Biology subjects

Philip, J.

Publications and source records attributed to Philip, J..

6 recordsLinked to original sources

bioRxiv2026

The role of animal personality in behavioural welfare diagnostics: a case study in Arctic charr (Salvelinus alpinus)

Animal personality is the expression of consistent among-individual variation in a behavioural trait across time and context. The application of this theory to behavioural research provides a valuable framework to investigate the among- and within-individual variation in behaviour. The animal personality theory is particularly relevant to understand and diagnostic fish welfare. It can be integrated within the nature-based welfare framework, which emphasizes the expression of species-specific behaviours and the maintenance of consistent behavioural patterns over time. Because behavioural trait such as boldness may be closely linked to other functional phenotypes, such associations reflect the broader concept of animal personality, whereby a behavioural trait can covary with another phenotypic trait to support an adaptive responses to environmental conditions. Although these relationships are both species and context dependent, they are consistently shaped by environmental conditions and environmental complexity tend to promote species specific behaviours and reduce maladaptive traits. Here we examined how structural environmental complexity shapes personality in Arctic charr and their covarying functional phenotypes, specifically growth rate and brain size. We propose that environmental complexity promotes alternative behavioural and functional phenotypes through multivariate phenotypic plasticity. We found that environmental complexity did not influence mean boldness between both treatments, but repeatability of boldness in the complex environment was remarkably consistent over a longer-term period, while estimates collapse after seven days in the plain treatment. Our findings are a clear evidence that environmental complexity foster stable behavioural trait expression and that a plain environment may suppress personality. Our results provide compelling evidence that behavioural structure and dynamics are embedded within patterns of behavioural variance. Although we found no support for behavioural covariation or associations with growth rate and brain size, we suggest that the animal personality framework may offer a valuable approach for diagnosing fish welfare issues through the partitioning of behavioural variance.

animal behavior and cognition↗

bioRxiv2021

Among-individual variation of risk-taking behaviour in group and solitary context is uncorrelated but independently repeatable in a juvenile Arctic charr (Salvelinus alpinus) aquaculture strain.

Behavioural traits have been shown to have implications in fish welfare and growth performances in aquaculture. If several studies have demonstrated the existence of repeatable and heritable behavioural traits (i.e., animal personality), the methodology to assess personality in fishes is often carried out in solitary context, which appears to somewhat limit their use from a selective breeding perspective because these tests are too time consuming. To address this drawback, group-based tests have been developed. In Nordic country, Arctic charr (Salvelinus alpinus) is widely used in aquaculture, but no selection effort on behavioural traits has yet been carried out. Specifically, in this study we examined if risk-taking behaviour was repeatable and correlated in group and solitary context and if the early influences of physical environment affect the among-individual variation of behavioural trait across time in order to verify whether a group risk-taking test could be used as a selective breeding tool. Here, we found that in both contexts and treatments, the risk-taking behaviour was repeatable across a short period of 6 days. However, no cross-context consistency was found between group and solitary, which indicates that Arctic charr express different behavioural trait in group and solitary.

animal behavior and cognition↗

bioRxiv2021

Cdc6 is sequentially regulated by PP2A-Cdc55, Cdc14 and Sic1 for origin licensing in S. cerevisiae

Cdc6, a subunit of the pre-replicative complex, contains multiple regulatory Cdk1 consensus sites, SP or TP motifs. In S. cerevisiae, Cdk1 phosphorylates Cdc6-T7 to recruit Cks1, the Cdk1 phospho-adaptor in S-phase, for subsequent multisite phosphorylation and protein degradation. Cdc6 accumulates in mitosis and is tightly bound by Clb2 through N-terminal phosphorylation in order to prevent premature origin licensing and degradation. It has been extensively studied how Cdc6 phosphorylation is regulated by the Cyclin-Cdk1 complex. However, a detailed mechanism on how Cdc6 phosphorylation is reversed by phosphatases has not been elucidated. Here, we show that PP2ACdc55 dephosphorylates Cdc6 N-terminal sites to release Clb2. Cdc14 dephosphorylates the C-terminal phospho-degron, leading to Cdc6 stabilization in mitosis. In addition, the Cdk1 inhibitor, Sic1, releases Clb2{middle dot}Cdk1{middle dot}Cks1 from Cdc6 to load Mcm2-7 on the chromatin upon mitotic exit. Thus, pre-RC assembly and origin licensing is promoted by the attenuation of distinct CDK-dependent Cdc6 inhibitory mechanisms.

cell biology↗

bioRxiv2020

Anti-tumor effects of an Id antagonist with no acquired resistance

Id proteins are helix-loop-helix (HLH) transcriptional regulators frequently overexpressed in cancer. Id proteins inhibit basic HLH transcription factors through protein-protein interactions, often inhibiting differentiation and sustaining proliferation. We recently identified a small-molecule, AGX51, which targets Id proteins for degradation and impairs ocular neovascularization in mouse models. Here we show that AGX51 treatment of cancer cell lines impaired cell growth and viability that results from a dramatic increase in ROS production upon Id degradation. In mouse models, AGX51 treatment suppressed breast cancer colonization in the lung, regressed the growth of paclitaxel-resistant breast tumors when combined with paclitaxel and reduced tumor burden in a model of sporadic colorectal neoplasia. Furthermore, in cells and mice, we failed to observe acquired resistance to AGX51 likely the result of the immutability of the binding pocket and efficient degradation of the Id proteins. Thus, AGX51 is a first-in-class compound that antagonizes Id proteins, shows strong anti-tumor effects and may be further developed for the management of multiple cancers.

cancer biology↗

bioRxiv2019

Oncologic Therapy Shapes the Fitness Landscape of ClonalHematopoiesis

Clonal hematopoiesis (CH) is frequent in cancer patients and associated with increased risk of therapy related myeloid neoplasms (tMN). To define the relationship between CH, oncologic therapy, and tMN progression, we studied 24,439 cancer patients. We show that previously treated patients have increased rates of CH, with enrichment of mutations in DNA Damage Response (DDR) genes (TP53, PPM1D, CHEK2). Exposure to radiation, platinum and topoisomerase II inhibitors have the strongest association with CH with evidence of dose-dependence and gene-treatment interactions. We validate these associations in serial sampling from 525 patients and show that exposure to cytotoxic and radiation therapy imparts a selective advantage specifically in hematopoietic cells with DDR mutations. In patients who progressed to tMN, the clone at CH demarcated the dominant clone at tMN diagnosis. CH mutational features predict risk of therapy-related myeloid neoplasm in solid tumor patients with clinical implications for early detection and treatment decisions.

genetics↗

bioRxiv2018

Genetic mechanisms of primary chemotherapy resistance in pediatric acute myeloid leukemia: A report from the TARGET initiative

Acute myeloid leukemias (AML) are characterized by mutations of tumor suppressor and oncogenes, involving distinct genes in adults and children. While certain mutations have been associated with the increased risk of AML relapse, the genomic landscape of primary chemotherapy resistant AML is not well defined. As part of the TARGET initiative, we performed whole-genome DNA and transcriptome (RNA and miRNA) sequencing analysis of pediatric AML with failure of induction chemotherapy. We identified at least three genetic groups of patients with induction failure, including those with NUP98 rearrangements, somatic mutations of WT1 in the absence of NUP98 mutations, and additional recurrent variants including those in KMT2C and MLLT10. Comparison of specimens before and after chemotherapy revealed distinct and invariant gene expression programs. While exhibiting overt therapy resistance, these leukemias nonetheless showed diverse forms of clonal evolution upon chemotherapy exposure. This included selection for mutant alleles of FRMD8, DHX32, PIK3R1, SHANK3, MKLN1, as well as persistence of WT1 and TP53 mutant clones, and elimination or contraction of FLT3, PTPN11, and NRAS mutant clones. These findings delineate genetic mechanisms of primary chemotherapy resistance in pediatric AML, which should inform improved approaches for its diagnosis and therapy.

cancer biology↗