Self-fitting shape memory polymer foam inducing bone regeneration: A rabbit femoral defect study

Although tissue engineering has been attracted greatly for healing of critical-sized bone defects, great efforts for improvement are still being made in scaffold design. In particular, bone regeneration would be enhanced if a scaffold precisely matches the contour of bone defects, especially if it could be implanted into the human body conveniently and safely. In this study, polyurethane/hydroxyapatite-based shape memory polymer (SMP) foam was fabricated as a scaffold substrate to facilitate bone regeneration. The minimally invasive delivery and the self-fitting behavior of the SMP foam were systematically evaluated to demonstrate its feasibility in the treatment of bone defects in vivo. Results showed that the SMP foam could be conveniently implanted into bone defects with a compact shape. Subsequently, it self-matched the boundary of bone defects upon shape-recovery activation in vivo. Micro-computed tomography determined that bone ingrowth initiated at the periphery of the SMP foam with a constant decrease towards the inside. Successful vascularization and bone remodeling were also demonstrated by histological analysis. Thus, our results indicate that the SMP foam demonstrated great potential for bone regeneration.     

Socio-Economic Instability and the Scaling of Energy Use with Population Size

The size of the human population is relevant to the development of a sustainable world, yet the forces setting growth or declines in the human population are poorly understood. Generally, population growth rates depend on whether new individuals compete for the same energy (leading to Malthusian or density-dependent growth) or help to generate new energy (leading to exponential and super-exponential growth). It has been hypothesized that exponential and super-exponential growth in humans has resulted from carrying capacity, which is in part determined by energy availability, keeping pace with or exceeding the rate of population growth. We evaluated the relationship between energy use and population size for countries with long records of both and the world as a whole to assess whether energy yields are consistent with the idea of an increasing carrying capacity. We find that on average energy use has indeed kept pace with population size over long time periods. We also show, however, that the energy-population scaling exponent plummets during, and its temporal variability increases preceding, periods of social, political, technological, and environmental change. We suggest that efforts to increase the reliability of future energy yields may be essential for stabilizing both population growth and the global socio-economic system.     

Anti-influenza active and low toxic N-phenyl-substituted β-amidoamidines structurally related to natural antibiotic amidinomycin

A set of racemic N-phenyl-substituted β-amidoamidines hydrochlorides 4, which are structurally related to natural antiviral agent amidinomycin (1), was synthesized in four steps starting from methacryloyl anilide (5). In the final step of the synthetic route, an uncommon monoacylation of β-aminoamidine 8 at the less reactive β-phenylamino-group took place. To rationalize this result, a mechanism which involves initial acylation at the more active amidine-function followed by intramolecular acyl-group transfer to β-phenylamino-group was suggested. All three β-amidoamidines 4d–f bearing long linear aliphatic chain (from n-C₈H₁₇ to n-C₁₂H₂₅) revealed significant in vitro activity against influenza A virus (H3N2) and modest cytotoxicity. The in vitro antiviral potency of 4d,e is 6–20 times greater than that of commercial rimantadine with lower EC₅₀ values and higher therapeutic index. The non-toxic in vivo compounds 4d–f showed a beneficial protective effect in influenza A (H3N2) infected mice.     

Alpha-lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells)

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex of human alpha-lactalbumin and oleic acid (C18:1:9 cis) that kills tumor cells by an apoptosis-like mechanism. Previous studies have shown that a conformational change is required to form HAMLET from alpha-lactalbumin, and that a partially unfolded conformation is maintained in the HAMLET complex. This study examined if unfolding of alpha-lactalbumin is sufficient to induce cell death. We used the bovine alpha-lactalbumin Ca(2+) site mutant D87A, which is unable to bind Ca(2+), and thus remains partially unfolded regardless of solvent conditions. The D87A mutant protein was found to be inactive in the apoptosis assay, but could readily be converted to a HAMLET-like complex in the presence of oleic acid. BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) and D87A-BAMLET complexes were both able to kill tumor cells. This activity was independent of the Ca(2+)site, as HAMLET maintained a high affinity for Ca(2+) but D87A-BAMLET was active with no Ca(2+) bound. We conclude that partial unfolding of alpha-lactalbumin is necessary but not sufficient to trigger cell death, and that the activity of HAMLET is defined both by the protein and the lipid cofactor. Furthermore, a functional Ca(2+)-binding site is not required for conversion of alpha-lactalbumin to the active complex or to cause cell death. This suggests that the lipid cofactor stabilizes the altered fold without interfering with the Ca(2+)site.     

An examination of the effectiveness of inflation and deflation treatments in detecting within-compound learning of a taste aversion

Two conditioned taste aversion experiments with rats assessed the relative effectiveness in providing evidence of within-compound learning of different procedures that involve the initial compound presentation of two stimuli, A and X, with the unconditioned stimulus (i.e., AX+). In Experiment 1, following a single AX+ trial, groups A+ and B+ received an additional conditioning trial (i.e., inflation treatment) with A and B, respectively, whereas group A- received an extinction trial (i.e., deflation treatment) with A. The results showed a reduction in the aversion elicited by the target stimulus, X, in group A- relative to both groups A+ and B+, which did not differ. Experiment 2 further investigated the failure of group A+ to increase the aversion to X relative to control group B+ by pairing A or B with either the same unconditioned stimulus that was previously paired with AX (groups A+ and B+) or with a stronger unconditioned stimulus (groups A* and B*). The results showed increased aversion to X in group A* relative to group B*, but not in group A+ relative to group B+. These results are interpreted as indicative of extinction of the within-compound association during the treatment with A, which could likely impair the detection of within-compound learning following an inflation, but not a deflation treatment.     

Noise driven evolutionary waves

Adaptation in spatially extended populations entails the propagation of evolutionary novelties across habitat ranges. Driven by natural selection, beneficial mutations sweep through the population in a "wave of advance". The standard model for these traveling waves, due to R. Fisher and A. Kolmogorov, plays an important role in many scientific areas besides evolution, such as ecology, epidemiology, chemical kinetics, and recently even in particle physics. Here, we extend the Fisher-Kolmogorov model to account for mutations that confer an increase in the density of the population, for instance as a result of an improved metabolic efficiency. We show that these mutations invade by the action of random genetic drift, even if the mutations are slightly deleterious. The ensuing class of noise-driven waves are characterized by a wave speed that decreases with increasing population sizes, contrary to conventional Fisher-Kolmogorov waves. When a trade-off exists between density and growth rate, an evolutionary optimal population density can be predicted. Our simulations and analytical results show that genetic drift in conjunction with spatial structure promotes the economical use of limited resources. The simplicity of our model, which lacks any complex interactions between individuals, suggests that noise-induced pattern formation may arise in many complex biological systems including evolution.