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opencc-zeroAug 2023View details →

Variable expression of cyanide detoxification and tolerance genes in cyanogenic and acyanogenic white clover (Trifolium repens L.)

Premise of the study: β-cyanoalanine synthase (β-CAS) and alternative oxidase (AOX) play important roles in the ability of plants to detoxify and tolerate hydrogen cyanide (HCN) stress. These functions are critical for all plants, as HCN is produced at low levels during basic metabolic processes, but are likely to be especially important in cyanogenic species, which release high levels of HCN following tissue damage. However, their expression has not been examined in cyanogenic species, nor has it been compared between cyanogenic and acyanogenic genotypes within a species. Methods: We used a natural polymorphism for cyanogenesis in white clover to examine β-CAS and Aox gene expression in relation to cyanogenesis-associated HCN exposure. We identified all β-CAS and Aox gene copies present in the genome, including members of the Aox1, Aox2a and Aox2d subfamilies previously reported in legumes. Expression levels were compared between cyanogenic and acyanogenic genotypes, and under conditions of leaf tissue damage compared to undamaged tissue. Key results: Results indicate that β-CAS and Aox2a expression are differentially elevated in cyanogenic genotypes, and that tissue damage is not required to induce this increased expression. Aox2d, in contrast, appears to be upregulated as a generalized wounding response. Conclusions: These findings suggest a heightened constitutive role for both HCN detoxification (via elevated β-CAS expression) and HCN-toxicity mitigation (via elevated Aox2a expression) in plants that are capable of cyanogenesis. As such, freezing-induced cyanide autotoxicity is unlikely to be the primary selective factor in the evolution of climate-associated cyanogenesis clines.

Cold comfort: metabolic rate and tolerance to low temperatures predict latitudinal distribution in ants

Metabolic compensation has been proposed as a mean for ectotherms to cope with colder climates. For example, under the metabolic cold adaptation and the metabolic homeostasis hypotheses (MCA and MHH), it has been formulated that cold-adapted ectotherms should display both higher (MCA) and more thermally sensitive (MHH) metabolic rates (MRs) at lower temperatures. However, whether such compensation can truly be associated with distribution, and whether it interplays with cold-tolerance to support species' climatic niches, remains largely unclear despite broad ecological implications thereof. Here, we teased apart the relationship between MRs, cold-tolerance, and distribution, to test the MCA/MHH among 13 ant species. We report clear metabolic compensation effects, consistent with the MCA and MHH, where MR parameters strongly correlated with latitude and climatic factors across species' distributions. The combination of both cold-tolerance and MR further upheld the best predictions of species' climatic niches. To our knowledge, this is the first study showing that the association of metabolic data with cold-tolerance supports better predictive models of climatic temperature and distribution in social insects than models including cold-tolerance alone. These results also highlight that adaptation to higher latitudes in ants involved adjustments of both cold-tolerance and MRs, to allow this extremely successful group of insects to thrive under colder climates.

opencc-by-4.0Sep 2023View details →

zenodo36/100

Mitochondrial responses to long-term and cyclic hypoxia depend on the oxidized fuel in a hypoxia-tolerant marine bivalve Crassostrea gigas

These are the metadata for a publication "Mitochondrial responses to long-term and cyclic hypoxia depend on the oxidized fuel in a hypoxia-tolerant marine bivalve Crassostrea gigas" under consideration for publication in the Scientific reports. Sessile benthic organisms like oysters inhabits intertidal zone transitioning between aquatic and terrestrial condition during tidal movements exposing the organisms to alternating hypoxia and reoxygenation (H/R) episodes thereby altering the respiratory chain activities and metabolome compositions. Our study investigated the effects of constant long-term H/R stress (90 min at ~0% O2, and 10 min reoxygenation) and constant cyclic H/R stress (5 cycles of 15 min at ~0% O2, and 10 min reoxygenation) on isolated mitochondria from the gill and the digestive gland of C. gigas respiring on different substrates (pyruvate, palmitate, and succinate). Both gill and the digestive gland mitochondria exposed to constant long-term H/R suppressed OXPHOS respiration especially during Complex I oxidation with no change in ROS efflux but an increase FEL. In the gill mitochondria oxidizing Complex I substrates, exposure to constant cyclic H/R prompted a significant drop after the first H/R cycle. In contrast, succinate-driven respiration only showed significant decline after the fifth H/R cycle. ROS efflux and FEL however saw little to no change after constant cyclic H/R. This observation from our study further suggests succinate as a potential stress fuel under H/R stress and might assist in post-hypoxic recovery of oysters mitigating oxidative stress and supporting rapid ATP re-synthesis during oxygen fluctuations such as commonly observed in intertidal zones. Additionally, our study revealed that constant long-term hypoxia is more damaging than constant cyclic hypoxia.

Exploring the connection between autophagy and heat-stress tolerance in Drosophila melanogaster

Mechanisms aimed at recovering from heat-induced damages are closely associated with the ability of ectotherms to survive exposure to stressful temperatures. Autophagy, a ubiquitous stress-responsive catabolic process, has recently gained renewed attention as one of these mechanisms. By increasing the turnover of cellular structures as well as the clearance of long-lived protein and protein aggregates, the induction of autophagy has been linked to increased tolerance to a range of abiotic stressors in diverse ectothermic organisms. However, whether a link between autophagy and heat-tolerance exists in insect models remains unclear despite broad ecophysiological implications thereof. Here, we explored the putative association between autophagy and heat-tolerance using Drosophila melanogaster as a model. We hypothesized that (i) heat-stress would cause an increase of autophagy in flies' tissues, and (ii) rapamycin exposure would trigger a detectable autophagic response in adults and increase their heat-tolerance. In line with our hypothesis, we report that flies exposed to heat-stress present signs of protein aggregation and appear to trigger an autophagy-related homoeostatic response as a result. We further show that rapamycin feeding causes the systemic effect associated with target of rapamycin (TOR) inhibition, induces autophagy locally in the fly gut, and increases the heat-stress tolerance of individuals. These results argue in favour of a substantial contribution of autophagy to the heat-stress tolerance mechanisms of insects.

Molecular constraints on tolerance-resistance trade-offs: Is there a cost?

Plants possess myriad defenses against their herbivores, including constitutive and inducible chemical compounds and regrowth strategies known as tolerance. Recent studies have shown that plant tolerance and resistance are positively associated given they are co-localized in the same molecular pathway, the oxidative pentose phosphate pathway. However, given that both defensive strategies utilize carbon skeletons from a shared resource pool in the oxidative pentose phosphate pathway there are likely costs in maintaining both resistance-tolerance strategies. Here we investigate fitness costs in maintaining both strategies by utilizing a double knockout of cyp79B2 and cyp79B3, key enzymes in the biosynthetic process of indole glucosinolates, which convert tryptophan to indole-3-acetaldoxime (IAOx) and is further used to produce indole glucosinolates. These mutant plants are devoid of any indole glucosinolates thus reducing plant resistance. Results show that knocking out indole glucosinolate production and thus one of the resistance pathways leads to an approximate 46% increase in fitness compensation shifting the undercompensating wild-type Columbia-0 to an overcompensating genotype following damage. We discuss the potential mechanistic basis for the observed patterns.

Functional traits and drought strategy predict leaf thermal tolerance

Heat stress imposes an important physiological constraint on native plant species – one that will only worsen with human-caused climate change. Indeed, rising temperatures have already contributed to large-scale plant mortality events across the globe. These impacts may be especially severe in cities, where the urban heat island effect amplifies climate warming. Understanding how plant species will respond physiologically to rising temperatures and how these responses differ among plant functional groups is critical for predicting future biodiversity scenarios and making informed land management decisions. In this study, we evaluated the effects of elevated temperatures on a functionally and taxonomically diverse group of woody native plant species in a restored urban nature preserve in southern California using measurements of chlorophyll fluorescence as an indicator of leaf thermotolerance. Our aim was to determine if species' traits and drought strategies could serve as useful predictors of thermotolerance. We found that leaf thermotolerance differed among species with contrasting drought strategies, and several leaf-level functional traits were significant predictors of thermotolerance thresholds. Drought deciduous species with high specific leaf area, high rates of transpiration, and low water-use efficiency were the most susceptible to heat damage, while evergreen species with sclerophyllous leaves, high relative water content, and high water-use efficiency maintained photosynthetic function at higher temperatures. While these native shrubs and trees are physiologically equipped to withstand relatively high temperatures in this Mediterranean-type climate, hotter conditions imposed by climate change and urbanization may exceed the tolerance thresholds of many species. We show that leaf functional traits and plant drought strategies may serve as useful indicators of species' vulnerabilities to climate change, and this information can be used to guide restoration and conservation in a warmer world.

opencc-by-4.0Sep 2023View details →

zenodo36/100

Dataset for the paper: Emergent Resource Exchange and Tolerated Theft Behavior using Multi-Agent Reinforcement Learning

Data generated from the experiments for the paper "Emergent Resource Exchange and Tolerated Theft Behavior using Multi-Agent Reinforcement Learning"

GRACE: A Study to Compare the Effectiveness, Safety and Tolerability of PREZISTA (Darunavir)/Ritonavir by Gender and Race When Administered With Other Antiretroviral Medications in Human Immunodeficie

ClinicalTrials.gov study NCT00381303. IPD Sharing: Not stated. Countries: 3. Publications: 3.

A Study to Examine the Safety, Tolerability and Effects on Abnormal Bone Formation of REGN2477 in Patients With Fibrodysplasia Ossificans Progressiva

ClinicalTrials.gov study NCT03188666. IPD Sharing: Not stated. Countries: 8. Publications: 4.

Evaluation of Safety, Tolerability, and Antiviral Activity of Chlorcyclizine HCl in Patients With Chronic Hepatitis C

ClinicalTrials.gov study NCT02118012. IPD Sharing: Not stated. Countries: 1. Publications: 1.

Study to Examine Safety, Tolerability, and Effect on Body Weight of Metreleptin Administered in Conjunction With Pramlintide in Obese and Overweight Subjects

ClinicalTrials.gov study NCT00673387. IPD Sharing: Not stated. Countries: 1. Publications: 1.

A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression

ClinicalTrials.gov study NCT02418585. IPD Sharing: Not stated. Countries: 5. Publications: 16.

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in S

ClinicalTrials.gov study NCT00851890. IPD Sharing: Not stated. Countries: 2. Publications: 1.

closedIPD-NOFeb 2026View details →

Safety and Tolerability of PRO-087 Versus Xyel Ofteno® and Systane Ultra®, on the Ocular Surface of Healthy Subjects

ClinicalTrials.gov study NCT03524157. IPD Sharing: NO. Countries: 1. Publications: 1.

A Study to Evaluate the Dose Response Based on the Efficacy, Safety and Tolerability of Bimekizumab in Subjects With Active Psoriatic Arthritis Which is a Type of Inflammatory Arthritis

ClinicalTrials.gov study NCT02969525. IPD Sharing: Not stated. Countries: 6. Publications: 3.

controlledIPD-YESFeb 2026View details →

Efficacy, Safety, and Tolerability Study of Apremilast to Treat Early Oligoarticular Psoriatic Arthritis.

ClinicalTrials.gov study NCT03747939. IPD Sharing: YES. Countries: 11. Publications: 1.

A Long-term Efficacy, Safety, and Tolerability Study of BOTOX® in Patients With Chronic Migraine

ClinicalTrials.gov study NCT01516892. IPD Sharing: Not stated. Countries: 3. Publications: 4.

A Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly in Subjects With Type 2 Diabetes Mellitus (DURATION-5)

ClinicalTrials.gov study NCT00877890. IPD Sharing: Not stated. Countries: 1. Publications: 5.

Safety, Tolerability, and Pharmacokinetics of Multiple Rising Doses of BI 425809 Tablets for 12 Days to Young and Elderly Healthy Male and Female Volunteers and Comparison of Pharmacokinetics of a Sin

ClinicalTrials.gov study NCT02337283. IPD Sharing: Not stated. Countries: 1. Publications: 1.

Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers

ClinicalTrials.gov study NCT00502216. IPD Sharing: Not stated. Countries: 1. Publications: 1.