The macroscopic basis for congestive heart failure is defined as conversion of a helical heart, whereby the apical loop fiber angle orientation that produces a 60% ejection fraction becomes more transverse to develop a spheric configuration. The geometric consequence is flattening of the apical loop architecture, so that the 15% shortening can produce only 30% ejection fraction. The fundamental shape change is alteration of normal relationships between the transverse basal loop and oblique apical loop, to make the apical loop become more basal through more transverse fiber orientation. These fundamental architectural changes are then used to evolve new procedures that restore a more normal, helical, ventricular architecture in ischemic and dilated cardiomyopathy. Direct intraoperative ventricular methods underlie surgical ventricular restoration or endoventricular surgical patch plasty procedures, the Batista procedure, and Pacopexy. These intraventricular objectives are then compared with external approaches without ventriculotomy (ie, reimplantation of cells, pericardial sleeve (acorn), surface radiofrequency ablation, and the myocor approaches). A survey of current direct ventricular clinical results that improve the underlying nondamaged muscle (ie, remote segment) is defined, and related to timing of procedures directed at rebuilding more normal ventricular shape before irreversible collagen and fibrosis develop. The overall intent is to convert the spheric heart into an elliptic configuration. Novel concepts are introduced to suggest an internal ventricular patch can be used as an intercavitary curtain, through covering nonscarred septal muscle (ie, normal but distended) to amplify left ventricular function through producing a more helical structure.
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http://dx.doi.org/10.1053/stcs.2001.29959 | DOI Listing |
J Chem Inf Model
January 2025
Department of Chemistry, Indian Institute of Technology, Delhi 110016, India.
Enhanced sampling (ES) simulations of biomolecular recognition, such as binding small molecules to proteins and nucleic acid targets, protein-protein association, and protein-nucleic acid interactions, have gained significant attention in the simulation community because of their ability to sample long-time scale processes. However, a key challenge in implementing collective variable (CV)-based enhanced sampling methods is the selection of appropriate CVs that can distinguish the system's metastable states and, when biased, can effectively sample these states. This challenge is particularly acute when the binding of a flexible molecule to a conformationally rich host molecule is simulated, such as the binding of a peptide to an RNA.
View Article and Find Full Text PDFIn duplex DNA, A-T and G-C form Watson-Crick base pairs, and Hoogsteen pairing only dominates upon protein binding or DNA damage. Using NMR, we show that an A-T Hoogsteen base pair previously observed in crystal structures of transposon DNA hairpins bound to TnpA protein forms in solution even in the absence of TnpA. This Hoogsteen base pair, located adjacent to a dinucleotide apical loop, exists in dynamic equilibrium with a minor Watson-Crick conformation (population ∼11% and lifetime ∼55 µs).
View Article and Find Full Text PDFFront Physiol
December 2024
Department of Internal Medicine, Hypertension and Vascular Research Division, Henry ford hospital, Detroit, MI, United States.
Purpose Of Review: The thick ascending limb (TAL) of loop of Henle is essential for NaCl, calcium and magnesium homeostasis, pH balance and for urine concentration. NKCC2 is the main transporter for NaCl reabsorption in the TAL and its regulation is very complex. There have been recent advancements toward understanding how NKCC2 is regulated by protein trafficking, protein-protein interaction, and phosphorylation/dephosphorylation.
View Article and Find Full Text PDFBMC Biol
December 2024
Department of Ribonucleoprotein Biochemistry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Zygmunta Noskowskiego 12/14, Poznan, 61-704, Poland.
Background: Vertebrates have one Dicer ortholog that generates both microRNAs (miRNAs) and small interfering RNAs (siRNAs), in contrast to the multiple Dicer-like proteins found in flies and plants. Here, we focus on the functions of the human Dicer (hDicer) helicase domain. The helicase domain of hDicer is known to recognize pre-miRNA substrates through interactions with their apical loop regions.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.
The aryl hydrocarbon receptor (AhR) and the peroxisome proliferator-activated receptor γ (PPARγ) are ligand-activated transcription factors that have in recent years been investigated for their anti-inflammatory properties for treatment of inflammatory bowel diseases (IBDs). These are globally prevalent chronic maladies of the gut that lack cost-efficient therapeutical options capable of inducing long-term remission. In the present study, we used an in vitro Transwell co-culture model composed of Caco-2 epithelial cells in the apical compartment and lipopolysaccharide-treated (LPS) THP-1 macrophages in the basolateral compartment.
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