Block and inactivation of sodium channels in nerve by amino acid derivatives. II. Dependence on temperature and drug concentration

The interaction of n-propylguanidinium (nPG) with sodium channels has been further characterized. From experiments at varying temperatures, the Q10 for the sodium current decay time constant in the two [Na+] gradients is 2.6–2.9 independent of drug. Testing several nPG concentrations we find that peak sodium current declines sharply with [nPG] at all levels, but the decay time constant approaches an asymptote above 4 mM. No "hooks" in sodium tail currents are seen. If the sodium current is allowed to decay completely before repolarization no tail current is observed. We have developed a kinetic model in which nPG acts at a single site within the sodium channel. Reaction of nPG with its receptor requires two steps. Fitting the temperature data shows that the first step involves diffusion of the drug to the site and close association with it. The second step may include molecular reorganization of the complex. The rate constants for the reaction are all simple exponential functions of voltage. Using them, the model successfully predicts decay time constants and peak currents, and their dependence on potential, [Na+] gradient, temperature, and nPG concentration. The results are consistent with the idea that an arginine residue may be closely associated with inactivation

Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss

Volumetric muscle loss (VML) is associated with loss of skeletal muscle function, and current treatments show limited efficacy. Here we show that bioconstructs suffused with genetically-labelled muscle stem cells (MuSCs) and other muscle resident cells (MRCs) are effective to treat VML injuries in mice. Imaging of bioconstructs implanted in damaged muscles indicates MuSCs survival and growth, and ex vivo analyses show force restoration of treated muscles. Histological analysis highlights myofibre formation, neovascularisation, but insufficient innervation. Both innervation and in vivo force production are enhanced when implantation of bioconstructs is followed by an exercise regimen. Significant improvements are also observed when bioconstructs are used to treat chronic VML injury models. Finally, we demonstrate that bioconstructs made with human MuSCs and MRCs can generate functional muscle tissue in our VML model. These data suggest that stem cell-based therapies aimed to engineer tissue in vivo may be effective to treat acute and chronic VML

The Ursinus Weekly, October 10, 1969

Seven join, six leave Ursinus faculty • UC and 500 colleges schedule Vietnam moratorium Wednesday; Classes not officially cancelled • William D. Reimert dies, Ursinus Board President • Dr. E. Lewis\u27 math textbook aids Ursinus blind students • Pre-Med convention • Dean Harris weds Bryn Mawr man • Editorial: A very good year • Focus: Mike Stoner in exile • Compulsory convocation: Its validity and purpose • New view of Ursinus • Dr. Rice endorses Vietnam moratorium • Kitchen cynic: Suppose U.C. had mandatory convocations • Perspectives • To eat or not to eat • Board names new members • Spotlight: Mr. Jones, cook • Centennial plans • Opinion: Suggestions for revision of the school calendar • Weaver raps • Faculty portrait: Mrs. Lucas • Woodstock vs. Ursinus • Essay on the new age • Building plans • Freshman class • Harriers extend streak to 26 • Shuman, Mangan potential greats • Flying Dutchmen edge Bears on late T.D. • Ursinus drops grid opener to Diplomats • Registration system analyzed • Lack of needed funds signals impending collapse of agency • Astronaut Scott Carpenter opens Fall Forum series • Ursinus accounting students rank first twice, and secondhttps://digitalcommons.ursinus.edu/weekly/1149/thumbnail.jp

Adding a Little Reality to Building Ontologies for Biology

BACKGROUND: Many areas of biology are open to mathematical and computational modelling. The application of discrete, logical formalisms defines the field of biomedical ontologies. Ontologies have been put to many uses in bioinformatics. The most widespread is for description of entities about which data have been collected, allowing integration and analysis across multiple resources. There are now over 60 ontologies in active use, increasingly developed as large, international collaborations. There are, however, many opinions on how ontologies should be authored; that is, what is appropriate for representation. Recently, a common opinion has been the "realist" approach that places restrictions upon the style of modelling considered to be appropriate. METHODOLOGY/PRINCIPAL FINDINGS: Here, we use a number of case studies for describing the results of biological experiments. We investigate the ways in which these could be represented using both realist and non-realist approaches; we consider the limitations and advantages of each of these models. CONCLUSIONS/SIGNIFICANCE: From our analysis, we conclude that while realist principles may enable straight-forward modelling for some topics, there are crucial aspects of science and the phenomena it studies that do not fit into this approach; realism appears to be over-simplistic which, perversely, results in overly complex ontological models. We suggest that it is impossible to avoid compromise in modelling ontology; a clearer understanding of these compromises will better enable appropriate modelling, fulfilling the many needs for discrete mathematical models within computational biology

Life-course socioeconomic positions and subclinical atherosclerosis in the multi-ethnic study of atherosclerosis

A major limitation of past work on the social patterning of atherosclerosis has been the reliance on measures of neighborhood or individual-level socioeconomic position (SEP) assessed at a single point in time in adulthood. Risk of chronic disease is thought to accumulate throughout the life-course, so the use of a measure for a single point in time may result in inaccurate estimates of the social patterning of subclinical disease. Using data from the US Multi-Ethnic Study of Atherosclerosis (MESA), we examined the relation between childhood SEP [CSEP] (father or caretaker's education), adulthood SEP [ASEP] (a summary score of income, education, and wealth), and 20-year average exposure to neighborhood poverty [NSEP] (residential addresses geocoded and linked to census data) and the prevalence of subclinical atherosclerosis, as assessed by common carotid intimal-medial thickness (IMT) in mid to late adulthood. Participants were 45-84 years of age at baseline and were sampled from six study sites in the United States. After adjustment for age, CSEP and ASEP were both inversely and independently associated with IMT in men. All three indicators CSEP, ASEP, and NSEP were inversely and independently associated with IMT in women. Associations were somewhat reduced after adjustment for cardiovascular risk factors, suggesting that these factors may play a mediating role. There was evidence of heterogeneity in effects of NSEP by gender, and in the effects of ASEP and NSEP by race/ethnicity. Our results contribute to the growing body of work that shows that SEP at multiple points in the life-course, and at the individual and neighborhood level, contributes to the development of atherosclerosis.http://deepblue.lib.umich.edu/bitstream/2027.42/61830/1/Lifecourse socioeconomic positions and subclinical atherosclerosis in the multi-ethnic study of atherosclerosis.pd