Subsidiary cell generation in Poaceae is an outstanding example of local intercellular stimulation. An inductive stimulus emanates from the guard cell mother cells (GMCs) towards their laterally adjacent subsidiary cell mother cells (SMCs) and triggers the asymmetrical division of the latter. Indole-3-acetic acid (IAA) immunolocalization in Zea mays protoderm confirmed that the GMCs function as local sources of auxin and revealed that auxin is polarly accumulated between GMCs and SMCs in a timely-dependent manner. Besides, staining techniques showed that reactive oxygen species (ROS) exhibit a closely similar, also time-dependent, pattern of appearance suggesting ROS implication in subsidiary cell formation. This phenomenon was further investigated by using the specific NADPH-oxidase inhibitor diphenylene iodonium, the ROS scavenger N-acetyl-cysteine, menadione which leads to ROS overproduction, and H2O2. Treatments with diphenylene iodonium, N-acetyl-cysteine, and menadione specifically blocked SMC polarization and asymmetrical division. In contrast, H2O2 promoted the establishment of SMC polarity and subsequently subsidiary cell formation in "younger" protodermal areas. Surprisingly, H2O2 favored the asymmetrical division of the intervening cells of the stomatal rows leading to the creation of extra apical subsidiary cells. Moreover, H2O2 altered IAA localization, whereas synthetic auxin analogue 1-napthaleneacetic acid enhanced ROS accumulation. Combined treatments with ROS modulators along with 1-napthaleneacetic acid or 2,3,5-triiodobenzoic acid, an auxin efflux inhibitor, confirmed the crosstalk between ROS and auxin functioning during subsidiary cell generation. Collectively, our results demonstrate that ROS are critical partners of auxin during development of Z. mays stomatal complexes. The interplay between auxin and ROS seems to be spatially and temporarily regulated.
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Am J Cancer Res
December 2024
Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University Providence, RI 02903, USA.
Androgen receptor (AR) signaling is a target in prostate cancer therapy and can be treated with non-steroidal anti-androgens (NSAA) including enzalutamide, and apalutamide for patients with advanced disease. Metastatic castration-resistant prostate cancer (mCPRC) develop resistance becomes refractory to therapy limiting patient overall survival. Darolutamide is a novel next-generation androgen receptor-signaling inhibitor that is FDA approved for non-metastatic castration resistant prostate cancer (nmCRPC).
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany.
Ischemic heart disease is the leading cause of death worldwide. Reduced oxygen supply and myocardial hypoxia lead to tissue damage and impairment of the heart function. To the best of our knowledge, the primary functional effects of hypoxia in the multicellular model of living myocardial slices (LMSs) have not been investigated so far.
View Article and Find Full Text PDFLung Cancer
January 2025
Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Introduction: MET amplification (METamp) can be a de novo or acquired resistance driver; however, the definition of METamp that best captures patients who may respond to targeted therapy remains debated. We explored the genomic landscape of METamp NSCLC including degree of amplification, co-drivers, amplicon size, and outcomes to MET inhibitors.
Methods: Hybrid-capture NGS-based genomic profiling from 88,547 tissue and 12,428 liquid NSCLC samples were queried for METamp (copy number (CN) ≥ ploidy + 4, or amplification ratio (AmpRatio; [CN/sample ploidy] ≥ 3).
Crit Care Explor
January 2025
Department of Pediatrics, Johns Hopkins University, Baltimore, MD.
Objectives: Exploiting the complete blood count (CBC) with differential (CBC-diff) for early sepsis detection has practical value for emergency department (ED) care, especially for those without obvious presentations. The objective of this study was to develop the CBC Sepsis Index (CBC-SI) that incorporates monocyte distribution width (MDW) to enhance rapid sepsis screening.
Design: A retrospective observational study.
Nat Cancer
January 2025
Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).
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