Inter-aviary distance and visual access influence conservation breeding outcomes in a territorial, endangered bird

Funding for setting up the housing database was provided by the UK’s Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/G023913/2 to C.R.).Species extinctions are becoming a global crisis, affecting biodiversity and ecosystem services, with island populations being particularly vulnerable. In response, conservation managers are increasingly turning to ex situ conservation breeding programs to establish assurance populations and provide a source for release and re-establishment of wild populations. The 'Alalā (Hawaiian crow, Corvus hawaiiensis) is a critically endangered and territorial island corvid that became extinct in the wild in 2002, following a severe and prolonged population decline during the late 20th century. Surviving individuals of the species were brought into captivity to establish an assurance population to serve as a source for reintroduction, which commenced in 2016. We analyzed the extent to which a range of captive housing conditions impact 'Alalā reproductive success, using 19 years of breeding program data. We found that reproductive success was most strongly affected by the distance between aviaries and their closest neighbors and whether breeding pairs had visual access to other adult conspecifics. Pairs located in aviaries that were more spatially isolated and without visual access to conspecifics were more likely to produce fertile eggs than pairs housed in aviaries that were closer to others or those with visual access to other birds. Our results have direct management implications relevant to the design of conservation breeding centers geared towards the recovery of endangered, territorial bird species. Moreover, since suboptimal housing conditions can increase stress levels in captive birds, our findings are also relevant to improving animal welfare for 'Alalā and other species in conservation breeding programs.PostprintPeer reviewe

Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways

Abstract Introduction Mammary-specific overexpression of Six1 in mice induces tumors that resemble human breast cancer, some having undergone epithelial to mesenchymal transition (EMT) and exhibiting stem/progenitor cell features. Six1 overexpression in human breast cancer cells promotes EMT and metastatic dissemination. We hypothesized that Six1 plays a role in the tumor initiating cell (TIC) population specifically in certain subtypes of breast cancer, and that by understanding its mechanism of action, we could potentially develop new means to target TICs. Methods We examined gene expression datasets to determine the breast cancer subtypes with Six1 overexpression, and then examined its expression in the CD24low/CD44+ putative TIC population in human luminal breast cancers xenografted through mice and in luminal breast cancer cell lines. Six1 overexpression, or knockdown, was performed in different systems to examine how Six1 levels affect TIC characteristics, using gene expression and flow cytometric analysis, tumorsphere assays, and in vivo TIC assays in immunocompromised and immune-competent mice. We examined the molecular pathways by which Six1 influences TICs using genetic/inhibitor approaches in vitro and in vivo. Finally, we examined the expression of Six1 and phosphorylated extracellular signal-regulated kinase (p-ERK) in human breast cancers. Results High levels of Six1 are associated with adverse outcomes in luminal breast cancers, particularly the luminal B subtype. Six1 levels are enriched in the CD24low/CD44+ TIC population in human luminal breast cancers xenografted through mice, and in tumorsphere cultures in MCF7 and T47D luminal breast cancer cells. When overexpressed in MCF7 cells, Six1expands the TIC population through activation of transforming growth factor-beta (TGF-β) and mitogen activated protein kinase (MEK)/ERK signaling. Inhibition of ERK signaling in MCF7-Six1 cells with MEK1/2 inhibitors, U0126 and AZD6244, restores the TIC population of luminal breast cancer cells back to that observed in control cells. Administration of AZD6244 dramatically inhibits tumor formation efficiency and metastasis in cells that express high levels of Six1 ectopically or endogenously. Finally, we demonstrate that Six1 significantly correlates with phosphorylated ERK in human breast cancers. Conclusions Six1 plays an important role in the TIC population in luminal breast cancers and induces a TIC phenotype by enhancing both TGF-β and ERK signaling. MEK1/2 kinase inhibitors are potential candidates for targeting TICs in breast tumors

Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer

Pre-release training, predator interactions and evidence for persistence of anti-predator behavior in reintroduced `alalā, Hawaiian crow

Animal translocations commonly fail due to predation after release, especially if animals are reared in human care, away from natural predation pressure. Anti-predator training can be a useful tool for combating the predator naivety of released animals, but its effective implementation requires attention to numerous details. We present the step-by-step development of an anti-predator training regime, tailored to the critically endangered `alalā (Corvus hawaiiensis). `Alalā are the last remaining corvid species of the Hawaiian islands, and historically the level of predation they experienced from the Hawaiian hawk, `io (Buteo solitarius) is unclear. However, one factor thought to compromise outcomes of earlier attempts to reintroduce `alalā in the 1990′s was predation by `io, motivating the development of anti-predator training for recent `alalā releases. We documented evidence for what appears to be competent anti-predator behavior in conservation-bred `alalā, with a range of behavioral strategies for coping with `io observed during a series of controlled presentations of `io and `io-related stimuli. These behavioral responses included vigilance, alarm calling, and mobbing during experimental trials conducted in release training aviaries. Our results did not conclusively establish that anti-predator learning occurred as a result of the training, or that the training produced enhanced survival. However, following release, `io-`alalā encounters were observed on more than 35 occasions, and `alalā responses mirrored those observed pre-release, including the first ever recorded mobbing interactions by juvenile flocks of `alalā in the wild. While it is unclear the extent to which training encouraged these species-appropriate anti-predator responses, their occurrence suggests that the `alalā has retained and can express defensive behavioral strategies. By documenting the design process, training execution and behavioral outcomes in `alalā, we highlight details that other reintroduction programs may need to consider when preparing animals for reintroduction alongside natural predators

Rodent control and food supplementation increase productivity of endangered San Clemente Loggerhead Shrikes (Lanius ludovicianus mearnsi)

period produced a mean of 1.9 fledglings. Pairs receiving both food and rat control produced an average of 2.5 more fledglings than pairs receiving no management, while pairs receiving rat control alone produced an average of 1.1 more fledglings than pairs receiving no management during this period. Wild-origin females produced an average of 0.8 more fledglings per pair than captive-origin females, while older males produced an average of 0.9 more fledglings and independent young relative to inexperienced males. The effects of food supplementation and rat control on San Clemente Loggerhead Shrikes were most pronounced during dry years, suggesting such management should be emphasized when prebreeding precipitation levels are below historical averages. These techniques offer an effective means to increase breeding productivity of avian species in immediate threat of extinction