The pleiotropic and complex gibberellin (GA) response relies on targeted proteolysis of DELLA proteins mediated by a GA-activated GIBBERELLIN-INSENSITIVE DWARF1 (GID1) receptor. The tomato () genome encodes for a single DELLA protein, PROCERA (PRO), and three receptors, SlGID1a (GID1a), GID1b1, and GID1b2, that may guide specific GA responses. In this work, clustered regularly interspaced short palindromic repeats (CRISPR) /CRISPR associated protein 9-derived mutants were generated and their effect on GA responses was studied. The triple mutant was extremely dwarf and fully insensitive to GA. Under optimal growth conditions, the three receptors function redundantly and the single mutants exhibited very mild phenotypic changes. Among the three receptors, GID1a had the strongest effects on germination and growth. Yeast two-hybrid assays suggested that GID1a has the highest affinity to PRO. Analysis of lines with a single active receptor demonstrated a unique role for GID1a in protracted response to GA that was saturated only at high doses. When the mutants were grown in the field under ambient changing environments, they showed phenotypic instability, the high redundancy was lost, and exhibited dwarfism that was strongly exacerbated by the loss of another receptor gene. These results suggest that multiple GA receptors contribute to phenotypic stability under environmental extremes.
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http://dx.doi.org/10.1105/tpc.19.00235 | DOI Listing |
Nanotoxicology
January 2025
Institute of Biotechnology, College of Natural Sciences, University of Rzeszow, Rzeszow, Poland.
Urotropine, an antibacterial agent to treat urinary tract bacterial infections, can be also considered as a repurposed drug with formaldehyde-mediated anticancer activity. Recently, we have synthesized urotropine surface modified iron oxide nanoparticles (URO@FeO NPs) with improved colloidal stability and limited cytotoxicity against human fibroblasts. In the present study, we have investigated URO@FeO NP-mediated responses in a panel of forty phenotypically different breast cancer cell lines along with three non-cancerous corresponding cell lines.
View Article and Find Full Text PDFComput Biol Med
January 2025
Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; Department of Pharmaceutical Medicine and Regulatory Science, Yonsei University, Incheon, Republic of Korea; Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon, Republic of Korea; Department of Integrative Biotechnology, Yonsei University, Incheon, Republic of Korea. Electronic address:
Background: Erlotinib is a potent first-generation epidermal growth factor receptor tyrosine kinase inhibitor. Due to its proximity to the upper limit of tolerability, dose adjustments are often necessary to manage potential adverse reactions resulting from its pharmacokinetic (PK) variability.
Methods: Population PK studies of erlotinib were identified using PubMed databases.
J Mol Graph Model
January 2025
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomtinagar Extension, Lucknow, 226028, India; Research Cell, Amity University Uttar Pradesh, Lucknow Campus, India. Electronic address:
The Acinetobacter baumannii is a member of the "ESKAPE" bacteria responsible for many serious multidrug-resistant (MDR) illnesses. This bacteria swiftly adapts to environmental cues leading to the emergence of multidrug-resistant variants, particularly in hospital/medical settings. In this work, we have demonstrated the outer membrane protein 33-36 (Omp33-36) porin as a potential therapeutic target in A.
View Article and Find Full Text PDFJ Neurol
January 2025
Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, Rome, Italy.
Objectives: To determine whether extending anti-CGRP mAb treatment beyond 3 years influences migraine course, we analyzed migraine frequency during the first month of treatment discontinuation following three 12-month treatment cycles (Ts).
Methods: This multicenter, prospective, real-world study enrolled 212 patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who completed three consecutive Ts of subcutaneous anti-CGRP mAbs. Discontinuation periods (D1, D2, D3) were defined as the first month after T1, T2, and T3, respectively.
Front Biosci (Landmark Ed)
January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
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