Biology subjects

Cunningham, T.

Publications and source records attributed to Cunningham, T..

3 recordsLinked to original sources

bioRxiv2026

Copper transport to mitochondria by SLC25A3 contributes to skeletal myoblast differentiation and is required for survival of differentiated myotubes

Differentiation of skeletal muscle is associated with increased mitochondrial biogenesis and reliance of oxidative phosphorylation (OXPHOS). The terminal enzyme complex in the electron transport chain, cytochrome c oxidase (COX), requires copper for its assembly and activity, and copper delivery to mitochondria is essential for OXPHOS. However, when mitochondrial copper becomes essential during skeletal myoblast differentiation is not known. Here, we show that genetic deficiency of the mitochondrial copper and phosphate carrier SLC25A3 induced prior to myoblast differentiation leads to the formation of smaller myotubes, but SLC25A3 deficiency induced in mature myotubes leads to cell death and detachment. Both phenotypes are recapitulated upon genetic knockdown of COX17, a critical assembly protein for both COX copper cofactors, or by chemical inhibition of COX. Importantly, myotube death caused by SLC25A3 deficiency is rescued by copper supplementation or expression of an SLC25A3 variant that transports copper but not phosphate. Taken together these data support a model wherein copper transport by SLC25A3 and copper delivery to COX is critical for survival in mature myotubes.

cell biology↗

bioRxiv2025

Control of fall armyworm with Spodoptera frugiperda multiple nucleopolyhedrovirus in sweet corn cultivated under agroecological conditions

The fall armyworm (FAW), Spodoptera frugiperda (JE Smith) is a polyphagous pest documented on more than 80 plant species. In vegetable production systems, sweet corn is their preferred host, but also infests other plants such as chilli, tomato, pumpkins, cucumber, beans and eggplant. Control strategies are commonly carried out by the use of chemical insecticides even though resistance of S. frugiperda populations to several insecticides has been reported. Last decades, have registered rapid adoption of organic and agroecological practices in horticulture, particularly those that rely on bioinputs such as biopesticides and biofertilizers. The baculovirus Spodoptera frugiperda Multiple Nucleopolyhedrovirus (SfMNPV) is a pathogenic agent for the fall armyworm and an alternative tool used for its control in sustainable pest management strategies. In this work, we evaluate two indigenous SfMNPV-based liquid formulations sprayed on sweet corn cultivated under agroecological conditions. Larvae fed with leaves treated with SfMNPV OBs showed mortality rates ranging from 55 to 68 %. Offspring from adult surviving to OBs treatments was analyzed by PCR and the results confirmed sublethal infections and vertical transmission in the fall armyworm. Corn ears harvested from each treatment were individually observed for insect presence, where the lowest rate of fall armyworm per corn ear was registered in plants treated with SfMNPV OBs. Analysis of secondary plagues in corn ears identified the sap beetle Carpophilus dimidiatus and the maize-infesting fly larvae Euxesta mazorca as the most abundant insect pests. These results show that indigenous isolates of SfMNPV produce a significant control on FAW under agroecological conditions, suggesting that the use of formulations including this virus might be a valuable tool for pest management in sustainable vegetable production systems. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/666974v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@12e8d59org.highwire.dtl.DTLVardef@1420401org.highwire.dtl.DTLVardef@11516b7org.highwire.dtl.DTLVardef@186750b_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Targeting Regnase-1 unleashes CAR T cell antitumor activity for osteosarcoma and creates a proinflammatory tumor microenvironment

Negative regulators of T cell function represent promising targets to enhance the intrinsic antitumor activity of CAR T cells against solid tumors. However, the endogenous immune ecosystem in solid tumors often represents an immunosuppressive therapeutic barrier to CAR T cell therapy, and it is currently unknown whether deletion of negative regulators in CAR T cells reshapes the endogenous immune landscape. To address this knowledge gap, we developed CAR T cells targeting B7-H3 in immune-competent osteosarcoma models and evaluated the intrinsic and extrinsic effects of deleting a potent negative regulator called Regnase-1 (Reg-1). Deletion of Reg-1 not only improved the effector function of B7-H3-CAR T cells but also endowed them with the ability to create a proinflammatory landscape characterized by an influx of IFN{gamma}-producing endogenous T cells and NK cells and a reduction of inhibitory myeloid cells, including M2 macrophages. Thus, deleting negative regulators in CAR T cells enforces a non-cell-autonomous state by creating a proinflammatory tumor microenvironment.

immunology↗