancer activity screening (NCI) and the study of modes of action (copper-mediated cleavage of double-stranded DNA and transmembrane transport of chloride anions) showed that the presence of the methyl group is not detrimental to activity. Furthermore, although the presence of an ester conjugated to the prodigiosene C-ring seems to decrease both pKa and chloride transport efficiency compared to the natural product, these analogues still exhibit a high rate of chloride transport. All analogues exhibit good in vitro anticancer activity and reduced toxicity compared to the natural product: compare an acute systemic toxicity of 100 mg kg−1 in mice vs. 4 mg kg−1 for prodigiosin, pointing towards a larger therapeutic window than for the natural product.

Analogues of the tripyrrolic natural product prodigiosin bearing an additional methyl and a carbonyl group at the C-ring were synthesised and evaluated. In vitro anticancer activity screening (NCI) and the study of modes of action (copper-mediated cleavage of double-stranded DNA and transmembrane transport of chloride anions) showed that the presence of the methyl group is not detrimental to activity. Furthermore, although the presence of an ester conjugated to the prodigiosene C-ring seems to decrease both pK(a) and chloride transport efficiency compared to the natural product, these analogues still exhibit a high rate of chloride transport. All analogues exhibit good in vitro anticancer activity and reduced toxicity compared to the natural product: compare an acute systemic toxicity of 100 mg kg(-1) in mice vs. 4 mg kg(-1) for prodigiosin, pointing towards a larger therapeutic window than for the natural product.