DIFFERENTIAL DETECTION OF TERRITORIAL AND NON-TERRITORIAL GREATER SANDHILL CRANES IN SUMMER

Abundance estimates allow wildlife managers to make informed management decisions, but differential detectability of individuals can lead to biased estimates of abundance. Our objective was to quantify detectability for non-territorial and territorial sandhill cranes (Grus canadensis tabida) during summer. We hypothesized that territorial sandhill cranes would be detected more often than non-territorial cranes. In 2009, 3 wetland areas were surveyed 2 days per week during the nesting season near Briggsville, Wisconsin. We created capture histories for color-marked territorial (n = 52) and color-marked nonterritorial cranes (n = 23) and used the Huggins closed capture model in program MARK to estimate detection probability and abundance for each group. A priori models were developed that explained daily crane detection over the sampling period using distance from road, territorial status, observation event, and time of season as variables. The best approximating model included the variables territorial status and observation event (AICc weight = 0.92). Probability of detection was higher for territorial (0.11, 95% CI = 0.08-0.14) than for non-territorial ( 0.03, 95% CI = 0.01-0.07) sandhill cranes. In subsequent observation events, detection probability almost doubled to 0.18 (95% CI = 0.17-0.20) for territorial cranes, and almost tripled to 0.11 (95% CI = 0.09-0.14) for non-territorial cranes. Potential reasons for differential detection during subsequent observations include differing degrees of movement by birds and/or an observer effect in which the ability to observe birds or the perception by technicians of birds increased over time

Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner

TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic disruption of GABPβ1L (β1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner. Reducing TERT expression by disrupting β1L culminates in telomere loss and cell death exclusively in TERT promoter mutant cells. Orthotopic xenografting of β1L-reduced, TERT promoter mutant glioblastoma cells rendered lower tumor burden and longer overall survival in mice. These results highlight the critical role of GABPβ1L in enabling immortality in TERT promoter mutant glioblastoma.This work was supported by a generous gift from the Dabbiere family (J.F.C.), the Hana Jabsheh Research Initiative (J.F.C.), NIH grant NCI P50CA097257 (J.F.C. and J.A.D.), NCI P01CA118816-06 (J.F.C.), T32 GM008568 and T32 CA151022 (A.M.), and NCI R01CA163336 (J.S.S.), and the Sontag Foundation Distinguished Scientist Award (J.S.S.). C.F. is supported by a US NIH K99/R00 Pathway to Independence Award (K99GM118909) from the National Institute of General Medical Sciences. Additional support was provided by Fundação para a Ciência e Tecnologia SFRH/BD/88220/2012 (A.X.-M.) and IF/00601/2012 (B.M.C.). J.A.D. is an investigator of the Howard Hughes Medical Institute.info:eu-repo/semantics/publishedVersio

Conservation Challenges for Whooping Cranes (Grus americana) and Greater Sandhill Cranes (Grus Canadensis tabida) in Wisconsin

Abundance estimates allow wildlife managers to make informed management decisions, but differential detectability of individuals can lead to biased estimates of abundance. Sandhill cranes (Grus canadensis) are large-bodied and long-lived, rendering them ideal for mark-recapture estimates, but territorial birds have limited movement when compared to non-territorial birds, which may violate the assumption of equal detectability. Our objective was to quantify differential detectability for non-territorial and territorial sandhill cranes on a breeding ground, and to use this information to estimate population size for each group. We hypothesized that territorial sandhill cranes would be detected more often than non-territorial cranes. In 2009, the International Crane Foundation surveyed three routes in Briggsville, Wisconsin, two days per week with six passes per day. Technicians recorded bird locations on an aerial photograph. We created capture histories for banded territorial (n=52) and banded non-territorial cranes (n=23), and used the Huggins closed capture model in program MARK to estimate detection probability and abundance for each group. We identified a priori models that may explain daily crane detection over the sampling period using distance from road, territoriality, sampling event (first or subsequent sighting), and time of season as variables. We used Akaike’s Information Criterion adjusted for small sample size to rank models. The best approximating model included territoriality and sampling event (AICc weight= 0.92). Probability of detection was higher for territorial (̂= 0.11, CI=0.08-0.14) than for non-territorial (̂=0.03, CI= 0.01-0.07) birds. In subsequent sampling events (each day was considered a sampling event), detection probability almost doubled to 0.18 (CI= 0.17-0.20) for territorial cranes, and almost tripled to 0.11 (CI= 0.09-0.14) for non- territorial cranes. Potential reasons for differential detection include differing degrees of movement by birds and/ or an observer effect in which the ability of observers to spot birds increases over time. We also used the N-mixture model to estimate detection probability and abundance for all cranes in the area (banded and unbanded), and obtained similar results for detection probabilities of banded territorial and banded non-territorial cranes. Abundance estimates for unbanded cranes from the N-mixture model were unrealistically high. Our research demonstrates the importance of differential detection when calculating abundance for sandhill cranes on breeding grounds. In 1941, less than twenty whooping cranes (Grus americana) remained in one wild population wintering at Aransas National Wildlife Refuge, Aransas, Texas (Allen 1952). This population had increased to 257 (95% CI 178-362) in the winter of 2012 (Harrell and Bidwell 2013).The United States Fish and Wildlife Service began reintroducing whooping cranes into Wisconsin in 2001, but this population is not self-sustaining (WCEP 2012) potentially because nest success is low. Several hypotheses have been proposed for low nest success including improper nesting behavior resulting from captive rearing techniques. In addition to typical nesting behaviors, Wisconsin whooping cranes may lack adaptive behaviors for coping with ectoparasites specific to the breeding grounds in Wisconsin. Greater sandhill cranes (G. c. tabida) also breed in Wisconsin, and seem to exhibit adequate nest success. We aimed to identify behaviors that differ between nesting whooping cranes and sandhill cranes to better understand why population growth is limited in the reintroduced population of whooping cranes breeding at Necedah National Wildlife Refuge. From March – June 2014, we observed nesting behavior through trail cameras programmed to take one photo every five minutes. During nesting, we monitored nests until either eggs hatched or nests were abandoned. Nine whooping crane nests and seven sandhill crane nests were used for analysis. We identified behaviors (incubating, away from nest, manipulating nest platform, etc.) in 16,487 sandhill crane and 25,544 whooping crane photographs. Apparent nest success was 0.56 for whooping cranes and 0.57 for sandhill cranes during the 2014 breeding season. All whooping crane nest failures were abandonments while sandhill crane nests failed for various reasons including predation. We used a two way factorial ANOVA with sub-sampling and found that birds on nests where one egg hatched spent significantly more time incubating eggs for both crane species (F (0.5),1,12 =14.24, P = 0.0027). Additionally, whooping cranes spent more time away from nests than sandhill cranes (F(0.5),1,12 =5.3, P = 0.0395) and cranes of both species that had successful nests spent less time away from the nest (F (0.5),1,12 =11.7, P = 0.0051). Cranes with successful nests spent less time manipulating eggs than those with unsuccessful nests (F (0.5),1,12 = 16.97, P = 0.0014). All other behaviors were not significantly different between cranes with successful and those with unsuccessful nests or between whooping cranes and sandhill cranes. At this time, we do not know if birds abandoned nests because the eggs were not fertile or if eggs did not hatch because adults left the nests. Behavior differences are confounded with species, rearing (captive or wild), and genetic differences. We also caution the interpretation of the data because we only monitored 16 total nests over one nesting season. However, this first year of data collection supports our hypothesis that whooping cranes and sandhill cranes exhibit some behavioral differences.U.S. Fish and Wildlife Service, The International Crane Foundation, and the University of Wisconsin – Stevens Point

DIFFERENTIAL DETECTION OF TERRITORIAL AND NON-TERRITORIAL GREATER SANDHILL CRANES IN SUMMER

Abundance estimates allow wildlife managers to make informed management decisions, but differential detectability of individuals can lead to biased estimates of abundance. Our objective was to quantify detectability for non-territorial and territorial sandhill cranes (Grus canadensis tabida) during summer. We hypothesized that territorial sandhill cranes would be detected more often than non-territorial cranes. In 2009, 3 wetland areas were surveyed 2 days per week during the nesting season near Briggsville, Wisconsin. We created capture histories for color-marked territorial (n = 52) and color-marked nonterritorial cranes (n = 23) and used the Huggins closed capture model in program MARK to estimate detection probability and abundance for each group. A priori models were developed that explained daily crane detection over the sampling period using distance from road, territorial status, observation event, and time of season as variables. The best approximating model included the variables territorial status and observation event (AICc weight = 0.92). Probability of detection was higher for territorial (0.11, 95% CI = 0.08-0.14) than for non-territorial ( 0.03, 95% CI = 0.01-0.07) sandhill cranes. In subsequent observation events, detection probability almost doubled to 0.18 (95% CI = 0.17-0.20) for territorial cranes, and almost tripled to 0.11 (95% CI = 0.09-0.14) for non-territorial cranes. Potential reasons for differential detection during subsequent observations include differing degrees of movement by birds and/or an observer effect in which the ability to observe birds or the perception by technicians of birds increased over time

Patient-derived cells from recurrent tumors that model the evolution of IDH-mutant glioma.

BackgroundIDH-mutant lower-grade gliomas (LGGs) evolve under the selective pressure of therapy, but well-characterized patient-derived cells (PDCs) modeling evolutionary stages are lacking. IDH-mutant LGGs may develop therapeutic resistance associated with chemotherapy-driven hypermutation and malignant progression. The aim of this study was to establish and characterize PDCs, single-cell-derived PDCs (scPDCs), and xenografts (PDX) of IDH1-mutant recurrences representing distinct stages of tumor evolution.MethodsWe derived and validated cell cultures from IDH1-mutant recurrences of astrocytoma and oligodendroglioma. We used exome sequencing and phylogenetic reconstruction to examine the evolutionary stage represented by PDCs, scPDCs, and PDX relative to corresponding spatiotemporal tumor tissue and germline DNA. PDCs were also characterized for growth and tumor immortality phenotypes, and PDX were examined histologically.ResultsThe integrated astrocytoma phylogeny revealed 2 independent founder clonal expansions of hypermutated (HM) cells in tumor tissue that are faithfully represented by independent PDCs. The oligodendroglioma phylogeny showed more than 4000 temozolomide-associated mutations shared among tumor samples, PDCs, scPDCs, and PDX, suggesting a shared monoclonal origin. The PDCs from both subtypes exhibited hallmarks of tumorigenesis, retention of subtype-defining genomic features, production of 2-hydroxyglutarate, and subtype-specific telomere maintenance mechanisms that confer tumor cell immortality. The oligodendroglioma PDCs formed infiltrative intracranial tumors with characteristic histology.ConclusionsThese PDCs, scPDCs, and PDX are unique and versatile community resources that model the heterogeneous clonal origins and functions of recurrent IDH1-mutant LGGs. The integrated phylogenies advance our knowledge of the complex evolution and immense mutational load of IDH1-mutant HM glioma

Patient-derived cells from recurrent tumors that model the evolution of IDH-mutant glioma.

BackgroundIDH-mutant lower-grade gliomas (LGGs) evolve under the selective pressure of therapy, but well-characterized patient-derived cells (PDCs) modeling evolutionary stages are lacking. IDH-mutant LGGs may develop therapeutic resistance associated with chemotherapy-driven hypermutation and malignant progression. The aim of this study was to establish and characterize PDCs, single-cell-derived PDCs (scPDCs), and xenografts (PDX) of IDH1-mutant recurrences representing distinct stages of tumor evolution.MethodsWe derived and validated cell cultures from IDH1-mutant recurrences of astrocytoma and oligodendroglioma. We used exome sequencing and phylogenetic reconstruction to examine the evolutionary stage represented by PDCs, scPDCs, and PDX relative to corresponding spatiotemporal tumor tissue and germline DNA. PDCs were also characterized for growth and tumor immortality phenotypes, and PDX were examined histologically.ResultsThe integrated astrocytoma phylogeny revealed 2 independent founder clonal expansions of hypermutated (HM) cells in tumor tissue that are faithfully represented by independent PDCs. The oligodendroglioma phylogeny showed more than 4000 temozolomide-associated mutations shared among tumor samples, PDCs, scPDCs, and PDX, suggesting a shared monoclonal origin. The PDCs from both subtypes exhibited hallmarks of tumorigenesis, retention of subtype-defining genomic features, production of 2-hydroxyglutarate, and subtype-specific telomere maintenance mechanisms that confer tumor cell immortality. The oligodendroglioma PDCs formed infiltrative intracranial tumors with characteristic histology.ConclusionsThese PDCs, scPDCs, and PDX are unique and versatile community resources that model the heterogeneous clonal origins and functions of recurrent IDH1-mutant LGGs. The integrated phylogenies advance our knowledge of the complex evolution and immense mutational load of IDH1-mutant HM glioma

Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner.

TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic disruption of GABPβ1L (β1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner. Reducing TERT expression by disrupting β1L culminates in telomere loss and cell death exclusively in TERT promoter mutant cells. Orthotopic xenografting of β1L-reduced, TERT promoter mutant glioblastoma cells rendered lower tumor burden and longer overall survival in mice. These results highlight the critical role of GABPβ1L in enabling immortality in TERT promoter mutant glioblastoma