Biology subjects

Jones, R. J.

Publications and source records attributed to Jones, R. J..

2 recordsLinked to original sources

bioRxiv2021

The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia

The identification of new molecular pathways supporting the growth of myelodysplastic syndrome (MDS) stem and progenitor cells is needed to understand clinical variation and develop targeted therapies. Within myeloid malignancies, men have worse outcomes compared to women, suggesting male sex hormone driven effects in malignant hematopoiesis. The androgen receptor promotes the expression of five granulocyte-colony factor receptor regulated genes. Among them, CCRL2 encodes an atypical chemokine receptor that regulates cytokine signaling in differentiated granulocytes but its role in myeloid malignancies is unknown. Our study revealed that CCRL2 is upregulated in stem and progenitor cells from patients with MDS and secondary acute leukemia. CCRL2 knockdown suppressed the growth and clonogenicity of MDS92 and MDS-L cells in vitro and in vivo. Moreover, CCRL2 knockdown significantly suppressed the phosphorylation of JAK2, STAT3, and STAT5 in MDS cells. CCRL2 co-precipitated with JAK2 and its suppression decreased the interaction of JAK2 with STAT proteins. Cell lines expressing JAK2V617F showed less effect of CCRL2 knockdown on growth and clonogenicity compared to those expressing wild type. However, the selective JAK2 inhibitor fedratinib potentiated the effects of CCRL2 knockdown in MDS and leukemia cells expressing both wild type JAK2 and JAK2V617F. In conclusion, our results implicate CCRL2 as a mediator of MDS and secondary acute leukemia cell growth, in part through JAK2/STAT signaling.

cancer biology↗

bioRxiv2020

Impacts of water quality on Acropora coral settlement: The relative importance of substrate quality and light

Coral larval settlement patterns are influenced by a vast array of factors; however, the relative roles of individual factors are rarely tested in isolation, leading to confusion about which are most crucial for settlement. For example, direct effects of light environment are often cited as a major determinate of settlement patterns, yet this has not been demonstrated under environmentally realistic lighting regimes in the absence of confounding factors. Here we apply programmable multispectral lights to create realistic light spectra, while removing correlating (but not obvious) factors that are common in laboratory settlement experiments. Using two common species of Acropora - key framework builders of the Great Barrier Reef - we find little evidence that light intensity or changes in the spectral profile play a substantial role in larval settlement under most environmentally realistic settings but can under more extreme or artificial settings. We alternatively hypothesise and provide evidence that chronic conditions of light and recent sediment exposures that impact benthic substrates (e.g., crustose coralline algae) preceding settlement have a greater impact, with up to 74% decrease in settlement observed on substrates with prior exposure and poor water quality conditions. Management of water quality conditions that impact the quality of benthic-settlement substrates therefore should present a priority area of focus for improving coral recruitment.

ecology↗