Coordination between cell differentiation and proliferation during development requires the balance between asymmetric and symmetric modes of cell division. However, the cellular intrinsic cue underlying the choice between these two division modes remains elusive. Here, we show evidence in Caenorhabditis elegans that the invariable lineage of the division modes is specified by the balance between antagonizing complexes of partitioning-defective (PAR) proteins. By uncoupling unequal inheritance of PAR proteins from that of fate determinants during cell division, we demonstrate that changes in the balance between PAR-2 and PAR-6 can be sufficient to re-program the division modes from symmetric to asymmetric and vice versa in two daughter cells. The division mode adopted occurs independently of asymmetry in cytoplasmic fate determinants, cell-size asymmetry, and cell-cycle asynchrony between sister cells. We propose that the balance between PAR proteins represents an intrinsic self-organizing cue for the specification of the two division modes during development.
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http://dx.doi.org/10.1016/j.celrep.2021.109326 | DOI Listing |
J Chem Theory Comput
January 2025
Exscientia, Schrödinger Building, Oxford Science Park, Oxford OX4 4GE, U.K.
The development of machine-learning (ML) potentials offers significant accuracy improvements compared to molecular mechanics (MM) because of the inclusion of quantum-mechanical effects in molecular interactions. However, ML simulations are several times more computationally demanding than MM simulations, so there is a trade-off between speed and accuracy. One possible compromise are hybrid machine learning/molecular mechanics (ML/MM) approaches with mechanical embedding that treat the intramolecular interactions of the ligand at the ML level and the protein-ligand interactions at the MM level.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Texas A&M Health Science Center, Bryan, TX, USA.
Background: Traumatic brain injury (TBI) is a serious societal concern and is considered a major risk factor for the development of Alzheimer's disease (AD) and related dementias. Identifying shared pathological mediators that contribute to the progression of AD following TBI may allow therapeutic targeting to reduce the likelihood of developing AD following TBI. Cerebrovascular dysfunction is present in both AD and TBI, and thrombin has been implicated as a mediator of cerebrovascular dysfunction and inflammation.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
State Key Laboratory of Grassland Agro-Ecosystems, National Demonstration Center for Experimental Grassland Science Education, College of Pastoral Agricultural Science and Technology, Lanzhou University, Lanzhou 730020, China. Electronic address:
Global warming and extremely high temperatures affect insect survival and distribution. In this study, we characterized the gene expression profiles of red (PAR) and green (PAG) morphs of the pea aphid (Acyrthosiphon pisum) at three high temperatures (30 °C, 36 °C, and 38 °C) and three treatment durations (6 h, 12 h, and 24 h) by high-throughput sequencing. Both PAR and PAG increased the number of significantly differentially expressed genes as temperature and treatment duration increased, particularly for genes associated with stress resistance, lipid metabolism, cuticular protein expression, and the initiation of various regulatory mechanisms.
View Article and Find Full Text PDFCardiovasc Ther
January 2025
Institute of Medicine, Hubei Key Laboratory of Diabetes, Hubei University of Science and Technology, Xianning, China.
Objective: We investigated the effects of resveratrol (Res) and MCC950 on the pyroptosis of vascular smooth muscle cells (VSMCs) and the potential pathway.
Methods And Results: Compared with the control (Con) group, the atherosclerosis (AS) group showed calcified nodules, which suggested that the calcification medium induced the calcification of VSMCs. VSMCs showed proliferative activity and significantly attenuated calcification under treatment with 10 mol/L Res.
Sci Rep
December 2024
Department of Epidemiology and Environmental Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
This study aimed to investigate the relationship between allergen-specific immunoglobulin E (IgE) sensitization and allergic rhinitis (AR) symptoms in school-aged children in Japan and to understand the current severity of AR symptoms and the quality of life (QOL) among children with AR. We analyzed data from 8-year-old children who participated in the Yamanashi Adjunct Study of the Japan Environment and Children's Study, focusing on those with complete information on specific IgE levels and AR (1229 for perennial AR [PAR] and 1196 for seasonal AR [SAR]). Sensitization was determined when allergen-specific IgE levels were class 2 (0.
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