Publications by authors named "M A Movsesian"
Synaptic dysfunction is an early feature in Alzheimer's disease (AD) and correlates with cognitive decline. Astrocytes are essential regulators of synapses, impacting synapse formation, maturation, elimination and function. To understand if synapse-supportive functions of astrocytes are altered in AD, we used astrocyte BacTRAP mice to generate a comprehensive dataset of hippocampal astrocyte transcriptional alterations in two mouse models of Alzheimer's pathology (APPswe/PS1dE9 and Tau P301S), characterizing sex and age-dependent changes.
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- Phosphodiesterase 3A gain-of-function mutations lead to hypertension and stroke, but surprisingly do not cause cardiac hypertrophy or heart failure in affected patients, suggesting a potential protective mechanism in the heart.* -
- Researchers used CRISPR-Cas9 models and human stem cells to analyze the effects of these mutations, observing that new mutations could enhance enzyme activity and self-assembly while preserving normal heart structure despite high blood pressure.* -
- In their experiments, cardiac responses in mutant models showed adaptive changes in calcium cycling and similarities in heart function to normal (wild-type) rats, indicating the mutations might lead to beneficial heart adaptations under certain conditions.*
We aimed to find out whether thin (≤500 μm) or normal (>500 μm, control) corneal thickness would impact efficacy and safety outcomes of small-incision lenticule extraction (SMILE). We retrospectively analyzed medical records of adult patients who had undergone SMILE. A total of 57 eyes were included in the “thin corneas” group and 180 eyes in the “control” group.
View Article and Find Full Text PDFBackground: The phosphodiesterase 3A (PDE3A) gene encodes a PDE that regulates cardiac myocyte cyclic adenosine monophosphate (cAMP) levels and myocardial contractile function. PDE3 inhibitors (PDE3i) are used for short-term treatment of refractory heart failure (HF), but do not produce uniform long-term benefit.
Objectives: The authors tested the hypothesis that drug target genetic variation could explain clinical response heterogeneity to PDE3i in HF.
We disclose the discovery and X-ray cocrystal data of potent, selective quinazoline inhibitors of PDE1. Inhibitor ( S)-3 readily attains free plasma concentrations above PDE1 IC values and has restricted brain access. The racemic compound 3 inhibits >75% of PDE hydrolytic activity in soluble samples of human myocardium, consistent with heightened PDE1 activity in this tissue.
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