Potential for ecological nonlinearities and thresholds to inform Pacific salmon management

AbstractEcology is often governed by nonlinear dynamics. Nonlinear ecological relationships can include thresholds—incremental changes in drivers that provoke disproportionately large ecological responses. Among the species that experience nonlinear and threshold dynamics are Pacific salmon (Oncorhynchus spp.). These culturally, ecologically, and economically significant fishes are in many places declining and management focal points. Often, managers can influence or react to ecological conditions that salmon experience, suggesting that nonlinearities, especially thresholds, may provide opportunities to inform decisions. However, nonlinear dynamics are not always invoked in management decisions involving salmon. Here, we review reported nonlinearities and thresholds in salmon ecology, describe potential applications that scientists and managers could develop to leverage nonlinear dynamics, and offer a path toward decisions that account for ecological nonlinearities and thresholds to improve salmon outcomes. It appears that nonlinear dynamics are not uncommon in salmon ecology and that many management arenas may potentially leverage them to enable more effective or efficient decisions. Indeed, decisions guided by nonlinearities and thresholds may be particularly desirable considering salmon management arenas are often characterized by limited resources and mounting ecological stressors, practical constraints, and conservation challenges. More broadly, many salmon systems are data‐rich and there are an extensive range of ecological contexts in which salmon are sensitive to anthropogenic decisions. Approaches developed to leverage nonlinearities in salmon ecology may serve as examples that may inform analogous approaches in other systems and taxa

Climate vulnerability assessment for Pacific salmon and steelhead in the California Current Large Marine Ecosystem.

Major ecological realignments are already occurring in response to climate change. To be successful, conservation strategies now need to account for geographical patterns in traits sensitive to climate change, as well as climate threats to species-level diversity. As part of an effort to provide such information, we conducted a climate vulnerability assessment that included all anadromous Pacific salmon and steelhead (Oncorhynchus spp.) population units listed under the U.S. Endangered Species Act. Using an expert-based scoring system, we ranked 20 attributes for the 28 listed units and 5 additional units. Attributes captured biological sensitivity, or the strength of linkages between each listing unit and the present climate; climate exposure, or the magnitude of projected change in local environmental conditions; and adaptive capacity, or the ability to modify phenotypes to cope with new climatic conditions. Each listing unit was then assigned one of four vulnerability categories. Units ranked most vulnerable overall were Chinook (O. tshawytscha) in the California Central Valley, coho (O. kisutch) in California and southern Oregon, sockeye (O. nerka) in the Snake River Basin, and spring-run Chinook in the interior Columbia and Willamette River Basins. We identified units with similar vulnerability profiles using a hierarchical cluster analysis. Life history characteristics, especially freshwater and estuary residence times, interplayed with gradations in exposure from south to north and from coastal to interior regions to generate landscape-level patterns within each species. Nearly all listing units faced high exposures to projected increases in stream temperature, sea surface temperature, and ocean acidification, but other aspects of exposure peaked in particular regions. Anthropogenic factors, especially migration barriers, habitat degradation, and hatchery influence, have reduced the adaptive capacity of most steelhead and salmon populations. Enhancing adaptive capacity is essential to mitigate for the increasing threat of climate change. Collectively, these results provide a framework to support recovery planning that considers climate impacts on the majority of West Coast anadromous salmonids

CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence

Summary. Abnormal increases in cell size are associated with senescence and cell cycle exit. The mechanisms by which overgrowth primes cells to withdraw from the cell cycle remain unknown. We address this question using CDK4/6 inhibitors, which arrest cells in G0/G1 and are licensed to treat advanced HR+/HER2− breast cancer. We demonstrate that CDK4/6-inhibited cells overgrow during G0/G1, causing p38/p53/p21-dependent cell cycle withdrawal. Cell cycle withdrawal is triggered by biphasic p21 induction. The first p21 wave is caused by osmotic stress, leading to p38- and size-dependent accumulation of p21. CDK4/6 inhibitor washout results in some cells entering S-phase. Overgrown cells experience replication stress, resulting in a second p21 wave that promotes cell cycle withdrawal from G2 or the subsequent G1. We propose that the levels of p21 integrate signals from overgrowth-triggered stresses to determine cell fate. This model explains how hypertrophy can drive senescence and why CDK4/6 inhibitors have long-lasting effects in patients

Animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (frst detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the fndings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.info:eu-repo/semantics/acceptedVersio

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response

A Comprehensive Review of the Impacts of Climate Change on Salmon: Strengths and Weaknesses of the Literature by Life Stage

As we confront novel environmental challenges, a full understanding of the physical and biological processes that govern species responses to climate change will help maintain biodiversity and support conservation measures that are more robust to irreducible uncertainty. However, climate impacts are so complex, and the literature on salmon and trout is so vast that researchers and decision makers scramble to make sense of it all. Therefore, we conducted a systematic literature review of climate impacts on salmon and anadromous trout as a resource for stakeholders, managers, and researchers. We reviewed studies published from 2010 to 2021 that address climate impacts on these fish and organized them in a database of 1169 physical and 1853 biological papers. Papers are labeled with keywords across eight categories related to subject matter and study methods. We compared the literature by biological process and life stage and used these comparisons to assess strengths and weaknesses. We then summarized expected phenotypic and genetic responses and management actions by life stage. Overall, we found the largest research gaps related to species interactions, behavioral responses, and effects that carry over across life stages. With this collection of the literature, we can better apply scarce conservation resources, fill knowledge gaps, and make informed decisions that do not ignore uncertainty

sockeye.datafile

This data comes primarily from the Columbia River DART database managed by the University of Washington (http://www.cbr.washington.edu/dart/dart.html). Column headings: Y=Year of adult migration; D=median migrate date of adult sockeye salmon (DART); S1997=selection differential calculated in R based on the selection function fit to 1997 mark-recapture data; F=mean June flow in cms at Bonneville Dam (DART); FP=day of maximum flow in Julian days, calculated from daily flow data from DART; T=mean June temperature at Bonneville Dam(DART); Umar, Uap,Umay=Upwelling index for March, April, and May at 45N from Pacific Fisheries Environmental Laboratory. 2008. Upwelling Index. Environmental Research Division, NOAA-Fisheries, SWFSC http://www.pfeg.noaa.gov/javamenu.html, accessed June 2008. WRI=total sockeye count at Wells Dam divided by the total count at Rock Island Dam (DART); PDO=Index of the Pacific Decadal Oscillation averaged from Dec-Jun from Mantua, N. 2005. PDO Index, http://jisao.washington.edu/pdo/PDO.latest; NPGO=Di Lorenzo, E., N. Schneider, K. M. Cobb, K. Chhak, P. J. S. Franks, A. J. Miller, J. C. McWilliams et al. 2008. North Pacific Gyre Oscillation NPGO Index available at http://eros.eas.gatech.edu/npgo/; NPI= North Pacific Index, from Trenberth, K., and J. Hurrell. 2009. Boulder, USA, Climate Analysis Section, NCAR. The next set of columns are the difference in the index from year t-4 to year t, except for S4, which is simply shifted by 4 years. CumS4 reflects the cumulative selection at 4-generation intervals up to that year. D.sd is the standard deviation of the migration period, and betaS is the selection differential standardized by the standard deviation of the trait (i.e., D.sd