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Biology subjects

Kratz, L.

Publications and source records attributed to Kratz, L..

2 recordsLinked to original sources

Acclimatization potential in stress tolerant Caribbean corals - outcomes of a 5 year cross-shelf reciprocal transplant experiment

The identification and use of stress-tolerant coral in outplanting efforts has been proposed as a method of restoring and bolstering reef health under increasing environmental change. Prior research has focused on understanding survival in cross-reef transplantation, but evidence of long term resiliency of outplanted corals remains limited. Here, we report data at a five-year timepoint of a reciprocal transplant study of the stress-tolerant Caribbean corals Pseudodiploria strigosa and Siderastrea siderea between a nearshore and offshore site in Belize. Extreme marine heat wave conditions in August of 2024 revealed species and site-specific bleaching patterns. Through assessments of mortality, energy reserves, and chlorophyll concentrations, P. strigosa appear to be more limited in long-term acclimatization potential to the nearshore environment while S. siderea maintain acclimatization capacity displayed 17 months post transplant to nearshore. This work conveys information relevant to managers in selecting species for restoration efforts based on short-term growth and long-term resilience in native versus non-native sites, offers insight into potential mechanisms driving these trends, and takeaways on site specific management decisions for successful coral outplanting success.

ecology↗

SWELL1 channel-mediated D-2HG export promotes immune evasion and metabolic fitness in IDH-mutant gliomas

Isocitrate dehydrogenase (IDH) is the most frequently mutated metabolic enzyme in human cancers. Mutant IDH produces the oncometabolite D-2-hydroxyglutarate (D-2HG), which promotes tumorigenesis in part through epigenetic alterations. Beyond its cell-autonomous effects, tumor-derived D-2HG acts as a potent immunosuppressant that establishes an immune-cold tumor microenvironment. However, the mechanism by which D-2HG is released from tumors remains largely unknown. Here, we identify the SWELL1 (LRRC8A)/LRRC8C-containing volume-regulated anion channel (VRAC) as a principal pathway for D-2HG efflux from IDH-mutant cells. Genetic deletion of SWELL1, the essential VRAC subunit, markedly reduces D-2HG release and reverses associated immunosuppression in an orthotopic mouse model of IDH-mutant glioma. Strikingly, loss of VRAC causes intracellular accumulation of D-2HG, which paradoxically limits tumor cell proliferation by driving epigenetic remodeling and mitochondrial metabolic stress. Pharmacological inhibition of VRAC with dicumarol suppresses IDH-mutant glioma growth, enhances intratumoral T cell activation, synergizes with immune checkpoint blockade, and prolongs survival in tumor-bearing mice. In human IDH-mutant lower-grade gliomas, elevated LRRC8C expression correlates with DNA hypermethylation and an immunosuppressive tumor microenvironment (TME), and predicts poor overall survival. Together, these findings establish VRAC-mediated D-2HG export as a central mechanism regulating both immune evasion and tumor cell fitness, uncovering new therapeutic opportunities across IDH-mutant cancers.

cancer biology↗