A Resource for Discovering Specific and Universal Biomarkers for Distributed Stem Cells

Specific and universal biomarkers for distributed stem cells (DSCs) have been elusive. A major barrier to discovery of such ideal DSC biomarkers is difficulty in obtaining DSCs in sufficient quantity and purity. To solve this problem, we used cell lines genetically engineered for conditional asymmetric self-renewal, the defining DSC property. In gene microarray analyses, we identified 85 genes whose expression is tightly asymmetric self-renewal associated (ASRA). The ASRA gene signature prescribed DSCs to undergo asymmetric self-renewal to a greater extent than committed progenitor cells, embryonic stem cells, or induced pluripotent stem cells. This delineation has several significant implications. These include: 1) providing experimental evidence that DSCs in vivo undergo asymmetric self-renewal as individual cells; 2) providing an explanation why earlier attempts to define a common gene expression signature for DSCs were unsuccessful; and 3) predicting that some ASRA proteins may be ideal biomarkers for DSCs. Indeed, two ASRA proteins, CXCR6 and BTG2, and two other related self-renewal pattern associated (SRPA) proteins identified in this gene resource, LGR5 and H2A.Z, display unique asymmetric patterns of expression that have a high potential for universal and specific DSC identification

Local forage fish abundance influences foraging effort and offspring condition in an endangered marine predator

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.All data will be archived in the Dryad Digital Repository and BirdLife Seabird Tracking Database.1. Understanding the functional relationship between marine predators and their prey is vital to inform ecosystem-based management. However, collecting concurrent data on predator behaviour and their prey at relevant scales is challenging. Moreover, opportunities to study these relationships in the absence of industrial fishing are extremely rare. 2. We took advantage of an experimental fisheries closure to study how local prey abundance influences foraging success and chick condition of Endangered African penguins Spheniscus demersus in the Benguela Ecosystem. 3. We tracked 75 chick-provisioning penguins with GPS-time-depth devices, measured body condition of 569 chicks, quantified the diet of 83 breeding penguins and conducted 12 forage fish hydro-acoustic surveys within a 20 km radius of Robben Island, South Africa, over three years (2011–2013). Commercial fishing for the penguins’ main prey, sardine Sardinops sagax and anchovy Engraulis encrasicolus, was prohibited within this 20 km radius during the study period. 4. Local forage fish abundance explained 60% of the variation in time spent diving for 14 penguins at sea within 2 days of a hydro-acoustic survey. Penguin foraging effort (time spent diving, number of wiggles per trip, number of foraging dives and the maximum distance travelled) increased and offspring body condition decreased as forage fish abundance declined. In addition, quantile regression revealed that variation in foraging effort increased as prey abundance around the colony declined. 5. Policy implications. Our results demonstrate that local forage fish abundance influences seabird foraging and offspring fitness. They also highlight the potential for offspring condition and the mean-variance relationship in foraging behaviour to act as leading indicators of poor prey abundance. By rapidly indicating periods where forage resources are scarce, these metrics could help limit seabird-fisheries competition and aid the implementation of dynamic ocean managemen

Urofaecal glucocorticoid metabolite concentrations in African penguin (Spheniscus demersus) chick populations experiencing different levels of human disturbance

This is the final version. Available on open access from Oxford University Press via the DOI in this recordDespite the importance of ecotourism in species conservation, little is known about the industry’s effects on wildlife. In South Africa, some African penguin (Spheniscus demersus) colonies have become tourist attractions. The species is globally endangered, with population sizes decreasing over the past 40 years. As African penguin chicks are altricial and unable to move away from anthropogenic stressors, it is important to evaluate the effect of tourist activities on baseline glucocorticoid levels as a measure of potential disturbance. Chicks at three study sites within two breeding colonies (Robben Island, Stony Point), with varying levels of exposure to tourism (low/moderate/high) were monitored. Urofaecal samples were collected to determine urofaecal glucocorticoid metabolite (ufGCM) concentrations as an indication of baseline stress physiology. Morphometric measurements were taken to compare body condition between sites. Penguin chicks experiencing low, infrequent human presence had significantly higher mean (± standard deviation) ufGCM levels [1.34 ± 1.70 μg/g dry weight (DW)] compared to chicks experiencing both medium (0.50 ± 0.40 μg/g DW, P = 0.001) and high levels of human presence (0.57 ± 0.47 μg/g DW, P = 0.003). There was no difference in chick body condition across sites. These results suggest that exposure to frequent human activity may induce habituation/desensitization in African penguin chicks. Acute, infrequent human presence was likely an important driver for comparatively higher ufGCM levels in chicks, though several other environmental stressors may also play an important role in driving adrenocortical activity. Nevertheless, as unhabituated chicks experiencing infrequent anthropogenic presence showed significantly higher ufGCM levels, managers and legislation should attempt to minimize all forms of activity around important breeding colonies that are not already exposed to regular tourism. Although the results of this study are crucial for developing enhanced conservation and management protocols, additional research on the long-term effect of anthropogenic activities on African penguin physiology is required.Department of Biodiversity and Conservation Biology at the University of the Western CapeSouth African National Research FoundationEarthwatch Institut

Bayesian inference reveals positive but subtle effects of experimental fishery closures on marine predator demographics

Global forage-fish landings are increasing, with potentially grave consequences for marine ecosystems. Predators of forage fish may be influenced by this harvest, but the nature of these effects is contentious. Experimental fishery manipulations offer the best solution to quantify population-level impacts, but are rare. We used Bayesian inference to examine changes in chick survival, body condition and population growth rate of endangered African penguins Spheniscus demersus in response to 8 years of alternating time–area closures around two pairs of colonies. Our results demonstrate that fishing closures improved chick survival and condition, after controlling for changing prey availability. However, this effect was inconsistent across sites and years, highlighting the difficultly of assessing management interventions in marine ecosystems. Nevertheless, modelled increases in population growth rates exceeded 1% at one colony; i.e. the threshold considered biologically meaningful by fisheries management in South Africa. Fishing closures evidently can improve the population trend of a forage-fish-dependent predator—we therefore recommend they continue in South Africa and support their application elsewhere. However, detecting demographic gains for mobile marine predators from small no-take zones requires experimental time frames and scales that will often exceed those desired by decision makers

SACK-Expanded Hair Follicle Stem Cells Display Asymmetric Nuclear Lgr5 Expression With Non-Random Sister Chromatid Segregation

We investigated the properties of clonally-expanded mouse hair follicle stem cells (HF-SCs) in culture. The expansion method, suppression of asymmetric cell kinetics (SACK), is non-toxic and reversible, allowing evaluation of the cells' asymmetric production of differentiating progeny cells. A tight association was discovered between non-random sister chromatid segregation, a unique property of distributed stem cells (DSCs), like HF-SCs, and a recently described biomarker, Lgr5. We found that nuclear Lgr5 expression was limited to the HF-SC sister of asymmetric self-renewal divisions that retained non-randomly co-segregated chromosomes, which contain the oldest cellular DNA strands, called immortal DNA strands. This pattern-specific Lgr5 association poses a potential highly specific new biomarker for delineation of DSCs. The expanded HF-SCs also maintained the ability to make differentiated hair follicle cells spontaneously, as well as under conditions that induced cell differentiation. In future human cell studies, this capability would improve skin grafts and hair replacement therapies

CXCR6, a Newly Defined Biomarker of Tissue-Specific Stem Cell Asymmetric Self-Renewal, Identifies More Aggressive Human Melanoma Cancer Stem Cells

Background: A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. Conclusions/Significance: The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment

Bayesian inference reveals positive but subtle effects of experimental fishery closures on marine predator demographics

Global forage-fish landings are increasing, with potentially grave consequences for marine ecosystems. Predators of forage fish may be influenced by this harvest, but the nature of these effects is contentious. Experimental fishery manipulations offer the best solution to quantify population-level impacts, but are rare. We used Bayesian inference to examine changes in chick survival, body condition and population growth rate of endangered African penguins Spheniscus demersus in response to 8 years of alternating time-area closures around two pairs of colonies. Our results demonstrate that fishing closures improved chick survival and condition, after controlling for changing prey availability. However, this effect was inconsistent across sites and years, highlighting the difficultly of assessing management interventions in marine ecosystems. Nevertheless, modelled increases in population growth rates exceeded 1% at one colony; i.e. the threshold considered biologically meaningful by fisheries management in South Africa. Fishing closures evidently can improve the population trend of a forage-fish-dependent predator-we therefore recommend they continue in South Africa and support their application elsewhere. However, detecting demographic gains for mobile marine predators from small no-take zones requires experimental time frames and scales that will often exceed those desired by decision makers

The status and conservation of Cape Gannets Morus capensis

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this recordThe Cape Gannet Morus capensis is one of several seabird species that are endemic to the Benguela upwelling ecosystem (BUS), whose populations recently decreased leading to unfavourable Red List classifications. Application of JARA, a Bayesian state-space tool for IUCN Red List assessment, to updated information on areas occupied by and nest densities of breeding Cape Gannets at their six colonies suggested the species should be classified as Vulnerable. However, the rate of decrease of Cape Gannets in their most recent generation exceeded that of the previous generation, primarily as a result of large decreases at Bird Island, Lambert’s Bay, and Malgas Island off South Africa’s west coast. Since the 1960s, there has been an ongoing redistribution of the species from northwest to southeast so that c. 70% of the species now occurs at Bird Island, Algoa Bay, on the eastern border of the BUS. Recruitment rather than adult survival may be limiting the present population, although information on demographic parameters and mortality in fisheries is lacking for colonies in the northern BUS. Major present threats to the species include a substantially decreased availability of their preferred prey in the west, heavy mortality of eggs, chicks and fledglings at and around colonies inflicted by Cape Fur Seals Arctocephalus pusillus and other seabirds, substantial disturbance at colonies caused by Cape Fur Seals attacking adults ashore, oiling and disease

Flexibility but no coordination of visits in provisioning riflemen

Parental care strategies occupy a continuum from fixed investments that are consistent across contexts to flexible behaviour that largely depends on external social and environmental cues. Determining the flexibility of care behaviour is important, as it influences the outcome of investment games between multiple individuals caring for the same brood. We investigated the repeatability of provisioning behaviour and the potential for turn taking among breeders and helpers in a cooperatively breeding bird, the rifleman, Acanthisitta chloris. First, we examined whether nest visit rate is an accurate measure of investment by assessing whether carers consistently bring the same size of food, and whether food size is related to nest visit rate. Our results support the use of visit rate as a valid indicator of parental investment. Next, we calculated the repeatability of visit rate and food size to determine whether these behaviours are fixed individual traits or flexible responses to particular contexts. We found that riflemen were flexible in visit rate, supporting responsive models of care over ‘sealed bids’. Finally, we used runs tests to assess whether individual riflemen alternated visits with other carers, indicative of turn taking. We found little evidence of any such coordination of parental provisioning. We conclude that individual flexibility in parental care appears to arise through factors such as breeding status and brood demand, rather than as a real-time response to social partners

Geolocator tracking seabird migration and moult reveal large-scale temperature-driven isoscapes in the NE Atlantic

This is the final version. Available op open access from Wiley via the DOI in this recordRationale By combining precision satellite-tracking with blood sampling, seabirds can be used to validate marine carbon and nitrogen isoscapes, but it is unclear whether a comparable approach using low-precision light-level geolocators (GLS) and feather sampling can be similarly effective. Methods Here we used GLS to identify wintering areas of northern gannets (Morus bassanus) and sampled winter grown feathers (confirmed from image analysis of non-breeding birds) to test for spatial gradients in δ13C and δ15N in the NE Atlantic. Results By matching winter-grown feathers with the non-breeding location of tracked birds we found latitudinal gradients in δ13C and δ15N in neritic waters. Moreover, isotopic patterns were best explained by sea surface temperature. Similar isotope gradients were found in fish muscle sampled at local ports. Conclusions Our study reveals the potential of using seabird GLS and feathers to reconstruct large-scale isotopic patterns