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From subsidies to stressors: Positively skewed ecological gradients alter biological responses to nutrients in streams.
Ecol Appl
January 2025
U.S. Geological Survey, Lower Mississippi-Gulf Water Science Center, Jackson, Mississippi, USA.
Subsidy-stress gradients offer a useful framework for understanding ecological responses to perturbation and may help inform ecological metrics in highly modified systems. Historic, region-wide shifts from bottomland hardwood forest to row crop agriculture can cause positively skewed impact gradients in alluvial plain ecoregions, resulting in tolerant organisms that typically exhibit a subsidy response (increased abundance in response to environmental stressors) shifting to a stress response (declining abundance at higher concentrations). As a result, observed biological tolerance in modified ecosystems may differ from less modified regions, creating significant challenges for detecting biological responses to restoration efforts.
View Article and Find Full Text PDFA phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.
Cancer Chemother Pharmacol
January 2025
Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.
View Article and Find Full Text PDFImproving detection of monogenic diabetes through reanalysis of GCK variants of uncertain significance.
Acta Diabetol
January 2025
Adelaide Medical School, University of Adelaide, Adelaide, Australia.
Aims: To assess the utility of reanalysing GCK variants of uncertain significance (VUS) as an intervention to improve the detection of monogenic diabetes.
Methods: We examined GCK VUS in a local cohort of individuals with suspected monogenic diabetes and re-curated each variant against the recent ClinGen GCK-specific variant classification guidelines.
Results: Variant reanalysis achieved a new 'likely pathogenic' classification (i.
Autoinducer-2 enhances the defense of against oxidative stress and DNA damage by modulation of c-di-GMP signaling via a two-component system.
mBio
January 2025
State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
As a universal language across the bacterial kingdom, the quorum sensing signal autoinducer-2 (AI-2) can coordinate many bacterial group behaviors. However, unknown AI-2 receptors in bacteria may be more than what has been discovered so far, and there are still many unknown functions for this signal waiting to be explored. Here, we have identified a membrane-bound histidine kinase of the pathogenic bacterium , AsrK, as a receptor that specifically detects AI-2 under low boron conditions.
View Article and Find Full Text PDFBI 1703880, a novel STimulator of INterferon Genes (STING) agonist, has demonstrated preclinical antitumor activity. As STING activation can upregulate programmed death ligand 1 and human leukocyte antigen in tumor cells, a combination of BI 1703880 and an anti-programmed cell death protein 1-antibody, such as ezabenlimab, may improve efficacy. This first-in-human phase Ia study (NCT05471856) is evaluating BI 1703880 plus ezabenlimab in patients with advanced solid tumors.
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