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12,683 results for “tolerability”
Data from: Health trajectories reveal the dynamic contributions of host genetic resistance and tolerance to infection outcome
Resistance and tolerance are two alternative strategies hosts can adopt to survive infections. Both strategies may be genetically controlled. To date, the relative contribution of resistance and tolerance to infection outcome is poorly understood. A bioluminescent Listeria monocytogenes (Lm) infection challenge model on four genetically diverse mouse strains was used to study the genetic determination and dynamic contributions of host resistance and tolerance to listeriosis, a serious food-borne infectious disease in humans. Conventional statistical analyses revealed significant genetic variation in both resistance and tolerance, but could not capture the time-dependent relative importance of either strategy. These limitations were overcome by the development of novel statistical tools to analyse individual infection trajectories portraying simultaneous changes in infection severity and health. Based on these tools, early expression of resistance followed later by expression of tolerance, emerged as important hallmarks for surviving Lm infections. Trajectory analysis further revealed that survivors and non-survivors follow distinct infection paths, which are also genetically determined, and provided new survival thresholds as objective endpoints in infection experiments. Future studies may use trajectories as novel traits for mapping and identifying genes that control infection dynamics and outcome. A Matlab script for user-friendly trajectory analysis is provided.
Data from: The effect of leaf shape on the thermoregulation and frost tolerance of an annual vine, Ipomoea hederacea (Convolvulaceae)
Premise of study: Leaf shape is predicted to have important ecophysiological consequences; for example, theory predicts that lobed leaves should track air temperature more closely than their entire-margined counterparts. Hence, leaf-lobing may be advantageous during cold nights (∼0°C) when there is the risk of damage by radiation frost (a phenomenon whereby leaves fall below air temperature because of an imbalance between radiational heat loss and convective heat gain). Methods: Here, we test whether radiation frost can lead to differential damage between leaf shapes by examining a leaf-shape polymorphism in Ipomoea hederacea, where leaves are either lobed or heart-shaped depending on a single Mendelian locus. We logged leaf temperature during midautumn, and measured chlorophyll fluorescence and survival as proxies of performance. Furthermore, we tested if the leaf-shape locus confers freezing tolerance using freezing assays on leaf tissue from different leaf shapes. Key results: We found that lobed leaves consistently remain warmer than heart-shaped leaves during the night, but that no pattern emerged during the day, and that temperature differences between leaf shapes were typically small. Furthermore, we found that leaf types did not differ in frost tolerance, but that a 1°C decrease leads to a transition from moderate to complete damage. Conclusions: Our results demonstrate that Ipomoea hederacea leaf shapes do experience different nighttime temperatures, and that only minor temperature differences can lead to disparate levels of freezing damage, suggesting that the differential thermoregulation could result in different levels of frost damage.
Data from: Life-history strategy and behavioral type: risk-tolerance reflects growth rate and energy allocation in ant colonies
Despite the recent interest in animal personality and behavioral syndromes, there is a paucity of explanations for why distinct behavioral traits should evolve to correlate. We investigate whether such correlations across apparently distinct behavioral traits may be explained by variation in life history strategy among individual ant colonies. Life history theory predicts that the way in which individuals allocate energy towards somatic maintenance or reproduction drives several distinct traits in physiology, morphology, and energy use; it also predicts that an individual's willingness to engage in risky behaviors should depend on reproductive strategy. We use Temnothorax ants, which have been shown to exhibit 'personalities' and a syndrome that may reflect risk tolerance at the colony level. We measure colonies' relative investment in growth rate (new workers produced) compared to reproductive effort (males and queens produced). Comparing sterile worker production to reproductive alate production provides a direct measure of how colonies are investing their energy, analogous to investment in growth versus reproduction in a unitary organism. Consistently with this idea, we found that behavioral type of ant colonies was associated with their life history strategy: risk-tolerant colonies grew faster and invested more in reproduction, whereas risk-averse colonies had lower growth rate but invested relatively more in workers. This provides evidence that behavioral syndromes can be a consequence of life-history strategy variation, linking the two fields and supporting the use of an integrative approach.
Screening the TOMRES collection for combined stress tolerance in Northern European glasshouse conditions
<p>These experiments assessed varietal yield and quality in response to a combined treatment of reduced N and P application and severe water limitation (Combined stress) when grown in rockwool substrates. <br> Data was collection to assess relative NUE of varieties under treatment and control conditions as well as the physiological performance and fruit quality characteristics of varieties in order to contribute to a ranking for combined stress. </p> <p>Two trials were carried out (February - May 2019 and June - September 2019) at the Stockbridge Technology Centre in North Yorkshire, UK. </p>
Evolution of sex-specific heat stress tolerance and larval Hsp70 expression in populations of Drosophila melanogaster adapted to larval crowding
<p class="BodyA">The ability to tolerate temperature stress is an important component of adult fitness. In holometabolous insects like <i>Drosophila melanogaster,</i> adult stress resistance can be affected by growth conditions experienced during the larval stages. While evolution under crowded larval conditions is known to lead to the correlated evolution of many adult traits, its consequences on adult heat stress tolerance have not been investigated. Therefore, in the present study, we assessed the adult heat stress tolerance in populations of <i>D.</i><i> </i><i>melanogaster</i> adapted to a stressful larval crowding environment. We used replicate populations of <i>D.</i><i> </i><i>melanogaster</i>, selected for adaptation to larval crowding stress (MCUs), for more than 230 generations, and their respective controls (MBs). Larvae from selected and control populations were grown under crowded and uncrowded conditions and their adult heat shock resistance at two different temperatures was measured. Further, we compared Hsp70 expression in crowded and uncrowded larvae of both populations and also measured the Hsp70 expression after a mild-heat treatment in adults of selected and control populations. Our results showed that adaptation to larval crowding leads to the evolution of Hsp70 gene expression in larval stages and improves adult heat-stress tolerance ability in males, but not in females. </p>
Effect of gut microbiota on α-amanitin tolerance in Drosophila tripunctata
<p><span>The bacterial gut microbiota of many animals is known to be important for many physiological functions including detoxification. The selective pressures imposed on insects by exposure to toxins may also be selective pressures on their symbiotic bacteria, who thus may contribute to the mechanism of toxin tolerance for the insect. Amatoxins are a class of cyclopeptide mushroom toxins that primarily act by binding to RNA polymerase II and inhibiting transcription. Several species of mycophagous <i>Drosophila </i>are tolerant to amatoxins found in mushrooms of the genus <i>Amanita</i>, despite these toxins being lethal to most other known eukaryotes. These species can tolerate amatoxins in natural concentrations to utilize toxic mushrooms as larval hosts, but the mechanism by which these species are tolerant remains unknown. Previous data has shown that a local population of <i>D. tripunctata</i> exhibits significant genetic variation in toxin tolerance. This study assesses the potential role of the microbiome in α-amanitin tolerance in six wild-derived strains of <i>Drosophila tripunctata</i>. Normal and antibiotic-treated samples of six strains were reared on diets with and without α-amanitin, and then scored for survival from the larval stage to adulthood and for development time to pupation. Our results show that a substantial reduction in bacterial load does not influence toxin tolerance in this system, while confirming genotype and toxin-specific effects on survival are independent of the microbiome composition. Thus, we conclude that this adaptation to exploit toxic mushrooms as a host is likely intrinsic to the fly's genome and not a property of their microbiome.</span></p>
Positive genetic covariance and limited thermal tolerance constrain tropical insect responses to global warming
<p>Tropical ectotherms are particularly vulnerable to global warming because their physiologies are assumed to be adapted to narrow temperature ranges. This study explores three mechanisms potentially constraining thermal adaptation to global warming in tropical insects: 1. tradeoffs in genotypic performance at different temperatures (the jack-of-all-trades hypothesis) 2. positive genetic covariance in performance, with some genotypes performing better than others at viable temperatures (the 'winner and 'loser genotypes hypothesis) or 3. limited genetic variation as the potential result of relaxed selection and the loss of genes associated with responses to extreme temperatures (the gene decay hypothesis). We estimated changes in growth and survival rates at multiple temperatures for three tropical rain forest insect herbivores (<i>Cephaloleia</i> rolled-leaf beetles, Chrysomelidae). We reared 2746 individuals in a full-sibling experimental design, at temperatures known to be experienced by this genus of beetles in nature (<i>i.e.</i>, 10-35°C). Significant genetic covariance was positive for 16 traits, supporting the 'winner and 'loser genotypes hypothesis. Only two traits displayed negative cross-temperature performance correlations. We detected a substantial contribution of genetic variance in traits associated with size and mass (0-44%), but low heritability in plastic traits such as development time (0-6%) or survival (0-4%). Lowland insect populations will most likely decline if current temperatures increase beyond 2°C. It is concerning that local adaption is already lagging behind current temperatures. The consequences of maintaining the current global warming trajectory would be devastating for tropical insects. However, if humans can limit or slow warming, many tropical ectotherms might persist in their current locations, and potentially adapt to warmer temperatures.</p>
Data from: Tolerability and efficacy of long-term medical therapy in primary aldosteronism
<p>Introduction: Patients with primary aldosteronism (PA) have increased cardiovascular risk and studies have found that medical therapy fails to ameliorate this. This may be due to side effects and limited efficacy of medications at tolerable doses.</p> <p>Methods: We conducted a retrospective study on 201 patients with PA treated with medical therapy (spironolactone, eplerenone or amiloride) for PA from 2000-2020 at two tertiary centres. Patients were assessed for efficacy to achieve clinical and biochemical control, and for side effects.</p> <p>Results: 53.7% of patients achieved blood pressure <140/90mmHg, 44.6% achieved potassium ≥4.3mmol/L, 63.2% achieved renin >1ng/ml/hr, and only 24.6% achieved all three. Concordance of biochemical control using potassium and renin levels was 49%. 45.3% of patients experienced side effects, with 8.5% switching to another medication, 18.9% decreasing dose, and 10.0% stopping medications altogether. Risk factors for side effects were spironolactone use, dose ≥50mg, duration of treatment ≥1year, male gender and unilateral PA. Patients with unilateral PA, compared to bilateral PA, used higher median doses of spironolactone, 75mg vs 50mg, <i>P</i><0.001, but more had persistent hypokalemia, 20.5% vs 6.4%, <i>P</i>=0.007. 44 patients with unilateral PA underwent surgery after initial medical therapy, which further improved systolic and diastolic BP, from 142 to 134mmHg, <i>P</i><0.001, and from 85 to 79mmHg, <i>P</i><0.001, respectively.</p> <p>Conclusion: Dose-dependent side effects limit the efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. In patients with unilateral PA, surgery remains a better option compared to life-long medications.</p>
Table 1 Current salinity tolerant forage legume species
<p>Table 1 Current salinity tolerant forage legume species </p>
Fig. 9 in Comparative transcriptome analysis reveals the regulatory effects of acetylcholine on salt tolerance of Nicotiana benthamiana
Fig. 9. Differential expressed genes in response to CN, NaCl and NaCl + ACh.
Fig. 2 in Transcriptome profiling of two Dactylis glomerata L. cultivars with different tolerance in response to submergence stress
Fig. 2. Venn diagram of differentially expressed genes (DEGs).
Supporting data for: Heat-evolved algal symbionts enhance bleaching tolerance of adult corals without trade-off against growth
<p>Photosymbiont-enhanced coral thermotolerance</p>
Data files and R scripts for manuscript: Acute warming tolerance (CTmax) in zebrafish (Danio rerio) appears unaffected by changes in water salinity
<p>See README and R-scripts for more info.</p> <p>Update for v2: model is now fit using <em>lmerTest</em> package. Previous version erroneously used <em>lme4</em>, which does not work for using type 3 sums of squares in anova.</p> <p>Update for v3: 1) An additional term has been added to the model, including the number of minutes passed from the start of the salinity treatment until the CTmax test for each fish (for the 2 hr treatment). 2) A table including the daily salinity measurements has been added.</p> <p>Update for v4: Minor error fix in "script-preload-resources.R" using wrong filename for table-salinities.txt</p> <p>Preprint: https://www.biorxiv.org/content/10.1101/2022.08.02.502531v1</p>
Safety, Tolerability, PK, and Efficacy of CD-001 in Advanced Head & Neck Cancers
ClinicalTrials.gov study NCT07072325. IPD Sharing: NO. Countries: 0. Publications: 13.
Safety and Tolerability of TOP-N53 Applied on Digital Ulcers in Patients With Systemic Sclerosis
ClinicalTrials.gov study NCT06954597. IPD Sharing: NO. Countries: 2. Publications: 0.
A Study to Evaluate the Efficacy, Safety, and Tolerability of Tapentadol ER Compared With Placebo in Patients With Chronic, Painful Diabetic Peripheral Neuropathy
ClinicalTrials.gov study NCT01041859. IPD Sharing: Not stated. Countries: 3. Publications: 0.
Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Pain Due to Osteoarthritis Taking WHO Step III Analgesics But Showing a Lack of Tolerability.
ClinicalTrials.gov study NCT00982280. IPD Sharing: Not stated. Countries: 6. Publications: 0.
Observational Trial Tolerability and Efficacy of Resiquimod Gel in Patients Treated for Actinic Keratosis.
ClinicalTrials.gov study NCT01806961. IPD Sharing: Not stated. Countries: 2. Publications: 0.
Study of Azeliragon in Patients With Mild Alzheimer's Disease and Impaired Glucose Tolerance
ClinicalTrials.gov study NCT03980730. IPD Sharing: NO. Countries: 2. Publications: 0.
Efficacy of Oral Tolerance Induction to Raw Apple
ClinicalTrials.gov study NCT04116580. IPD Sharing: NO. Countries: 0. Publications: 9.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
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DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.