Biology subjects

Harding, K.

Publications and source records attributed to Harding, K..

4 recordsLinked to original sources

bioRxiv2021

Nitrogen fixation in mesoscale eddies of the North Pacific Subtropical Gyre: patterns and mechanisms

1.Mesoscale eddies have been shown to support elevated dinitrogen (N2) fixation rates (NFRs) and abundances of N2-fixing microorganisms (diazotrophs), but the mechanisms underlying these observations are not well understood. We explored relationships among NFRs and cyanobacterial diazotroph abundances in eddy pairs of opposite polarity sampled in the North Pacific Subtropical Gyre and compared our observations to seasonal trends from the Hawaii Ocean Time-series (HOT) program. Consistent with previous reports, we found that NFRs were anomalously high for this region (up to 3.7-fold above previous monthly HOT observations) in the centers of the sampled anticyclones, coinciding with elevated abundances of Crocosphaera in the summertime. We then coupled our field-based observations, together with transcriptomic analyses of nutrient stress marker genes and ecological models, to evaluate potential mechanisms controlling diazotroph abundance and activity at the mesoscale. Specifically, we evaluated the role of biological (via estimates of growth and grazing rates) and physical controls on populations of Crocosphaera, Trichodesmium, and diatom symbionts. Our results suggest that increased Crocosphaera abundances associated with summertime anticyclones resulted from the alleviation of phosphate limitation, allowing cells to grow at rates exceeding grazing losses. In contrast, distributions of larger, buoyant taxa (Trichodesmium and diatom symbionts) appeared less affected by eddy-driven biological controls. Instead, they appeared driven by physical dynamics along frontal boundaries that separate cyclonic and anticyclonic eddies. Together, the interplay of eddy-specific changes in bottom-up control, top-down control, and the physical accumulation of cells likely explains the elevated diazotroph abundances and NFRs associated with anticyclones and eddy fronts.

ecology↗

bioRxiv2021

Dichaete, a Sox2 homologue, prevents activation of cell death in multiple developmental contexts

Precisely regulated cell death plays a critical role in normal development and is controlled by the balance of pro-apoptotic and anti-apoptotic signals. In Drosophila, transcription of the clustered cell death activators grim and reaper is turned on in the developing nervous system to eliminate neural stem cells at the end of embryonic development. This transcription is activated by a pulse of the Hox gene abdominal-A. We show here that the Sox2 homologue Dichaete inhibits neural stem cell death when overexpressed, and loss of Dichaete promotes premature neural stem cell death. The anti-apoptotic activity of Dichaete opposes the pro-apoptotic factors abdominal-A, as well as the transcription factor grainyhead. The function of all three genes impinge on an enhancer that regulates the transcription of grim and reaper. Furthermore, we find that the balance between abdominal-A and Dichaete is likely to regulate the death of other cells during development, including cells in the developing midline, the developing hindgut, and in the early abdominal epidermis. Loss of Dichaete results in premature death in these tissues. This death can be rescued by the deletion of the enhancer region between grim and reaper. These data suggest that Dichaete functions to inhibit cell death activated by abdominal-A in multiple developmental contexts.

developmental biology↗

bioRxiv2020

Activation of Rab11a and endocytosis by Phosphatidylinositol 4-kinase III beta promotes oncogenic signaling in breast cancer

Endosomes are now recognized as important sites for regulating signal transduction. Here we show that the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIII{beta}) regulates both endocytic kinetics and receptor signaling in breast cancer cells. PI4KIII{beta} generates phosphatidylinositol 4-phosphate from phosphatidylinositol and is highly expressed in a subset of breast cancers. However, the molecular mechanism by which PI4KIII{beta} promotes breast cancer is unclear. We demonstrate that ectopic PI4KIII{beta} expression increases the rates of both endocytic internalization and recycling. PI4KIII{beta} deletion reduces endocytic kinetics accompanied by a concomitant decrease in activity of the Rab11a GTPase, a protein required for endocytic function. Finally, we find that PI4KIII{beta} activates IGF-IR{beta} signaling dependent on endosome function. Regulation of endocytic function by PI4KIII{beta} is independent of its kinase activity but requires interaction with the Rab11a. This suggests that PI4KIII{beta} controls endosomal kinetics and signaling by directly modulating Rab11a function. Our work suggests a novel regulatory role for PI4KIII{beta} in endosome function and plasma membrane receptor signaling.

cancer biology↗

bioRxiv2018

A Cut/cohesin axis alters the chromatin landscape to facilitate neuroblast death

Precise control of cell death in the nervous system is essential for development. Spatial and temporal factors activate the death of Drosophila neural stem cells (neuroblasts) by controlling the transcription of multiple cell death genes through a shared enhancer, enh1. The activity of enh1 is controlled by abdominalA and Notch, but additional inputs are needed for proper specificity. Here we show that the Cut DNA binding protein is required for neuroblast death, acting downstream of enh1. In the nervous system, Cut promotes an open chromatin conformation in the cell death gene locus, allowing cell death gene expression in response to abdominalA. We demonstrate a temporal increase in global H3K27me3 levels in neuroblasts, which is enhanced by cut knockdown. Furthermore, cut regulates the expression of the cohesin subunit Stromalin in the nervous system. The cohesin components Stromalin and NippedB are required for neuroblast death, and knockdown of Stromalin increases repressive histone modifications in neuroblasts. Thus Cut and cohesin regulate apoptosis in the developing nervous system by altering the chromatin landscape.\n\nSummary statementCut regulates the programmed death of neural stem cells by altering cohesin levels and promoting a more open chromatin conformation to allow cell death gene expression.

developmental biology↗