In most organisms, the whole genome is maintained throughout the life span. However, exceptions occur in some species where the genome is reduced during development through a process known as programmed DNA elimination (PDE). In the human and pig parasite Ascaris, PDE occurs during the 4 to 16 cell stages of embryogenesis, when germline chromosomes are fragmented and specific DNA sequences are reproducibly lost in all somatic cells. PDE was identified in Ascaris over 120 years ago, but little was known about its molecular details until recently. Genome sequencing revealed that approximately 1,000 germline-expressed genes are eliminated in Ascaris, suggesting PDE is a gene silencing mechanism. All germline chromosome ends are removed and remodeled during PDE. In addition, PDE increases the number of chromosomes in the somatic genome by splitting many germline chromosomes. Comparative genomics indicates that these germline chromosomes arose from fusion events. PDE separates these chromosomes at the fusion sites. These observations indicate that PDE plays a role in chromosome karyotype and evolution. Furthermore, comparative analysis of PDE in other parasitic and free-living nematodes illustrates conserved features of PDE, suggesting it has important biological significance. We summarize what is known about PDE in Ascaris and its relatives. We also discuss other potential functions, mechanisms, and the evolution of PDE in these parasites of humans and animals of veterinary importance.
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http://dx.doi.org/10.1371/journal.ppat.1011087 | DOI Listing |
Cells
January 2025
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions.
View Article and Find Full Text PDFCells
January 2025
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function.
View Article and Find Full Text PDFJ Cardiovasc Pharmacol
January 2025
Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Positive inotropic responses upon administration of milrinone, an inhibitor of the phosphodiesterase enzyme (PDE), involve a well-pronounced positive chronotropic effect. Here we tested whether milrinone evokes this chronotropic response solely by PDE inhibition or by a concerted action that involve additional pharmacological targets. Milrinone stimulated increases in heart rate were studied in right atrial preparations of guinea pig in the presence or absence of inhibitors of putative ancillary molecular pathways or ion channels: i.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
January 2025
Department of Respiratory and Critical Care Medicine, First People's Hospital of Kashi, Kashi 844000, China.
Hypersensitivity pneumonitis (HP), including pigeon breeder's lung (PBL), often progresses from acute inflammation to fibrosis, impairing lung function and limiting targeted therapeutic strategies. Mechanistic studies on PBL progression are limited by the lack of preclinical animal models and a predominant focus on patient data. This study explores the immunopathological characteristics of all stages of PBL in mice and evaluates the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) during the non-fibrotic stage.
View Article and Find Full Text PDFCureus
December 2024
Optometric - Glaucoma, Leicester Royal Infirmary, Leicester, GBR.
Colour vision defects (CVDs) can be both congenital and acquired, with acquired dyschromatopsia often associated with medication toxicity. This review explores various standardised colour vision tests used to detect these defects, including the Ishihara plate test, Farnsworth-Munsell 100 hue test, and anomaloscopes. These methods are evaluated for their effectiveness in diagnosing CVDs, particularly in acquired conditions.
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