The Q510E mutation in Shp2 perturbs heart valve development by increasing cell migration.

Tightly regulated cellular signaling is critical for correct heart valve development, but how and why signaling is dysregulated in congenital heart disease is not very well known. We focused on protein tyrosine phosphatase Shp2, because mutations in this signaling modulator frequently cause valve malformations associated with Noonan syndrome or Noonan syndrome with multiple lentigines (NSML). To model NSML-associated valve disease, we targeted overexpression of Q510E-Shp2 to mouse endocardial cushions (ECs) using a Tie2-Cre-based approach.

Proteomic mapping of proteins released during necrosis and apoptosis from cultured neonatal cardiac myocytes.

Cardiac injury induces myocyte apoptosis and necrosis, resulting in the secretion and/or release of intracellular proteins. Currently, myocardial injury can be detected by analysis of a limited number of biomarkers in blood or coronary artery perfusate. However, the complete proteomic signature of protein release from necrotic cardiac myocytes is unknown.

The sticholysin family of pore-forming toxins induces the mixing of lipids in membrane domains.

Sticholysins (Sts) I and II (StI/II) are pore-forming toxins (PFTs) produced by the Caribbean Sea anemone Stichodactyla helianthus belonging to the actinoporin family, a unique class of eukaryotic PFTs exclusively found in sea anemones. The role of lipid phase co-existence in the mechanism of the action of membranolytic proteins and peptides is not clearly understood. As for actinoporins, it has been proposed that phase separation promotes pore forming activity.

New approaches to prevent LEOPARD syndrome-associated cardiac hypertrophy by specifically targeting Shp2-dependent signaling.

In LEOPARD syndrome (LS) patients, mutations in the protein tyrosine phosphatase Shp2 cause hypertrophic cardiomyopathy. The prohypertrophic effects of mutant Shp2 are mediated downstream by hyperactivation of mammalian target of rapamycin. Our goal was to further define the signaling cascade that is essential for the underlying pathomechanism, thus expanding the list of potential future therapeutic targets.

Roles of hydrophobicity and charge distribution of cationic antimicrobial peptides in peptide-membrane interactions.

Cationic antimicrobial peptides (CAPs) occur as important innate immunity agents in many organisms, including humans, and offer a viable alternative to conventional antibiotics, as they physically disrupt the bacterial membranes, leading to membrane lysis and eventually cell death. In this work, we studied the biophysical and microbiological characteristics of designed CAPs varying in hydrophobicity levels and charge distributions by a variety of biophysical and biochemical approaches, including in-tandem atomic force microscopy, attenuated total reflection-FTIR, CD spectroscopy, and SDS-PAGE. Peptide structural properties were correlated with their membrane-disruptive abilities and antimicrobial activities.

The PTPN11 loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling.

The identification of mutations in PTPN11 (encoding the protein tyrosine phosphatase Shp2) in families with congenital heart disease has facilitated mechanistic studies of various cardiovascular defects. However, the roles of normal and mutant Shp2 in the developing heart are still poorly understood. Furthermore, it remains unclear how Shp2 loss-of-function (LOF) mutations cause LEOPARD Syndrome (also termed Noonan Syndrome with multiple lentigines), which is characterized by congenital heart defects such as pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM).

Stimulation of myofascial trigger points with ultrasound induces segmental antinociceptive effects: a randomized controlled study.

Musculoskeletal pain affects a significant proportion of the general population. The myofascial trigger point is recognized as a key factor in the pathophysiology of musculoskeletal pain. Ultrasound is commonly employed in the treatment and management of soft tissue pain and, in this study, we set out to investigate the segmental antinociceptive effect of ultrasound.