Tipping point realized in cod fishery.
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ABSTRACT:
SUBMITTER: Mollmann C
PROVIDER: S-EPMC8275682 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk assessment based on in vitro and in silico testing requires utilizing toxicity pathway information to distinguish adverse outcomes from recoverable adaptive events. Little work has focused on oxidative stresses in human airway for the purposes of predicting adverse responses. We hypothesize that early gene expression-mediated molecular changes could be used to delineate adaptive and adverse responses to environmentally-based perturbations. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure, a model oxidant. Airway derived BEAS-2B cells exposed to 2–10 µM Zn2+ elicited concentration- and time-dependent cytotoxicity. Normal, adaptive, and cytotoxic Zn2+ exposure conditions were determined with traditional apical endpoints, and differences in global gene expression around the tipping point of the responses were used to delineate underlying molecular mechanisms. Bioinformatic analyses of differentially expressed genes indicate early enrichment of stress signaling pathways, including those mediated by the transcription factors p53 and NRF2. After 4 h, 154 genes were differentially expressed (p <0.01) between the adaptive and cytotoxic Zn2+ concentrations. Nearly 40% of the biomarker genes were related to the p53 signaling pathway with 30 genes identified as likely direct targets using a database of p53 ChIP-seq studies. Despite similar p53 activation profiles, these data revealed widespread dampening of p53 and NRF2-related genes as early as 4 h after exposure at higher, unrecoverable Zn2+ exposures. Thus, in our model early increased activation of stress response pathways indicated a recoverable adaptive event. Overall, this study highlights the importance of characterizing molecular mechanisms around the tipping point of adverse responses to better inform HTS paradigms.
2016-04-28 | GSE80733 | GEO
Project description:Background:Although risk factors for poor outcomes and complications have been studied, there remain limited objective criteria to guide surgeons about the timing of arthroplasty. The purpose of this study was to further characterize the tipping-point scores for a group of patient-reported outcome measures (PROMs) in patients undergoing primary shoulder arthroplasty. Methods:We retrospectively reviewed 5670 primary shoulder arthroplasties (1833 anatomic total shoulder arthroplasties and 3837 reverse shoulder arthroplasties [RSAs]) performed over a 10-year period. Preoperative range of motion, PROMs (American Shoulder and Elbow Surgeons, Simple Shoulder Test, and Shoulder Pain and Disability Index scores), and Constant scores were evaluated. The tipping point for each PROM was evaluated. Univariate and multivariate analyses were performed to assess risk factors for lower tipping points. Results:Patients undergoing RSA demonstrated lower tipping points for all range-of-motion parameters as well as American Shoulder and Elbow Surgeons, Shoulder Pain and Disability Index, and Simple Shoulder Test scores. Female sex was predictive of a lower tipping point prior to shoulder arthroplasty, regardless of implant type. When the total shoulder arthroplasty subgroup was evaluated, both female sex and a higher body mass index were shown to be associated with a lower tipping point. Discussion:The choice to undergo shoulder arthroplasty is a multifactorial decision that encompasses both physical and social factors. Female patients and patients undergoing RSA are more likely to accept slightly worse shoulder function prior to making the decision to undergo shoulder arthroplasty.
| S-EPMC6928298 | biostudies-literature
Project description:Background Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have been made in understanding the progression of CKD, key molecular events in complex pathophysiological mechanisms that mark each stage of renal failure remain largely unknown. Changes in plasma protein profiles in different disease stages are important for identification of early diagnostic markers and potential therapeutic targets. The goal of this study was to determine the molecular profile of each CKD stage (from 1 to 5), aiming to specifically point out markedly expressed or downregulated proteins. Methods We performed a cross-sectional shotgun-proteomic study of plasma proteome across CKD stages and compared them to healthy controls. After sample pooling and heparin-column purification we analysed proteomes from healthy to CKD stage 1 through 5 participants’ plasma by liquid-chromatography/mass-spectrometry. Results We identified 298 proteins in all study groups, as well as several outliers. Our results indicate that key events, that may later affect the course of disease progression and the overall pathophysiological background, are most pronounced in CKD stage 2, with an emphasis on inflammation, lipoprotein metabolism, angiogenesis and tissue regeneration. Conclusions Our data is consistent with multiple previous studies in CKD research, but also uncovers previously unknown CKD mediators and brings forth several novel potential protein-candidates which might have a significant impact on the development of diagnostic and therapeutic strategies for CKD. We hypothesize that CKD stage 2 is the tipping point in disease progression and a suitable point in disease course for the development of therapeutic solutions.
2022-08-12 | PXD033427 | Pride
Project description:A challenging and outstanding problem in interdisciplinary research is to understand the interplay between transients and stochasticity in high-dimensional dynamical systems. Focusing on the tipping-point dynamics in complex mutualistic networks in ecology constructed from empirical data, we investigate the phenomena of noise-induced collapse and noise-induced recovery. Two types of noise are studied: environmental (Gaussian white) noise and state-dependent demographic noise. The dynamical mechanism responsible for both phenomena is a transition from one stable steady state to another driven by stochastic forcing, mediated by an unstable steady state. Exploiting a generic and effective two-dimensional reduced model for real-world mutualistic networks, we find that the average transient lifetime scales algebraically with the noise amplitude, for both environmental and demographic noise. We develop a physical understanding of the scaling laws through an analysis of the mean first passage time from one steady state to another. The phenomena of noise-induced collapse and recovery and the associated scaling laws have implications for managing high-dimensional ecological systems.
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Project description:While paleoclimate records show that the Earth System is characterized by several different tipping points, their representation within Earth System models (ESMs) remains poorly constrained. This is because historical observations do not encompass variations large enough to provoke such regime changes, and paleoclimate conditions are rarely used to help develop and tune ESMs, which potentially ignores a rich source of information on abrupt climate change. A critical example is the early to mid-Holocene "greening" and subsequent rapid desertification of the Sahara, which most ESMs fail to reproduce, casting doubt on the representation of land-atmosphere coupling and monsoon dynamics. Here, we show that this greening and abrupt termination can be successfully simulated with one ESM after optimizing uncertain model components using both present-day observations and crucially mid-Holocene (6,000 y before present) reconstructions. The optimized model displays abrupt threshold behavior, which shows excellent agreement with long paleoclimate records that were not used in the original optimization. These results suggest that in order to realistically capture climate-system thresholds, ESMs first need to be conditioned with appropriate paleoclimate information.
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Project description:The Arctic Ocean is an early warning system for indicators and effects of climate change. We use a novel combination of experimental and time-series data on effects of ocean warming and acidification on the commercially important Northeast Arctic cod (Gadus morhua) to incorporate these physiological processes into the recruitment model of the fish population. By running an ecological-economic optimization model, we investigate how the interaction of ocean warming, acidification and fishing pressure affects the sustainability of the fishery in terms of ecological, economic, social and consumer-related indicators, ranging from present day conditions up to future climate change scenarios. We find that near-term climate change will benefit the fishery, but under likely future warming and acidification this large fishery is at risk of collapse by the end of the century, even with the best adaptation effort in terms of reduced fishing pressure.
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Project description:We have analyzed health and physiological aging parameters in male and female Atlantic cod, Gadus morhua, captured in Kattegat, Skagerrak and in Öresund. Gender differences were clearly evident in a number of variables. Males had longer liver telomeres and higher catalase activities than females, while females had higher superoxide dismutase activity, liver somatic index and condition factor. Effects of age were found for males where levels of the antioxidant glutathione and telomere length declined with age, indicating physiological aging. Liver somatic index increased and percentage oxidized glutathione decreased with age. Between-site comparisons of males show that percentage oxidized glutathione and catalase were lowest in Kattegat, whereas protein carbonyls and condition factor were higher in Skagerrak. Females, on the other hand, showed no differences between sites or indications of somatic aging or age-related effects in egg quality, indicating that older and larger female cod are healthy and show no changes in eggs with age. In contrast, males showed indications of physiological aging and lower condition than females. The results emphasize the importance of conserving old mature fish, in particular high egg-productive females, when managing fisheries.
| S-EPMC3507242 | biostudies-literature
Project description:The Amazon rainforest has been proposed as a tipping element of the earth system, with the possibility of a dieback of the entire ecosystem due to deforestation only of parts of the rainforest. Possible physical mechanisms behind such a transition are still subject to ongoing debates. Here, we use a specifically designed model to analyse the nonlinear couplings between the Amazon rainforest and the atmospheric moisture transport from the Atlantic to the South American continent. These couplings are associated with a westward cascade of precipitation and evapotranspiration across the Amazon. We investigate impacts of deforestation on the South American monsoonal circulation with particular focus on a previously neglected positive feedback related to condensational latent heating over the rainforest, which strongly enhances atmospheric moisture inflow from the Atlantic. Our results indicate the existence of a tipping point. In our model setup, crossing the tipping point causes precipitation reductions of up to 40% in non-deforested parts of the western Amazon and regions further downstream. The responsible mechanism is the breakdown of the aforementioned feedback, which occurs when deforestation reduces transpiration to a point where the available atmospheric moisture does not suffice anymore to release the latent heat needed to maintain the feedback.
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Project description:Southern Ocean acidification via anthropogenic CO(2) uptake is expected to be detrimental to multiple calcifying plankton species by lowering the concentration of carbonate ion (CO(3)(2-)) to levels where calcium carbonate (both aragonite and calcite) shells begin to dissolve. Natural seasonal variations in carbonate ion concentrations could either hasten or dampen the future onset of this undersaturation of calcium carbonate. We present a large-scale Southern Ocean observational analysis that examines the seasonal magnitude and variability of CO(3)(2-) and pH. Our analysis shows an intense wintertime minimum in CO(3)(2-) south of the Antarctic Polar Front and when combined with anthropogenic CO(2) uptake is likely to induce aragonite undersaturation when atmospheric CO(2) levels reach approximately 450 ppm. Under the IPCC IS92a scenario, Southern Ocean wintertime aragonite undersaturation is projected to occur by the year 2030 and no later than 2038. Some prominent calcifying plankton, in particular the Pteropod species Limacina helicina, have important veliger larval development during winter and will have to experience detrimental carbonate conditions much earlier than previously thought, with possible deleterious flow-on impacts for the wider Southern Ocean marine ecosystem. Our results highlight the critical importance of understanding seasonal carbon dynamics within all calcifying marine ecosystems such as continental shelves and coral reefs, because natural variability may potentially hasten the onset of future ocean acidification.
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Project description:The rate of ischemic stroke associated with traditional risk factors for patients with atrial fibrillation has declined over the past 2 decades. Furthermore, new and potentially safer anticoagulants are on the horizon. Thus, the balance between risk factors for stroke and benefit of anticoagulation may be shifting.The Markov state transition decision model was used to analyze the CHADS(2) score, above which anticoagulation is preferred, first using the stroke rate predicted for the CHADS(2) derivation cohort, and then using the stroke rate from the more contemporary AnTicoagulation and Risk Factors In Atrial Fibrillation cohort for any CHADS(2) score. The base case was a 69-year-old man with atrial fibrillation. Interventions included oral anticoagulant therapy with warfarin or a hypothetical "new and safer" anticoagulant (based on dabigatran), no antithrombotic therapy, or aspirin. Warfarin is preferred above a stroke rate of 1.7% per year, whereas aspirin is preferred at lower rates of stroke. Anticoagulation with warfarin is preferred even for a score of 0 using the higher rates of the older CHADS(2) derivation cohort. Using more contemporary and lower estimates of stroke risk raises the threshold for use of warfarin to a CHADS(2) score ?2. However, anticoagulation with a "new, safer" agent, modeled on the results of the Randomized Evaluation of Long-Term Anticoagulation Therapy trial of dabigatran, leads to a lowering of the threshold for anticoagulation to a stroke rate of 0.9% per year.Use of a more contemporary estimate of stroke risk shifts the "tipping point," such that anticoagulation is preferred at a higher CHADS(2) score, reducing the number of patients for whom anticoagulation is recommended. The introduction of "new, safer" agents, however, would shift the tipping point in the opposite direction.
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