Exploring the role of fallopian ciliated cells in the pathogenesis of high-grade serous ovarian cancer

High-grade serous epithelial ovarian cancer (HGSOC) is the fifth leading cause of cancer death in women and the first among gynecological malignancies. Despite an initial response to standard chemotherapy, most HGSOC patients relapse. To improve treatment options, we must continue investigating tumor biology. Tumor characteristics (e.g., risk factors and epidemiology) are valuable clues to accomplish this task. The two most frequent risk factors for HGSOC are the lifetime number of ovulations, which is associated with increased oxidative stress in the pelvic area caused by ovulation fluid, and a positive family history due to genetic factors. In the attempt to identify novel genetic factors (i.e., genes) associated with HGSOC, we observed that several genes in linkage with HGSOC are expressed in the ciliated cells of the fallopian tube. This finding made us hypothesize that ciliated cells, despite not being the cell of origin for HGSOC, may take part in HGSOC tumor initiation. Specifically, malfunction of the ciliary beat impairs the laminar fluid flow above the fallopian tube epithelia, thus likely reducing the clearance of oxidative stress caused by follicular fluid. Herein, we review the up-to-date findings dealing with HGSOC predisposition with the hypothesis that fallopian ciliated cells take part in HGSOC onset. Finally, we review the up-to-date literature concerning genes that are located in genomic loci associated with epithelial ovarian cancer (EOC) predisposition that are expressed by the fallopian ciliated cells

Maternal longevity and offspring sex in wild ungulates

In species with sexual size dimorphism, the offspring of the larger sex usually have greater energy requirements and may lead to greater fitness costs for parents. The effects of offspring sex on maternal longevity, however, have only been tested in humans. Human studies produced mixed results and considerable debate mainly owing to the difficulty of distinguishing the effects of sexual dimorphism from sociocultural factors. To advance this debate, we examined how the relative number of sons influenced maternal longevity in four species of free-living ungulates (Soay sheep Ovis aries ; bighorn sheep, Ovis canadensis ; red deer, Cervus elaphus ; mountain goat, Oreamnos americanus ), with high male-biased sexual size dimorphism but without complicating sociocultural variables. We found no evidence for a higher cumulative cost of sons than of daughters on maternal longevity. For a given number of offspring, most females with many sons in all four populations lived longer than females with few sons. The higher cost of sons over daughters on maternal lifespan reported by some human studies may be the exception rather than the rule in long-lived iteroparous species

Herbivore management for biodiversity conservation: A case study of kangaroos in the Australian Capital Territory (ACT)

Populations of macropods are higher than estimated pre-European densities in many parts of Australia. To achieve appropriate densities of macropods in the Australian Capital Territory's nature reserves, multi-tenure kangaroo management units are used to tailor management of kangaroos and total grazing pressure to achieve conservation objectives. An adaptive management framework is recommended that monitors the state of the ground-layer vegetation and alters the cull accordingly. This case study may provide insights for kangaroo management in other temperate areas of Australia

Protecting biodiversity in British Columbia: Recommendations for developing species at risk legislation

British Columbia has the greatest biological diversity of any province or territory in Canada. Yet increasing numbers of species in British Columbia are threatened with extinction. The current patchwork of provincial laws and regulations has not effectively prevented species declines. Recently, the Provincial Government has committed to enacting an endangered species law. Drawing upon our scientific and legal expertise, we offer recommendations for key features of endangered species legislation that build upon strengths and avoid weaknesses observed elsewhere. We recommend striking an independent Oversight Committee to provide recommendations about listing species, organize Recovery Teams, and monitor the efficacy of actions taken. Recovery Teams would evaluate and prioritize potential actions for individual species or groups of species that face common threats or live in a common area, based on best available evidence (including natural and social science and Indigenous Knowledge). Our recommendations focus on implementing an adaptive approach, with ongoing and transparent monitoring and reporting, to reduce delays between determining when a species is at risk and taking effective actions to save it. We urge lawmakers to include this strong evidentiary basis for species recovery as they tackle the scientific and socioeconomic challenges of building an effective species at risk Act

Protecting biodiversity in British Columbia: Recommendations for developing species at risk legislation

British Columbia has the greatest biological diversity of any province or territory in Canada. Yet increasing numbers of species in British Columbia are threatened with extinction. The current patchwork of provincial laws and regulations has not effectively prevented species declines. Recently, the Provincial Government has committed to enacting an endangered species law. Drawing upon our scientific and legal expertise, we offer recommendations for key features of endangered species legislation that build upon strengths and avoid weaknesses observed elsewhere. We recommend striking an independent Oversight Committee to provide recommendations about listing species, organize Recovery Teams, and monitor the efficacy of actions taken. Recovery Teams would evaluate and prioritize potential actions for individual species or groups of species that face common threats or live in a common area, based on best available evidence (including natural and social science and Indigenous Knowledge). Our recommendations focus on implementing an adaptive approach, with ongoing and transparent monitoring and reporting, to reduce delays between determining when a species is at risk and taking effective actions to save it. We urge lawmakers to include this strong evidentiary basis for species recovery as they tackle the scientific and socioeconomic challenges of building an effective species at risk Act

Selection of Reserves for Woodland Caribou Using an Optimization Approach

Habitat protection has been identified as an important strategy for the conservation of woodland caribou (Rangifer tarandus). However, because of the economic opportunity costs associated with protection it is unlikely that all caribou ranges can be protected in their entirety. We used an optimization approach to identify reserve designs for caribou in Alberta, Canada, across a range of potential protection targets. Our designs minimized costs as well as three demographic risk factors: current industrial footprint, presence of white-tailed deer (Odocoileus virginianus), and climate change. We found that, using optimization, 60% of current caribou range can be protected (including 17% in existing parks) while maintaining access to over 98% of the value of resources on public lands. The trade-off between minimizing cost and minimizing demographic risk factors was minimal because the spatial distributions of cost and risk were similar. The prospects for protection are much reduced if protection is directed towards the herds that are most at risk of near-term extirpation

Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor

NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species

Fluctuating optimum and temporally variable selection on breeding date in birds and mammals

International audienceTemporal variation in natural selection is predicted to strongly impact the evolution and demography of natural populations, with consequences for the rate of adaptation, evolution of plasticity, and extinction risk. Most of the theory underlying these predictions assumes a moving optimum phenotype, with predictions expressed in terms of the temporal variance and autocorrelation of this optimum. However, empirical studies seldom estimate patterns of fluctuations of an optimum phenotype, precluding further progress in connecting theory with observations. To bridge this gap, we assess the evidence for temporal variation in selection on breeding date by modeling a fitness function with a fluctuating optimum, across 39 populations of 21 wild animals, one of the largest compilations of long-term datasets with individual measurements of trait and fitness components. We find compelling evidence for fluctuations in the fitness function, causing temporal variation in the magnitude, but not the direction of selection. However, fluctuations of the optimum phenotype need not directly translate into variation in selection gradients, because their impact can be buffered by partial tracking of the optimum by the mean phenotype. Analyzing individuals that reproduce in consecutive years, we find that plastic changes track movements of the optimum phenotype across years, especially in bird species, reducing temporal variation in directional selection. This suggests that phenological plasticity has evolved to cope with fluctuations in the optimum, despite their currently modest contribution to variation in selection

Demographic and reproductive associations with nematode infection in a long-lived mammal

Infection by macroparasites, such as nematodes, varies within vertebrate host systems; elevated infection is commonly observed in juveniles and males, and, for females, with different reproductive states. However, while such patterns are widely recognized in short-lived model systems, how they apply to long-lived hosts is comparatively understudied. Here, we investigated how infection varies with host age, sex, and female reproduction in a semi-captive population of individually marked Asian elephants Elephas maximus. We carried out 1,977 faecal egg counts (FECs) across five years to estimate nematode loads for 324 hosts. Infection patterns followed an established age-infection curve, whereby calves (5 years) exhibited the highest FECs and adults (45 years) the lowest. However, males and females had similar FECs across their long lifespan, despite distinct differences in life-history strategy and clear sexual dimorphism. Additionally, although mothers invest two years in pregnancy and a further three to five years into lactation, nematode load did not vary with four different measures of female reproduction. Our results provide a much-needed insight into the host-parasite dynamics of a long-lived host; determining host-specific associations with infection in such systems is important for broadening our knowledge of parasite ecology and provides practical applications for wildlife medicine and management