Climate change is likely to lead to increasing population variability and extinction risk. Theoretically, greater population diversity should buffer against rising climate variability, and this ...theory is often invoked as a reason for greater conservation. However, this has rarely been quantified. Here we show how a portfolio approach to managing population diversity can inform metapopulation conservation priorities in a changing world. We develop a salmon metapopulation model in which productivity is driven by spatially distributed thermal tolerance and patterns of short- and long-term climate change. We then implement spatial conservation scenarios that control population carrying capacities and evaluate the metapopulation portfolios as a financial manager might: along axes of conservation risk and return. We show that preserving a diversity of thermal tolerances minimizes risk, given environmental stochasticity, and ensures persistence, given long-term environmental change. When the thermal tolerances of populations are unknown, doubling the number of populations conserved may nearly halve expected metapopulation variability. However, this reduction in variability can come at the expense of long-term persistence if climate change increasingly restricts available habitat, forcing ecological managers to balance society's desire for short-term stability and long-term viability. Our findings suggest the importance of conserving the processes that promote thermal-tolerance diversity, such as genetic diversity, habitat heterogeneity, and natural disturbance regimes, and demonstrate that diverse natural portfolios may be critical for metapopulation conservation in the face of increasing climate variability and change.
BRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of ...veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC).
Patients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1–2 lines of treatment, Eastern Cooperative Oncology Group 0–2, were enrolled. Veliparib was dosed at a volume of 300 mg twice-daily (N = 3), then 400 mg twice-daily (N = 15) days 1–28. The primary end-point was to determine the response rate of veliparib; secondary end-points included progression-free survival (PFS), duration of response, overall survival (OS) and safety.
Sixteen patients were enrolled; male N = 8 (50%). Median age was 52 years (range 43–77). Five (31%) had a BRCA1 and 11 (69%) had a BRCA2 mutation. Fourteen (88%) patients had received prior platinum-based therapy. No confirmed partial responses (PRs) were seen: one (6%) unconfirmed PR was observed at 4 months with disease progression (PD) at 6 months; four (25%) had stable disease (SD), whereas 11 (69%) had PD as best response including one with clinical PD. Median PFS was 1.7 months (95% confidence interval CI 1.57–1.83) and median OS was 3.1 months (95% CI 1.9–4.1). Six (38%) patients had grade III toxicity, including fatigue (N = 3), haematology (N = 2) and nausea (N = 1).
Veliparib was well tolerated, but no confirmed response was observed although four (25%) patients remained on study with SD for ≥ 4 months. Additional strategies in this population are needed, and ongoing trials are evaluating PARPis combined with chemotherapy (NCT01585805) and as a maintenance strategy (NCT02184195).
•Veliparib has modest activity in previously treated germline BRCA-mutated pancreas cancer exposed to prior platinum therapy.•Poly(ADP)-ribose) polymerase (PARP) inhibition in pancreas cancer may be best evaluated in a platinum-sensitive disease setting.•There may be intrinsic differences between PARP inhibitors that explain therapeutic outcomes.
Population and life‐history diversity can buffer species from environmental variability and contribute to long‐term stability through differing responses to varying conditions akin to the stabilizing ...effect of asset diversity on financial portfolios. While it is well known that many salmon populations have declined in abundance over the last century, we understand less about how different dimensions of diversity may have shifted. Specifically, how has diminished wild abundance and increased artificial production (i.e. enhancement) changed portfolios of salmon populations, and how might such change influence fisheries and ecosystems?
We apply modern genetic tools to century‐old sockeye salmon Oncorhynchus nerka scales from Canada's Skeena River watershed to (a) reconstruct historical abundance and age‐trait data for 1913–1947 to compare with recent information, (b) quantify changes in population and life‐history diversity and the role of enhancement in population dynamics, and (c) quantify the risk to fisheries and local ecosystems resulting from observed changes in diversity and enhancement.
The total number of wild sockeye returning to the Skeena River during the modern era is 69% lower than during the historical era; all wild populations have declined, several by more than 90%. However, enhancement of a single population has offset declines in wild populations such that aggregate abundances now are similar to historical levels.
Population diversity has declined by 70%, and life‐history diversity has shifted: populations are migrating from freshwater at an earlier age, and spending more time in the ocean. There also has been a contraction in abundance throughout the watershed, which likely has decreased the spatial extent of salmon provisions to Indigenous fisheries and local ecosystems. Despite the erosion of portfolio strength that this salmon complex hosted a century ago, total returns now are no more variable than they were historically perhaps in part due to the stabilizing effect of artificial production.
Policy implications. Our study provides a rare example of the extent of erosion of within‐species biodiversity over the last century of human influence. Rebuilding a diversity of abundant wild populations—that is, maintaining functioning portfolios—may help ensure that watershed complexes like the Skeena are robust to global change.
Our study provides a rare example of the extent of erosion of within‐species biodiversity over the last century of human influence. Rebuilding a diversity of abundant wild populations—that is, maintaining functioning portfolios—may help ensure that watershed complexes like the Skeena are robust to global change. Photo credit: Prince Rupert Archives.
Loss of nuclear TDP-43 is a hallmark of neurodegeneration in TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 mislocalization results in ...cryptic splicing and polyadenylation of pre-messenger RNAs (pre-mRNAs) encoding stathmin-2 (also known as SCG10), a protein that is required for axonal regeneration. We found that TDP-43 binding to a GU-rich region sterically blocked recognition of the cryptic 3' splice site in
pre-mRNA. Targeting dCasRx or antisense oligonucleotides (ASOs) suppressed cryptic splicing, which restored axonal regeneration and stathmin-2-dependent lysosome trafficking in TDP-43-deficient human motor neurons. In mice that were gene-edited to contain human
cryptic splice-polyadenylation sequences, ASO injection into cerebral spinal fluid successfully corrected
pre-mRNA misprocessing and restored stathmin-2 expression levels independently of TDP-43 binding.
Glacier retreat is rapidly transforming some watersheds, with ramifications for water supply, ecological succession, important species such as Pacific salmon (Oncorhynchus spp.), and cultural uses of ...landscapes. To advance a more holistic understanding of the evolution of proglacial landscapes, we integrate multiple lines of knowledge starting in the early 1900s with contemporary data from the Taaltsux̱éi (Tulsequah) Watershed in British Columbia, Canada. Our objectives were to: 1) synthesize recent historical geography and Indigenous Knowledge, including glacier dynamics, and hydrology; 2) describe the limnology of a proglacial lake; 3) quantify decadal-scale downstream physical floodplain change; and 4) characterize riverine physical, chemical, and biological differences relative to distance from the proglacial lake. Since 1982, the Tulsequah Glacier has receded 0.07 km/yr, exposing a cold, deep, and growing proglacial lake. The downstream floodplain is rapidly changing; satellite imagery analysis revealed a 14 % increase in vegetation from 2003 to 2017 and Indigenous Knowledge described increases in vegetation and wildlife habitat over the last century. Contemporary measurements of physical-chemical water properties differed across sites representing the upper and lower watershed, and mainstem and off-channel habitats. Catches of juvenile salmonids in the upper watershed (closer to the glacier) were mostly limited to warmer, clearer groundwater-fed channels, whereas in the lower watershed there were salmonids in both groundwater-fed and mainstem habitats. There was limited zooplankton taxa diversity from the proglacial lake and benthic macroinvertebrates in the river. Collectively, our synthesis suggests that the transformation of proglacial landscapes experiencing rapid ice loss can be influenced by interlinked abiotic processes of glacier retreat, lake formation, and altered hydrology, as well as corresponding biological processes such as beaver repopulation, wetland formation, and riparian vegetation growth. These factors, along with expected increases to proglacial lake productivity and salmon habitat suitability, are an important consideration for forward-looking watershed management of glacier-fed rivers.
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•Evolving proglacial lake watersheds link to biodiversity and societal needs.•We combined historical geography, Indigenous Knowledge, and contemporary analysis.•Physical-chemical and biological diversity unfolds at the stream-reach scale.•Ice retreat presents opportunities for increased biological productivity downstream.•Studies of proglacial landscapes are urgent as these ecosystems face rapid change.
Fish length back-calculation from hard structures (e.g., scales, otoliths, spines, etc.) is a commonly used method to reconstruct individual growth rates and sizes at age/stage in the absence of an ...intensive sampling-resampling timeseries. However, reliable estimates via these methods require the empirical validation of multiple assumptions about the growth of these hard structures. Here, we focus on reducing bias in scale-based back-calculations and validating proposed improvements using archived scales from a wild population of anadromous steelhead trout (Oncorhynchus mykiss). We first describe a series of back-calculation problems and propose solutions that can be integrated into common back-calculation methods. We then compare back-calculation accuracy, precision, and bias between proposed solutions and traditional forms of two backcalculation methods: Fraser-Lee and Body-Proportional. We discovered that the assumption that rapid growth begins immediately after juvenile steelhead pass downstream of the fish fence (300 m upstream of the ocean) was invalid and required a correction factor to prevent overestimating fish length by an average of 14%. The proposed modified methods we described performed better than traditional back-calculation methods. Overall, these findings can improve estimates of fish length from scale-based back-calculations and illustrate the importance of validating key assumptions.
Future ecological value of emerging habitats must be considered as climate change transforms the planet
As climate change warms Earth, the melting cryosphere creates nascent ecosystems that have ...future value as habitat but that are also the frontlines for resource extraction (
1
). For example, glacier retreat uncovers rivers and valleys that go through rapid ecological succession to provide new habitats for important species, such as moose and Pacific salmon (
2
–
5
). However, mining companies are looking to retreating glaciers for newly exposed mineral deposits (
6
). This proglacial mining is a global pressure, from Greenland to Kyrgyzstan to western Canada (
6
). Yet environmental and mining policies might fail to consider the future ecological value and capacity of emerging habitats. We illustrate these issues below by exploring the overlap of glacial retreat, Pacific salmon future habitats, and mining pressures in western Canada and southern Alaska. Stewardship of glacierized landscapes, and other ecosystems that are being transformed by climate change, urgently need forward-looking science and environmental policy.
Expression of phenotypic plasticity depends on reaction norms adapted to historic selective regimes; anthropogenic changes in these selection regimes necessitate contemporary evolution or declines in ...productivity and possibly extinction. Adaptation of conditional strategies following a change in the selection regime requires evolution of either the environmentally influenced cue (e.g., size-at-age) or the state (e.g., size threshold) at which an individual switches between alternative tactics. Using a population of steelhead (Oncorhynchus mykiss) introduced above a barrier waterfall in 1910, we evaluate how the conditional strategy to migrate evolves in response to selection against migration. We created 9 families and 917 offspring from 14 parents collected from the above- and below-barrier populations. After 1 year of common garden-rearing above-barrier offspring were 11% smaller and 32% lighter than below-barrier offspring. Using a novel analytical approach, we estimate that the mean size at which above-barrier fish switch between the resident and migrant tactic is 43% larger than below-barrier fish. As a result, above-barrier fish were 26% less likely to express the migratory tactic. Our results demonstrate how rapid and opposing changes in size-at-age and threshold size contribute to the contemporary evolution of a conditional strategy and indicate that migratory barriers may elicit rapid evolution toward the resident life history on timescales relevant for conservation and management of conditionally migratory species.
Climate change and human activities are transforming river flows globally, with potentially large consequences for freshwater life. To help inform watershed and flow management, there is a need for ...empirical studies linking flows and fish productivity.
We tested the effects of river conditions and other factors on 22 years of Chinook salmon productivity in a watershed in British Columbia, Canada.
Freshwater conditions during adult salmon migration and spawning, as well as during juvenile rearing, explained a large amount of variation in productivity.
August river flows while salmon fry reared had the strongest effect on productivity—our model predicted that cohorts that experience 50% below average flow in the August of rearing have 21% lower productivity.
These contemporary relationships are set within long‐term changes in climate, land use, and hydrology. Over the last century, average August river discharge decreased by 26%, air temperatures warmed, and water withdrawals increased. Seventeen percent of the watershed was logged in the last 20 years.
Our results suggest that, in order to remain stable, this Chinook salmon population being assessed for legal protection requires substantially higher August flow than previously recommended. Changing flow regimes—driven by watershed impacts and climate change—can threaten imperilled fish populations.
We present an empirical relationship between shifting river flows and the productivity of a salmon population being assessed for legal protection. We show decreasing river flows are strongly linked with decreased productivity of imperiled salmon, with implications for water use, forestry management, and fisheries harvest.
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