| 1. |
- Costa, Fabiano, et al.
(author)
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Acetic acid-induced pain elicits stress-, and camouflage-related responses in zebrafish: Modulatory effects of opioidergic drugs on neurobehavioral phenotypes
- 2023
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In: Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology. - 1532-0456. ; 270
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Journal article (peer-reviewed)abstract
- While pain results from the activation of nociceptors following noxious stimuli, mounting evidence links pain- and stress-related responses in mammals. In zebrafish, the activation of hypothalamic-pituitary-interrenal (HPI) axis may also regulate body pigmentation (the camouflage response). Here, we aimed to investigate a putative relationship between pain-, stress-, and camouflage-related parameters in adult zebrafish. To answer this question, we assessed whether intraperitoneal acetic acid injection can activate the HPI axis, measuring whole-body cortisol and the camouflage response as physiological endpoints in the presence or absence of morphine or naloxone, an opioid antagonist. Acetic acid induced a stereotypic circling behavior in the top of the tank, accompanied by abdominal writhing-like response, a specific phenotype that reflects local nociceptive effect. Both whole-body cortisol levels and camouflage response increased in the acetic acid group, while morphine prevented these responses, and naloxone antagonized morphine-induced effects. Moreover, we observed positive correlations between representative behavioral, physiological and skin coloration endpoints, and a “pain index” was proposed to summarize phenotypic profile of zebrafish under different pharmacological manipulations. Collectively, these findings suggest a coordinated activation of pain, camouflage- and stress-related pathways following acetic acid injection in zebrafish. Our data also support that camouflage response represents a novel and relevant biomarker for future probing pain and stress neurobiology, with a robust sensitivity to opioidergic drugs.
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| 2. |
- Da Silva, Léuson, et al.
(author)
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Detecting semantic conflicts with unit tests
- 2024
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In: Journal of Systems and Software. - 0164-1212. ; 214
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Journal article (peer-reviewed)abstract
- While modern merge techniques, such as 3-way and structured merge, can resolve textual conflicts automatically, they fail when the conflict arises not at the syntactic, but at the semantic level. Detecting such semantic conflicts requires understanding the behavior of the software, which is beyond the capabilities of most existing merge tools. Although semantic merge tools have been proposed, they are usually based on heavyweight static analyses, or need explicit specifications of program behavior. In this work, we take a different route and propose SAM (SemAntic Merge), a semantic merge tool based on the automated generation of unit tests that are used as partial specifications of the changes to be merged, and that drive the detection of unwanted behavior changes (conflicts) when merging software. To evaluate SAM's feasibility for detecting conflicts, we perform an empirical study relying on a dataset of more than 80 pairs of changes integrated to common class elements (constructors, methods, and fields) from 51 merge scenarios. We also assess how the four unit test generation tools used by SAM individually contribute to conflict identification. Our results show that SAM performs best when combining only the tests generated by Differential EvoSuite and EvoSuite, and using our proposed testability transformations (nine detected conflicts out of 29). These results reinforce previous findings about the potential of using test-case generation to detect conflicts as a method that is versatile and requires only limited deployment effort in practice.
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| 3. |
- Silva, Leuson Da, et al.
(author)
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Detecting Semantic Conflicts Via Automated Behavior Change Detection
- 2020
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In: 2020 IEEE International Conference on Software Maintenance and Evolution (ICSME).
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Conference paper (peer-reviewed)abstract
- Branching and merging are common practices in collaborative software development. They increase developer productivity by fostering teamwork, allowing developers to independently contribute to a software project. Despite such benefits, branching and merging comes at a cost-the need to merge software and to resolve merge conflicts, which often occur in practice. While modern merge techniques, such as 3-way or structured merge, can resolve many such conflicts automatically, they fail when the conflict arises not at the syntactic, but the semantic level. Detecting such conflicts requires understanding the behavior of the software, which is beyond the capabilities of most existing merge tools. As such, semantic conflicts can only be identified and fixed with significant effort and knowledge of the changes to be merged. While semantic merge tools have been proposed, they are usually heavyweight, based on static analysis, and need explicit specifications of program behavior. In this work, we take a different route and explore the automated creation of unit tests as partial specifications to detect unwanted behavior changes (conflicts) when merging software.We systematically explore the detection of semantic conflicts through unit-test generation. Relying on a ground-truth dataset of 38 software merge scenarios, which we extracted from GitHub, we manually analyzed them and investigated whether semantic conflicts exist. Next, we apply test-generation tools to study their detection rates. We propose improvements (code transformations) and study their effectiveness, as well as we qualitatively analyze the detection results and propose future improvements. For example, we analyze the generated test suites for false-negative cases to understand why the conflict was not detected. Our results evidence the feasibility of using test-case generation to detect semantic conflicts as a method that is versatile and requires only limited deployment effort in practice, as well as it does not require explicit behavior specifications.
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| 4. |
- Tomaz, Kaira C P, et al.
(author)
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Identification of potential inhibitors of casein kinase 2 alpha of Plasmodium falciparum with potent in vitro activity.
- 2023
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In: Antimicrobial Agents and Chemotherapy. - 0066-4804. ; 67:11
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Journal article (peer-reviewed)abstract
- Drug resistance to commercially available antimalarials is a major obstacle in malaria control and elimination, creating the need to find new antiparasitic compounds with novel mechanisms of action. The success of kinase inhibitors for oncological treatments has paved the way for the exploitation of protein kinases as drug targets in various diseases, including malaria. Casein kinases are ubiquitous serine/threonine kinases involved in a wide range of cellular processes such as mitotic checkpoint signaling, DNA damage response, and circadian rhythm. In Plasmodium, it is suggested that these protein kinases are essential for both asexual and sexual blood-stage parasites, reinforcing their potential as targets for multi-stage antimalarials. To identify new putative PfCK2α inhibitors, we utilized an in silico chemogenomic strategy involving virtual screening with docking simulations and quantitative structure-activity relationship predictions. Our investigation resulted in the discovery of a new quinazoline molecule (542), which exhibited potent activity against asexual blood stages and a high selectivity index (>100). Subsequently, we conducted chemical-genetic interaction analysis on yeasts with mutations in casein kinases. Our chemical-genetic interaction results are consistent with the hypothesis that 542 inhibits yeast Cka1, which has a hinge region with high similarity to PfCK2α. This finding is in agreement with our in silico results suggesting that 542 inhibits PfCK2α via hinge region interaction.
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