Interface Water Assists in Dimethyl Sulfoxide Crossing and Poration in Model Bilayer.

Understanding the mechanism of transport and pore formation by a commonly used cryoprotectant, dimethyl sulfoxide (DMSO), across cell membranes is fundamentally crucial for drug delivery and cryopreservation. To shed light on the mechanism and thermodynamics of pore formation and crossing behavior of DMSO, extensive all-atom molecular dynamics simulations of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) bilayers are performed at various concentrations of DMSO at a temperature above the physiological temperature. Our results unveil that DMSO partially depletes water from the interface and positions itself between lipid heads without full dehydration. This induces a larger area per headgroup, increased disorder, and enhanced fluidity without any disintegration even at the highest DMSO concentration studied. The enhanced disorder fosters local fluctuations at the interface that nucleate dynamic and transient pores. The potential of mean force (PMF) of DMSO crossing is derived from two types of biased simulations: a single DMSO pulling using the umbrella sampling technique and a cylindrical pore formation using the recently developed chain reaction coordinate method. In both cases, DMSO crossing encounters a barrier attributed to unfavorable polar nonpolar interactions between DMSO and lipid tails. As the DMSO concentration increases, the barrier height reduces along with the faster lateral and perpendicular diffusion of DMSO suggesting favorable permeation. Our findings suggest that the energy required for pore formation decreases when water assists in the formation of DMSO pores. Although DMSO displaces water from the interface toward the far interface region without complete dehydration, the presence of interface water diminishes pore formation free energy. The existence of interface water leads to the formation of a two-dimensional percolated water-DMSO structure at the interface, which is absent otherwise. Overall, these insights into the mechanism of DMSO crossing and pore formation in the bilayer will contribute to understanding cryoprotectant behavior under supercooled conditions in the future.

Development of a hydrolase mimicking peptide amphiphile and its immobilization on silica surface for stereoselective and enhanced catalysis.

Biocatalysis is an important area of modern research and is extensively explored by various industries to attain greener methods in various applications. Supramolecular interactions of short peptides have been under the scanner for developing artificial smart materials inspired from natural systems. Peptide-based artificial enzymes have been proved to show various enzyme-like activities. Therefore, immobilization of catalytic peptides on solid surfaces can be an extremely useful breakthrough for development of cost-effective catalytic formulations. In this work, a series of peptide amphiphiles (PAs) have been systematically analyzed to find the most effective catalyst with esterase like activity. The PA, containing a catalytic triad, 'Asp(Ser)His' in a branched manner, was further immobilized onto silica nanoparticles through covalent bonding method to obtain surface coated catalytic silica nanoparticles. The heterogenous catalytic formulation not only showed enhanced esterase activity than the self-assembled PA in homogenous phase, but also exceeded the activity of natural CV lipase. The catalytic formulation showed high stereoselectivity towards chiral esters. Moreover, the catalyst remained stable at higher temperature, in presence of various denaturant and retained its activity after several catalytic cycles. The ease of separation, robust nature, reusability and high stereoselectivity of the catalyst opens up the possibility of creating new generation heterogeneous catalysts for further industrial applications.

Rare case of iatrogenic aortic valve leaflet tear following a diagnostic coronary angiogram.

We report a rare case of a 44-year-old male who underwent a diagnostic coronary angiogram following a non-ST elevation myocardial infarction complicated by an aortic valve leaflet tear requiring surgical intervention. Routine transthoracic echocardiogram demonstrated a mobile echogenic structure prolapsing into the left ventricular outflow tract. An intraoperative transesophageal echocardiogram confirmed that the structure originated from the ventricular side of left coronary cusp, causing malcoaptation between left and right coronary cusps, and subsequent moderate to severe aortic regurgitation.

An Unusual Case of Cardiac Tamponade Secondary to an Elevated Right Hemidiaphragm.

Diaphragmatic eventration in old age is a rare phenomenon. Typically, it is thought to originate as a result of failure of development of the muscles of the diaphragm. Less commonly, it can occur secondary to acquired conditions resulting from spinal cord or phrenic nerve injury and is only detected incidentally when the patient presents with dyspnea, chest infection, or cardiac compression symptoms. Herein, we report a case of right diaphragmatic paralysis in a 58-year-old man with a presentation of marked elevation of the right hemidiaphragm and ascites causing a picture compatible with cardiac tamponade.