Category Archives: Science

Science

MIT Tech Review Article on Stem Cell Differentiation Control

Biosingularity links today to an article in the MIT Technology Review on the state of science with regard to directing differentiation of stem cells into more specific types and tissues. This is of course an area that has been under study for a while. It’s essential to our potential ability to engineer replacement tissues. At the heart of the issue is what makes cells — which each have the entire blueprint for your body — develop into particular types, at the level of DNA transcription.  While the pathways and molecules involved have been under investigation with some fruitful results, this is a major step in that people are beginning to integrate all of the information that’s been discovered, with an aim toward total deliberate control of cell development.

Technorati Tags: , ,

Article Review: Role of ATP-Regulated Potassium Channels … [in] Ischemia by Furukawa et al.

Another long title. The whole thing is below.

Hubmed Page: Role of Cardiac ATP-Regulated Potassium Channels in Differential Responses of Endocardial and Epicardial Cells to Ischemia

This 8-page article quantifies in great detail the ATP sensitivity of ATP-regulated potassium channels, often referred to as IK(ATP). As the article shows by many references, it’s known that the epicardium of the heart is more sensitive to lack of oxygen (and therefore metabolic energy in the form of adenosine triphosophate — ATP) than then endocardium of the heart. The authors of this study first measured currents from ATP-regulated potassium channels in the presence of CN (cyanide, which blocks the generation of ATP), and then more directly pulled off patches of cell membrane with ATP-regulated potassium channels, and tested them in the presence of varying concentrations of ATP. In both cases, action potentials (the way in which cardiac cells ‘fire’ to initiate contraction and signal each other) were shortened more in the epicardial patches than in those from the endocardium. The degree to which this shortening occurred and at what concentrations is well-documented in the article.
The results of this study are clear, well-presented, and extremely useful in modeling ischemia in the heart. It’s a long read, with a ton of experimental detail, but the results are worth slogging through all of that. This fundamental article on ATP-regulated potassium channels is a must-read for anyone wanting to study ischemia and infarction in the heart.

Article Review: What can nonlinear dynamics teach us about … [tachycardia/fibrillation]? by Li et al.

I had to cut the title a bit short, because it’s a long one.

Hubmed Page: What can nonlinear dynamics teach us about the development of ventricular tachycardia/ventricular fibrillation?

This short article (3 pages) describes in a very readable way how nonlinear dynamics may be applied to understand beat-to-beat alternans of action potential duration and amplitude. While the actual methods used are not written, the concept is well-conveyed. I’ve not yet had a course in nonlinear dynamics, so some of the terminology was a bit beyond my understanding. I don’t know anything about eigenmodes, for example.

After providing a brief background of nonlinear dynamics, the authors elaborate on how they used nonlinear dynamics to develop a realistic model of calcium cycling and alternans in the canine myocardium. All-in-all, it’s not a terribly informative paper. Like many articles that mention fibrillation and tachycardia, it comes up short of actually linking the found mechanisms to clinical application and human disease. It is, however, a nice introduction to the topic, and the references look promising. If you have an interest in cardiac arrhythmias, and aren’t very familiar with this sort of analysis, I recommend you read it over and consider further study of the topic.

Article Review: Reentry in heterogeneous cardiac tissue described by the Luo-Rudy ventricular action potential model by K.H.W.J. Ten Tusscher and A.V. Panfilov

Hubmed Page: Reentry in heterogeneous cardiac tissue described by the Luo-Rudy ventricular action potential model (with abstract)
The primary focus of this article is the effect of a gradient of action potential duration (APD) on spiral wave dynamics. The authors ran several simulations of a spiral wave using the Luo-Rudy I ionic model, and tracked the drift of the spiral wave’s phase singularity with respect to a gradient of APD. As the abstract says, spiral wave drift was in the direction of longer rotation period (analogous to longer APD, in this case), which is right in line with what should be expected. Higher-frequency rotation should push the spiral wave center (phase singularity) away, regardless of the phenomenon underlying that higher frequency. The article is a medium-length read at six pages. While it seems somewhat redundant, in that every test yielded approximately the same results, this leant strong support to the conclusions of the paper — no caveats or qualifications were necessary. The conclusions of this article are important to the study of arrhythmias in regional disease, where gradients of electrophysiological disease exist along the borders between normal and diseased tissues.
The paper does not, unfortunately, delve into the details of why high-frequency rotation pushes away low-frequency rotation. A similar phenomenon was explained to me this past fall by Dr.Valentin Krinski with regard to two interacting spiral waves or periodic sources. I’m currently struggling to find the bridge — the relationship between different frequencies in different parts of the same spiral wave, and different frequencies in different spiral waves.

If you know why this is, kindly leave a comment. In the mean time I’ll be puzzling over it.