The Mediator (MED) complex plays a key role in the recruitment and assembly of the transcription machinery for the control of gene expression. Here, we report on the role of MEDIATOR18 (MED18) subunit in root development, auxin signaling and meristem cell viability in Arabidopsis thaliana seedlings. Loss-of-function mutations in MED18 reduce primary root growth, but increase lateral root formation and root hair development. This phenotype correlates with alterations in cell division and elongation likely caused by an increased auxin response and transport at the root tip, as evidenced by DR5:GFP, pPIN1::PIN1-GFP, pPIN2::PIN2-GFP and pPIN3::PIN3-GFP auxin-related gene expression. Noteworthy, med18 seedlings manifest cell death in the root meristem, which exacerbates with age and/or exposition to DNA-damaging agents, and display high expression of the cell regeneration factor ERF115. Cell death in the root tip was reduced in med18 seedlings grown in darkness, but remained when only the shoot was exposed to light, suggesting that MED18 acts to protect root meristem cells from local cell death, and/or in response to root-acting signal(s) emitted by the shoot in response to light stimuli. These data point to MED18 as an important component for auxin-regulated root development, cell death and cell regeneration in root meristems.
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http://dx.doi.org/10.1111/tpj.14114 | DOI Listing |
Cell Death Differ
December 2024
Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, D.C., USA.
Germline inactivating mutations of the SLC25A1 gene contribute to various human disorders, including Velocardiofacial (VCFS), DiGeorge (DGS) syndromes and combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic disease characterized by the accumulation of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 loss leads to these syndromes remain largely unclear. Here, we describe a mouse model of SLC25A1 deficiency that mimics human VCFS/DGS and D/L-2HGA.
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December 2024
School of Medicine, Yichun University, Yichun, 336000, China.
Iron oxide nanoparticles (IONPs) have the potential to be utilized in a multitude of fields, including biomedicine. Consequently, the potential health risks associated with their use must be carefully considered. Most biosafety evaluations of IONPs have focused on examining the impact of the material's distinctive physicochemical attributes.
View Article and Find Full Text PDFSci Rep
December 2024
School of Basic Medicine, Dali University, Dali, 671003, Yunnan, China.
Resolvin D1 (RvD1) is an endogenous anti-inflammatory mediator that modulates the inflammatory response and promotes inflammation resolution. RvD1 has demonstrated neuroprotective effects in various central nervous system contexts; however, its role in the pathophysiological processes of intracerebral hemorrhage (ICH) and the potential protective mechanisms when combined with exercise rehabilitation remain unclear. A mouse model of ICH was established using collagenase, and treatment with RvD1 combined with three weeks of exercise rehabilitation significantly improved neurological deficits, muscle strength, learning, and memory in ICH mice while reducing anxiety-like behavior.
View Article and Find Full Text PDFProstate Cancer Prostatic Dis
December 2024
Department of Radiation Oncology, Peking University First Hospital, 100034, Beijing, China.
Background: Metastatic prostate cancer (PCa) has much lower survival and ultimately develops castration resistance, which expects novel targets and therapeutic approaches. As a result of iron-dependent lipid peroxidation, ferroptosis triggers programmed cell death and has been associated with castration-resistant prostate cancer (CRPC).
Subjects: To better understand how ferroptosis can be used to treat CRPC, we reviewed the following: First, ferroptosis mechanisms and characteristics.
Sci Rep
December 2024
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Despite decades of improvements in cytotoxic therapy, the current standard of care for locally advanced pancreatic cancer (LAPC) provides, on average, only a few months of survival benefit. Stereotactic Body Radiation Therapy (SBRT), a technique that accurately delivers high doses of radiation to tumors in fewer fractions, has emerged as a promising therapy to improve local control of LAPC; however, its effects on the tumor microenvironment and hypoxia remain poorly understood. To explore how SBRT affects pancreatic tumors, we combined an orthotopic mouse model of pancreatic cancer with an intravital microscopy platform to visualize changes to the in vivo tumor microenvironment in real-time.
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