Genome resource banks (GRBs) have the potential to preserve the genetic diversity of a species over time, yet they are rarely utilized as effective components of conservation breeding programs. ...Advances have been made in reproductive biology, collection and storage techniques, and use of stored gametes for achieving successful reproduction, but there are few guidelines for integrating GRBs into established breeding programs. Here we present basic guidelines, focusing on strategies for the collection, maintenance, and use of semen GRBs for protecting genetic diversity. These guidelines should be applied in the context of the specific purposes and roles of a breeding program's GRB, which will differ among species depending on vulnerability to loss and the status of rescue and conservation efforts. We recommend establishing up to three types of collections: (1) a National Reserve to preserve a species' genetic diversity, to be used only as a last resort; (2) a Savings Account to be used periodically to invigorate a genetically depauperate population; and (3) a Checking Account to be used as a regular part of the breeding program. We present methods for identifying donors to maximize genetic diversity in a GRB, as well as strategies for maintaining and optimally using GRBs.
Three levels of gamete banks, each serving different roles, can enhance conservation breeding programs.
A “National Reserve” is a protected repository to be used only when population survival is at imminent risk.
A “Savings Account” serves to periodically reinvigorate populations.
A “Checking Account” contains semen to be considered as mate options each generation.
Highlights
The establishment and judicious use of three levels of gamete banks, each serving different roles, can enhance the protection of genetic diversity in conservation breeding programs.
A “National Reserve” serves as a protected repository holding to the fullest extent the genetic diversity of a species.
A “Savings Account” serves as a resource to periodically reinvigorate populations suffering from genetic erosion.
A “Checking Account” contains semen from both deceased and living males to be considered as mate options each generation.
We present quantitative methods for determining which males should be sampled to secure the desired genetic diversity in each type of bank.
Population models, such as those used for Population Viability Analysis (PVA), are valuable for projecting trends, assessing threats, guiding environmental resource management, and planning species ...conservation measures. However, rarely are the needed data on all aspects of the life history available for cetacean species, because they are long-lived and difficult to study in their aquatic habitats. We present a detailed assessment of population dynamics for the long-term resident Sarasota Bay common bottlenose dolphin (
Tursiops truncatus
) community. Model parameters were estimated from 27 years of nearly complete monitoring, allowing calculation of age-specific and sex-specific mortality and reproductive rates, uncertainty in parameter values, fluctuation in demographic rates over time, and intrinsic uncertainty in the population trajectory resulting from stochastic processes. Using the Vortex PVA model, we projected mean population growth and quantified causes of variation and uncertainty in growth. The ability of the model to simulate the dynamics of the population was confirmed by comparing model projections to observed census trends from 1993 to 2020. When the simulation treated all losses as deaths and included observed immigration, the model projects a long-term mean annual population growth of 2.1%. Variance in annual growth across years of the simulation (
SD
= 3.1%) was due more to environmental variation and intrinsic demographic stochasticity than to uncertainty in estimates of mean demographic rates. Population growth was most sensitive to uncertainty and annual variation in reproduction of peak breeding age females and in calf and juvenile mortality, while adult survival varied little over time. We examined potential threats to the population, including increased anthropogenic mortality and impacts of red tides, and tested resilience to catastrophic events. Due to its life history characteristics, the population was projected to be demographically stable at smaller sizes than commonly assumed for Minimum Viable Population of mammals, but it is expected to recover only slowly from any catastrophic events, such as disease outbreaks and spills of oil or other toxins. The analyses indicate that well-studied populations of small cetaceans might typically experience slower growth rates (about 2%) than has been assumed in calculations of Potential Biological Removal used by management agencies to determine limits to incidental take of marine mammals. The loss of an additional one dolphin per year was found to cause significant harm to this population of about 150 to 175 animals. Beyond the significance for the specific population, demographic analyses of the Sarasota Bay dolphins provide a template for examining viability of other populations of small cetaceans.
Genetic diversity among and within populations of all species is necessary for people and nature to survive and thrive in a changing world. Over the past three years, commitments for conserving ...genetic diversity have become more ambitious and specific under the Convention on Biological Diversity’s (CBD) draft post-2020 global biodiversity framework (GBF). This Perspective article comments on how goals and targets of the GBF have evolved, the improvements that are still needed, lessons learned from this process, and connections between goals and targets and the actions and reporting that will be needed to maintain, protect, manage and monitor genetic diversity. It is possible and necessary that the GBF strives to maintain genetic diversity within and among populations of all species, to restore genetic connectivity, and to develop national genetic conservation strategies, and to report on these using proposed, feasible indicators.
Abstract
Conservation resources are limited, yet an increasing number of species are under threat. Assessing species for their conservation needs is, therefore, a vital first step in identifying and ...prioritizing species for both ex situ and in situ conservation actions. Using a transparent, logical and objective method, the Conservation Needs Assessment process developed by Amphibian Ark uses current knowledge of species in the wild to determine those with the most pressing conservation needs, and provides a foundation for the development of holistic conservation action plans that combine in situ and ex situ actions as appropriate. These assessments allow us to maximize the impact of limited conservation resources by identifying which measures could best serve those species requiring help. The Conservation Needs Assessment complements the IUCN Red List assessment, and together they provide a more holistic guide to conservation priorities and actions. Conservation Needs Assessments generate national prioritized lists of species recommended for conservation action. These can subsequently be used to assist in the development of species recovery plans and national action plans, or to inform national conservation priorities better. Additional tools that will evaluate the recommendations for ex situ rescues, to determine the best candidates for conservation breeding programmes, are currently under development.
In appropriately selected patients with AL amyloidosis, autologous stem cell transplant (ASCT) is an established treatment modality with excellent outcomes and decreasing transplant related mortality ...(TRM) over time. We report on 15-year overall survival (OS) in 159 patients undergoing ASCT from 1996 to 2003, with median follow up of 17.1 years. Day 100 TRM was 13.2% (n = 21). The OS of ≥15 years was observed in 30% (47/159) of patients. Patients surviving ≥15 years were younger (53 vs 56 years, P = .02), less likely to have lambda as the involved light chain (62% vs 78%, P = .03) and were less likely to have heart involvement (32% vs 56%, P = .005). Median OS of patients with heart involvement vs not was 4.0 vs 11.1 years, P = .006 and actuarial 15-year OS was 23% vs 43%, respectively. A higher proportion of patients with OS ≥15 years received full-dose melphalan conditioning (81% vs 61%, P = .01), and achieved day 100 complete response (CR) (64% vs 24%, P < .001). Median OS amongst patients who achieved CR vs not was 19.3 vs 5.4 years, P < .001. Heart involvement, receiving full-dose melphalan and achieving CR remained independent predictors of OS. AL amyloidosis and related complications were the cause of death in 52% of patients overall (1-5 years post-transplant: 81%; 5-10 years: 62% and 10-15 years: 55%). These results reinforce the key role of ASCT in AL amyloidosis. With improvements in TRM and more options for relapsed disease, we expect the long-term survival post-transplant to improve significantly in the future.
Population viability analysis (PVA) utilizes simulation models to project the genetic and demographic trajectories of populations over time. One benefit to using PVA to assist in ex situ population ...planning is the ability to compare outcomes from multiple management scenarios. Reproductive viability analysis (RVA), used to identify biological and reproductive characteristics of animals in breeding pairs that correlate with successful reproduction, is also beneficial, informing population managers on best practices for population planning. Our objectives were to: (1) compare genetic and demographic predictions for the managed North American ex situ fennec fox population from two PVA programs: Vortex and ZooRisk; (2) show how RVA results can be incorporated into PVAs in Vortex and how that affects PVA projections; and (3) perform a sensitivity analysis to investigate how uncertainty in the influence of factors on the reproductive success of fennec fox pairs affects variation in population projections. In this study, the relative and average genetic and demographic predictions were generally the same across both software programs when given similar inputs. The inclusion of factors that influence breeding success (RVA) in the PVA models resulted in a lower probability of extinction, less inbreeding accumulation, and slower loss of genetic diversity, due to an overall higher rate of reproductive success. The uncertainty in the negative effects of increasing female and male age, and the positive effect of female parity on reproductive success had the greatest effect on projected genetic diversity and inbreeding. Our study demonstrates that Vortex is capable of projecting the viability of ex situ populations with flexibility, and has the ability to incorporate complexity and uncertainty into population parameters. It also reveals that adjusting ex situ population management, more specifically the consideration of factors affecting reproductive success to create breeding pairs with a higher probability of success, will improve population sustainability.
Population viability analysis (PVA) utilizes simulation models to project the genetic and demographic trajectories of populations over time. One benefit to using PVA to assist in ex situ population planning is the ability to compare outcomes from multiple management scenarios. Reproductive viability analysis (RVA), used to identify biological and reproductive characteristics of animals in breeding pairs that correlate with successful reproduction, is also beneficial, informing population managers on best practices for population planning and may help improve demographic predictions. Here we build on traditional PVA modeling methods, illustrating how to incorporate the results from an RVA into a PVA, and what effect this has on genetic and demographic projections as a result. Though we use the ex situ fennec fox population as the model species in this study, these methods could be generalized across a large range of taxa
Abstract Wildlife species and populations are being driven toward extinction by a combination of historic and emerging stressors (e.g., overexploitation, habitat loss, contaminants, climate change), ...suggesting that we are in the midst of the planet’s sixth mass extinction. The invisible loss of biodiversity before species have been identified and described in scientific literature has been termed, memorably, dark extinction. The critically endangered Southern Resident killer whale ( Orcinus orca ) population illustrates its contrast, which we term bright extinction; namely the noticeable and documented precipitous decline of a data-rich population toward extinction. Here we use a population viability analysis to test the sensitivity of this killer whale population to variability in age structure, survival rates, and prey-demography functional relationships. Preventing extinction is still possible but will require greater sacrifices on regional ocean use, urban development, and land use practices, than would have been the case had threats been mitigated even a decade earlier.
Small populations lose genetic variability because of genetic drift, and inbreeding within populations can further decrease individual variability. Lower variation depresses individual fitness, ...resistance to disease and parasites, and flexibility in coping with environmental challenges. Lower variation decreases mean fitness of populations (population growth rates), resilience, and long-term adaptability. Genetic drift can threaten viability of populations not just by depleting variation, but also by replacing natural selection as the predominant force driving evolutionary change. Although most genetic studies use laboratory or domesticated populations, evidence is accumulating that the effects of inbreeding are at least as severe on wild animals in natural habitats. Natural selection is expected to reduce the frequency of deleterious alleles in populations that persist through bottlenecks, but as yet there is little evidence for such purging of the genetic load in mammalian populations. No species of mammal has been shown to be unaffected by inbreeding. Genetic problems are contributing to the decline and vulnerability of at least several mammalian taxa. Genetic threats to population viability will be expressed through their effects on and interactions with demographic and ecological processes. Theoretical analyses, experimental tests, field studies, and conservation actions should recognize the fundamental interdependency of genetic and non-genetic processes affecting viability of populations.
Stochastic simulation models requiring many input parameters are widely used to inform the management of ecological systems. The interpretation of complex models is aided by global sensitivity ...analysis, using simulations for distinct parameter sets sampled from multidimensional space. Ecologists typically analyze such output using an “emulator”; that is, a statistical model used to approximate the relationship between parameter inputs and simulation outputs and to derive sensitivity measures. However, it is typical for ad hoc decisions to be made regarding: (1) trading off the number of parameter samples against the number of simulation iterations run per sample, (2) determining whether parameter sampling is sufficient, and (3) selecting an appropriate emulator. To evaluate these choices, we coupled different sensitivity‐analysis designs and emulators for a stochastic, 20‐parameter model that simulated the re‐introduction of a threatened species subject to predation and disease, and then validated the emulators against new output generated from the simulation model. Our results lead to the following sensitivity analysis‐protocol for stochastic ecological models. (1) Run a single simulation iteration per parameter sample generated, even if the focal response is a probabilistic outcome, while sampling extensively across the parameter space. In contrast to designs that invested in many model iterations (tens to thousands) per parameter sample, this approach allowed emulators to capture the input‐output relationship of the simulation model more accurately and also to produce sensitivity measures that were robust to variation inherent in the parameter‐sampling stage. (2) Confirm that parameter sampling is sufficient, by emulating subsamples of the sensitivity‐analysis output. As the subsample size is increased, the cross‐validatory performance of the emulator and sensitivity measures derived from it should exhibit asymptotic behavior. This approach can also be used to compare candidate emulators and select an appropriate interaction depth. (3) If required, conduct further simulations for additional parameter samples, and then report sensitivity measures and illustrate key response curves using the selected emulator. This protocol will generate robust sensitivity measures and facilitate the interpretation of complex ecological models, while minimizing simulation effort.
Single-chain fragment variable (scFv) domains play an important role in antibody-based therapeutic modalities, such as bispecifics, multispecifics and chimeric antigen receptor T cells or natural ...killer cells. However, scFv domains exhibit lower stability and increased risk of aggregation due to transient dissociation ("breathing") and inter-molecular reassociation of the two domains (VL and VH). We designed a novel strategy, referred to as stapling, that introduces two disulfide bonds between the scFv linker and the two variable domains to minimize scFv breathing. We named the resulting molecules stapled scFv (spFv). Stapling increased thermal stability (Tm) by an average of 10°C. In multiple scFv/spFv multispecifics, the spFv molecules display significantly improved stability, minimal aggregation and superior product quality. These spFv multispecifics retain binding affinity and functionality. Our stapling design was compatible with all antibody variable regions we evaluated and may be widely applicable to stabilize scFv molecules for designing biotherapeutics with superior biophysical properties.
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