28Oct/16

Appearances Can Be Deceiving – The Problem With Genetic Knockout Mice Studies

Appearances Can Be Deceiving – The Problem With Genetic Knockout Mice Studies When scientists want to study the effect that a gene has on an organism, they perform what is called a “knockout” experiment. The knockout method is an experimental method, usually employed in mice, whereby the expression of a specific gene under study is blocked. The goal of this method is to learn about what effect the absence of the gene has on the animal. Due to the inevitable rise in the importance of genetic targeting in therapeutics, the knockout model has become a very important staple in studying the functions and endogenous expression patterns of single genes in vivo.… Read More...
26Oct/16

“A proteomic approach to altered innate and adaptive immunity in the pathogenesis of PAH” – A Synopsis

Below is a synopsis of “A proteomic approach to altered innate and adaptive immunity in the pathogenesis of PAH”, a talk by Marlene Rabinovitch (MD, Stanford) given at the Vera Moulton Wall Center for Pulmonary Vascular Disease (video below). It is one of my favorite talks so far in this series of lectures… Hypothesis: there is an abnormal immune response (both innate and adaptive) affecting pulmonary arteries that is common in all forms of PAH Altered adaptive immunity in PAH pathogenesis What if antigens produced in lung are the site for autoantibody formation and immune complex deposition directly in the lung and in the perivascular area?… Read More...
20Oct/16

“Matrix metalloproteinases and their inhibitors in pulmonary hypertension” – A Review

This past week, I delved into the arena of Matrix Metalloproteinases and their role in disease and Pulmonary Hypertension. One of the first papers that I read with regards to this is by S.S. Pullamsetti et al. entitled “Matrix metalloproteinases and their inhibitors in pulmonary hypertension”. My review and summary of this paper is below. Abbreviations: ECs = Endothelial Cells SMCs = Smooth Muscle Cells ECM = Extracellular Matrix PAH = Pulmonary Arterial Hypertension MMPs = Matrix Metalloproteinases TIMPs = Tissue Inhibitors of Matrix Metalloproteinases In PAH, complex remodeling is observed in the pulmonary vasculature that involves all components of the blood vessel.… Read More...
08Oct/16

Protein Of The Week: Αlpha2-Macroglobulin

Alpha2-macroglobulin is a large protein that is present in plasma. It is synthesized by liver cells and fibroblasts. It’s main functions are the inhibition of proteinases; for example it inhibits plasmin (thus inhibiting fibrinolysis) and thrombin (thus inhibiting coagulation). However, it technically has the ability to inhibit proteases from all catalytic classes, as well as the potential to have its inhibitory function removed (via reaction of it’s thiol ester group with any primary amine group). The main mechanism by which it inhibits proteases is by steric hindrance: when the alpha2-macroglobulin approaches a protease, the protease cleaves the vulnerable region on the alpha2-macroglobulin (called a “bait” region) thus causing the alpha2-macroglobulin to collapse onto the protease.… Read More...