Increased infarct wall thickness by a bio-inert material is insufficient to prevent negative left ventricular remodeling after myocardial infarction

Background

Several injectable materials have been shown to preserve or improve cardiac function as well as prevent or slow left ventricular (LV) remodeling post-myocardial infarction (MI). However, it is unclear as to whether it is the structural support or the bioactivity of these polymers that lead to beneficial effects. Herein, we examine how passive structural enhancement of the LV wall by an increase in wall thickness affects cardiac function post-MI using a bio-inert, non-degradable synthetic polymer in an effort to better understand the mechanisms by which injectable materials affect LV remodeling.

Methods and Results

Poly(ethylene glycol) (PEG) gels of storage modulus G′ = 0.5±0.1 kPa were injected and polymerized in situ one week after total occlusion of the left coronary artery in female Sprague Dawley rats. The animals were imaged using magnetic resonance imaging (MRI) at 7±1 day(s) post-MI as a baseline and again post-injection 49±4 days after MI. Infarct wall thickness was statistically increased in PEG gel injected vs. control animals (p<0.01). However, animals in the polymer and control groups showed decreases in cardiac function in terms of end diastolic volume, end systolic volume and ejection fraction compared to baseline (p<0.01). The cellular response to injection was also similar in both groups.

Conclusion

The results of this study demonstrate that passive structural reinforcement alone was insufficient to prevent post-MI remodeling, suggesting that bioactivity and/or cell infiltration due to degradation of injectable materials are likely playing a key role in the preservation of cardiac function, thus providing a deeper understanding of the influencing properties of biomaterials necessary to prevent post-MI negative remodeling.     

Comparing biological motion perception in two distinct human societies

Cross cultural studies have played a pivotal role in elucidating the extent to which behavioral and mental characteristics depend on specific environmental influences. Surprisingly, little field research has been carried out on a fundamentally important perceptual ability, namely the perception of biological motion. In this report, we present details of studies carried out with the help of volunteers from the Mundurucu indigene, a group of people native to Amazonian territories in Brazil. We employed standard biological motion perception tasks inspired by over 30 years of laboratory research, in which observers attempt to decipher the walking direction of point-light (PL) humans and animals. Do our effortless skills at perceiving biological activity from PL animations, as revealed in laboratory settings, generalize to people who have never before seen representational depictions of human and animal activity? The results of our studies provide a clear answer to this important, previously unanswered question. Mundurucu observers readily perceived the coherent, global shape depicted in PL walkers, and experienced the classic inversion effects that are typically found when such stimuli are turned upside down. In addition, their performance was in accord with important recent findings in the literature, in the abundant ease with which they extracted direction information from local motion invariants alone. We conclude that the effortless, veridical perception of PL biological motion is a spontaneous and universal perceptual ability, occurring both inside and outside traditional laboratory environments.     

Loop energy in DNA

The loop function ?(N), representing the statistical weight of N complementary residues in a closed ring, has been determined by analysis of high-resolution melting curves of a series of recombinant homopoly(A · T)_N inserts in pBR322 DNA, where 150 > N > 50 base pairs (bp). Loops are found more stable and therefore presumably less elastic than expected for an ideal, freely jointed chain. A value of 97 ± 2 bp is obtained for the empirical orientation-stiffness parameter D in the expression for nonideal chains, ?(N) = (N + D)^?1.7. The 10% increase in apparent stiffness over that of an ideal chain closely coincides with the extent of residual stacking in the loop. It is thus concluded that the more favorable loop energy, such as expected of smaller loops, is due to the incipient helical orientation of some residues, predisposing the loop to reclosure. A quantitative loop function is essential for the prediction and assignment of domains in DNA.     

Modeling the impact of periodic bottlenecks, unidirectional mutation, and observational error in experimental evolution

Antibiotic resistant bacteria are a constant threat in the battle against infectious diseases. One strategy for reducing their effect is to temporarily discontinue the use of certain antibiotics in the hope that in the absence of the antibiotic the resistant strains will be replaced by the sensitive strains. An experiment where this strategy is employed in vitro [5] produces data which showed a slow accumulation of sensitive mutants. Here we propose a mathematical model and statistical analysis to explain this data.The stochastic model elucidates the trend and error structure of the data. It provides a guide for developing future sampling strategies, and provides a framework for long term predictions of the effects of discontinuing specific antibiotics on the dynamics of resistant bacterial populations.This Research is part of the Initiative in Bioinformatics and Evolutionary Studies (IBEST) at the University of Idaho. Funding was provided by NSF EPSCoR EPS-0080935, NSF EPSCoR, EPS-0132626, and NIH NCRR grant NIH NCRR- 20RR016448. Paul Joyce is also funded by NSF DEB-0089756, and NSF DMS-0072198.     

Life cycle stages of the amphibian chytrid Batrachochytrium dendrobatidis

An overview of the morphology and life cycle of Batrachochytrium dendrobatidis, the cause of chytridiomycosis of amphibians, is presented. We used a range of methods to examine stages of the life cycle in culture and in frog skin, and to assess ultrastructural pathology in the skin of 2 frogs. Methods included light microscopy, transmission electron microscopy with conventional methods as well as high pressure freezing and freeze substitution, and scanning electron microscopy with critical point drying as well as examination of bulk-frozen and freeze-fractured material. Although chytridiomycosis is an emerging disease, B. dendrobatidis has adaptations that suggest it has long been evolved to live within cells in the dynamic tissue of the stratified epidermis. Sporangia developed at a rate that coincided with the maturation of the cell, and fungal discharge tubes usually opened onto the distal surface of epidermal cells of the stratum corneum. A zone of condensed, fibrillar, host cytoplasm surrounded some sporangia. Hyperkeratosis may be due to (1) a hyperplastic response that leads to an increased turnover of epidermal cells, and (2) premature keratinization and death of infected cells.     

Duration of protective antibodies and correlation with survival in Nile tilapia Oreochromis niloticus following Streptococcus agalactiae vaccination

Streptococcus agalactiae is a major piscine pathogen that causes significant morbidity and mortality among numerous species of freshwater, estuarine and marine fishes. Considering the economic importance of fishes susceptible to S. agalactiae throughout the world, an efficacious S. agalactiae vaccine was developed using an extracellular product (ECP) fraction and formalin-killed whole cells of S. agalactiae. A vaccine study was conducted by intraperitoneal (i.p.) injection in Nile tilapia Oreochromis niloticus in order to determine the duration of protection and its correlation to antibodies specific for this pathogen. After 47, 90 or 180 d post-vaccination (DPV), the fish were i.p. challenged with approximately 2.0 x 10(4) S. agalactiae colony-forming units (CFU) fish(-1) to determine the duration of protective immunity. The percent survival in control fish i.p.-injected with sterile TSB was 16,16, and 4% on 47, 90 and 180 DPV, respectively, while the percent survival for the vaccinated fish was 67, 62 and 49%, respectively. The specific mean antibody concentration of the vaccinated fish was significantly higher than that of the control fish, with significant correlation between the ELISA optical density (OD) and protection. These results indicate that the specific antibody has a correlation with protection following immunization with the S. agalactiae vaccine and that the vaccine can confer protection against S. agalactiae up to 180 DPV.     

Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases

Muscle protein synthesis requires energy and amino acids to proceed and can be stimulated by insulin under certain circumstances. We hypothesized that short-term provision of insulin and nutritional energy would stimulate muscle protein synthesis in healthy subjects only if amino acid availability did not decrease. Using stable isotope techniques, we compared the effects on muscle phenylalanine kinetics across the leg of an amino acid-lowering, high-energy (HE, n = 6, 162 +/- 20 kcal/h) hyperglycemic hyperlipidemic hyperinsulinemic clamp with systemic insulin infusion to a low-energy (LE, n = 6, 35 +/- 3 kcal/h, P < 0.05 vs. HE) euglycemic hyperinsulinemic clamp with local insulin infusion in the femoral artery. Basal blood phenylalanine concentrations and phenylalanine net balance, muscle protein breakdown, and synthesis (nmol.min(-1).100 g leg muscle(-1)) were not different between groups. During insulin infusion, femoral insulinemia increased to a similar extent between groups and blood phenylalanine concentration decreased 27 +/- 3% in the HE group but only 9 +/- 2% in the LE group (P < 0.01 HE vs. LE). Phenylalanine net balance increased in both groups, but the change was greater (P < 0.05) in the LE group. Muscle protein breakdown decreased in the HE group (58 +/- 12 to 35 +/- 7 nmol.min(-1).100 g leg muscle(-1)) and did not change in the LE group. Muscle protein synthesis was unchanged in the HE group (39 +/- 6 to 30 +/- 7 nmol.min(-1).100 g leg muscle(-1)) and increased (P < 0.05) in the LE group (41 +/- 9 to 114 +/- 26 nmol.min(-1).100 g leg muscle(-1)). We conclude that amino acid availability is an important factor in the regulation of muscle protein synthesis in response to insulin, as decreased blood amino acid concentrations override the positive effect of insulin on muscle protein synthesis even if excess energy is provided.