Psychiatric disorders are multifactorial conditions without clear biomarkers, influenced by genetic, environmental, and developmental factors. Understanding these disorders requires identifying specific endophenotypes that help break down their complexity. Here, we undertake an in-depth analysis of one such endophenotype, namely imbalanced approach-avoidance conflict (AAC), reviewing its significant dependency on the hippocampus.
View Article and Find Full Text PDFBackground: The study of neurons is fundamental to unraveling the complexities of the nervous system. Primary neuronal cultures from rodents have long been a cornerstone of experimental studies, yet limitations related to their non-human nature and ethical concerns have prompted the development of alternatives. In recent years, the derivation of neurons from human-induced pluripotent stem cells (hiPSCs) has emerged as a powerful option, offering a scalable source of cells for diverse applications.
View Article and Find Full Text PDFRecent branching (100 MYA) of the mammalian evolutionary tree has enhanced brain complexity and functions at the putative cost of increased emotional circuitry vulnerability. Thus, to better understand psychopathology, a burden for the modern society, novel approaches should exploit evolutionary aspects of psychiatric-relevant molecular pathways. A handful of genes is nowadays tightly associated to psychiatric disorders.
View Article and Find Full Text PDFInfarct expansion can occur after myocardial infarction (MI), which leads to adverse left ventricular (LV) remodeling and failure. An imbalance between matrix metalloproteinase (MMP) induction and tissue inhibitors of MMPs (TIMPs) can accelerate this process. Past studies have shown different biologic effects of TIMP-3, which may depend upon specific domains within the TIMP-3 molecule.
View Article and Find Full Text PDFBackground: The vascular endothelium is a novel target for the detection, management, and prevention of doxorubicin (DOX)-induced cardiotoxicity.
Objectives: The study aimed to: 1) develop a methodology by computed tomography angiography (CTA) to evaluate stress-induced changes in epicardial coronary diameter; and 2) apply this to a chronic canine model of DOX-induced cardiotoxicity to assess vascular toxicity.
Methods: To develop and validate quantitative methods, sequential retrospectively gated coronary CTAs were performed in 16 canines.
Background: Although strategies have focused on myocardial salvage/regeneration in the context of an acute coronary syndrome and a myocardial infarction (MI), interventions targeting the formed MI region and altering the course of the post-MI remodeling process have not been as well studied. This study tested the hypothesis that localized high-frequency stimulation instituted within a formed MI region using low-amplitude electrical pulses would favorably change the trajectory of changes in left ventricle geometry and function.
Methods: At 7 days following MI induction, pigs were randomized for localized high-frequency stimulation (n = 5, 240 bpm, 0.
The mechanical response of intact blood vessels to applied loads can be delineated into passive and active components using an isometric decomposition approach. Whereas the passive response is due predominantly to the extracellular matrix (ECM) proteins and amorphous ground substance, the active response depends on the presence of smooth muscle cells (SMCs) and the contractile machinery activated within those cells. To better understand determinants of active stress generation within the vascular wall, we subjected porcine common carotid arteries (CCAs) to biaxial inflation-extension testing under maximally contracted or passive SMC conditions and semiquantitatively measured two known markers of the contractile SMC phenotype: smoothelin and smooth muscle-myosin heavy chain (SM-MHC).
View Article and Find Full Text PDFJ Appl Physiol (1985)
October 2017
Cardiovascular disease, particularly the occurrence of myocardial infarction (MI), remains a leading cause of morbidity and mortality (Go et al., 127: e6-e245, 2013; Go et al. 129: e28-e292, 2014).
View Article and Find Full Text PDFFollowing myocardial infarction (MI), detrimental changes to the geometry, composition, and mechanical properties of the left ventricle (LV) are initiated in a process generally termed adverse post-MI remodeling. Cumulatively, these changes lead to a loss of LV function and are deterministic factors in the progression to heart failure. Proposed therapeutic strategies to target aberrant LV mechanics post-MI have shown potential to stabilize LV functional indices throughout the remodeling process.
View Article and Find Full Text PDFZn2+ appears to stabilize the myelin sheath but the mechanism of this effect is unknown. In a previous report we have shown that zinc binds to CNS myelin basic protein (MBP) in the presence of phosphate and this results in MBP aggregation. For this paper we used a solid phase zinc blotting assay to identify which myelin proteins bind zinc.
View Article and Find Full Text PDFWe have previously shown that CNS myelin basic protein (MBP) can be purified in the lipid-bound, native-like form by using a procedure based on myelin solubilization with detergents at pH above 7, and on the filter-like use of hydroxyapatite to separate non-adsorbed MBP from other myelin proteins. Here, we report on the isolation of MBP in the zwitterionic detergent 3-((3-cholamidopropyl)dimethylammonio)-1-propane sulfonate (CHAPS), which does not interfere at 280 nm and can be removed by dialysis. This detergent appears to improve MBP purification and to be suitable for fluorescence and reconstitution studies that can be useful to understand both structure and function of MBP in its natural environment.
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