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Congenital heart defects affect at least 0.8% of newborn children and are a major cause of lethality prior to birth. Malformations of the arterial pole are particularly frequent. The myocardium at the base of the pulmonary trunk and aorta and the arterial tree associated with these great arteries are derived from splanchnic mesoderm of the second heart field (SHF), an important source of cardiac progenitor cells. These cells are controlled by a gene regulatory network that includes Fgf8, Fgf10 and Tbx1. Prdm1 encodes a transcriptional repressor that we show is also expressed in the SHF. In mouse embryos, mutation of Prdm1 affects branchial arch development and leads to persistent truncus arteriosus (PTA), indicative of neural crest dysfunction. Using conditional mutants, we show that this is not due to a direct function of Prdm1 in neural crest cells. Mutation of Prdm1 in the SHF does not result in PTA, but leads to arterial pole defects, characterized by mis-alignment or reduction of the aorta and pulmonary trunk, and abnormalities in the arterial tree, defects that are preceded by a reduction in outflow tract size and loss of caudal pharyngeal arch arteries. These defects are associated with a reduction in proliferation of progenitor cells in the SHF. We have investigated genetic interactions with Fgf8 and Tbx1, and show that on a Tbx1 heterozygote background, conditional Prdm1 mutants have more pronounced arterial pole defects, now including PTA. Our results identify PRDM1 as a potential modifier of phenotypic severity in TBX1 haploinsufficient DiGeorge syndrome patients.
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http://dx.doi.org/10.1093/hmg/ddu232 | DOI Listing |
Ann Surg Oncol
December 2024
1Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Hépatiques et Digestives, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.
BMC Endocr Disord
December 2024
National Hospital of Sri Lanka, Colombo, Sri Lanka.
Background: Reninoma is a rare cause of secondary hypertension, which can be cured with surgery if identified early before any target organ damage occurs. It leads to hypokalaemia and hypertension and typically responds well to treatment with renin-angiotensin-aldosterone system blockers. However, confirmation of the diagnosis and the localisation of this rare culprit lesion can be challenging.
View Article and Find Full Text PDFCardiovasc Res
December 2024
Cardiovascular Regeneration Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, 28029, Spain.
Aims: The Cardiac Conduction System (CCS) is progressively specified during development by interactions among a discrete number of Transcriptions Factors that ensure its proper patterning and the emergence of its functional properties. Meis genes encode homeodomain transcription factors (TFs) with multiple roles in mammalian development. In humans, Meis genes associate with congenital cardiac malformations and alterations of cardiac electrical activity, however the basis for these alterations has not been established.
View Article and Find Full Text PDFSurg Radiol Anat
December 2024
Radiology Department, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, Pierre Benite Cedex, 69495, France.
Purpose: The aim was to find bony landmarks of the pelvis for the origins and routes of uterine arteries, hoping to improve speed and safety of embolization procedures (leiomyoma, post-partum bleedings…).
Methods: We carried out a study based on the analysis of CT-angiographies in arterial phases of whole-body scans. Two measurements were done per artery, one from the origin of uterine arteries to a first perpendicular line passing through the lowest part of the sacroiliac joint, another one from the beginning of the parametrial segment from a second parallel line passing by the acetabular roof.
J Alzheimers Dis
December 2024
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Background: Semantic variant primary progressive aphasia (svPPA) is one of the main clinical phenotypes of frontotemporal lobar degeneration. Changes in both neuronal activity and cerebral perfusion have been observed in svPPA, suggesting a possible breakdown of neurovascular coupling (NVC).
Objective: To investigate alterations in NVC and their correlations with clinical manifestations in svPPA patients.
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