The dependency of fetal left ventricular biomechanics function on myocardium helix angle configuration

The helix angle configuration of the myocardium is understood to contribute to the heart function, as finite element (FE) modeling of postnatal hearts showed that altered configurations affected cardiac function and biomechanics. However, similar investigations have not been done on the fetal heart. To address this, we performed image-based FE simulations of fetal left ventricles (LV) over a range of helix angle configurations, assuming a linear variation of helix angles from epicardium to endocardium. Results showed that helix angles have substantial influence on peak myofiber stress, cardiac stroke work, myocardial deformational burden, and spatial variability of myocardial strain. A good match between LV myocardial strains from FE simulations to those measured from 4D fetal echo images could only be obtained if the transmural variation of helix angle was generally between 110 and 130°, suggesting that this was the physiological range. Experimentally discovered helix angle configurations from the literature were found to produce high peak myofiber stress, high cardiac stroke work, and a low myocardial deformational burden, but did not coincide with configurations that would optimize these characteristics. This may suggest that the fetal development of myocyte orientations depends concurrently on several factors rather than a single factor. We further found that the shape, rather than the size of the LV, determined the manner at which helix angles influenced these characteristics, as this influence changed significantly when the LV shape was varied, but not when a heart was scaled from fetal to adult size while retaining the same shape. This may suggest that biomechanical optimality would be affected during diseases that altered the geometric shape of the LV.

     

Semaphorin 3A Binds to the Perineuronal Nets via Chondroitin Sulfate Type E Motifs in Rodent Brains

Chondroitin sulfate (CS) and the CS-rich extracellular matrix structures called perineuronal nets (PNNs) restrict plasticity and regeneration in the CNS. Plasticity is enhanced by chondroitinase ABC treatment that removes CS from its core protein in the chondroitin sulfate proteoglycans or by preventing the formation of PNNs, suggesting that chondroitin sulfate proteoglycans in the PNNs control plasticity. Recently, we have shown that semaphorin3A (Sema3A), a repulsive axon guidance molecule, localizes to the PNNs and is removed by chondroitinase ABC treatment (Vo, T., Carulli, D., Ehlert, E. M., Kwok, J. C., Dick, G., Mecollari, V., Moloney, E. B., Neufeld, G., de Winter, F., Fawcett, J. W., and Verhaagen, J. (2013) Mol. Cell. Neurosci. 56C, 186–200). Sema3A is therefore a candidate for a PNN effector in controlling plasticity. Here, we characterize the interaction of Sema3A with CS of the PNNs. Recombinant Sema3A interacts with CS type E (CS-E), and this interaction is involved in the binding of Sema3A to rat brain-derived PNN glycosaminoglycans, as demonstrated by the use of CS-E blocking antibody GD3G7. In addition, we investigate the release of endogenous Sema3A from rat brain by biochemical and enzymatic extractions. Our results confirm the interaction of Sema3A with CS-E containing glycosaminoglycans in the dense extracellular matrix of rat brain. We also demonstrate that the combination of Sema3A and PNN GAGs is a potent inhibitor of axon growth, and this inhibition is reduced by the CS-E blocking antibody. In conclusion, Sema3A binding to CS-E in the PNNs may be a mechanism whereby PNNs restrict growth and plasticity and may represent a possible point of intervention to facilitate neuronal plasticity.     

Effect of Ring‐Fusion on Miscibility and Domain Purity: Key Factors Determining the Performance of PDI‐Based Nonfullerene Organic Solar Cells

Compared to the rapid development of nonfullerene organic solar cells (OSCs) based on the state‐of‐the‐art indacenodithiophene (IDT)‐based small molecule acceptors (SMAs), the progress for perylene diimide (PDI)‐based electron acceptors has lagged behind owing to the lack of understanding on the structure–morphology–performance relationship of PDI SMAs. Given the ease of synthesis for PDIs and their high intrinsic electron mobility, it is crucial to identify key material parameters that influence the polymer:PDI blend morphology and to develop rational approaches for molecular design toward high‐performance PDI‐based SMAs. In this study, three pairs of PDI‐based SMAs with and without ring‐fusion are investigated and it is found that ring‐fusion and domain purity are the key structural and morphological factors determining the fill factors (FFs) and efficiencies of PDI‐based nonfullerene OSCs. This data shows that nonfullerene OSCs based on the ring‐fused PDI‐based SMAs exhibit much higher average domain purity and thus increased charge mobilities, which lead to enhanced FFs compared to those solar cells based on nonfused PDIs. This is explained by higher Florry Huggins interaction parameters as observed by melting point depression measurements. This study suggests that increasing repulsive molecular interactions to lower the miscibility between the polymer donor and PDI acceptor is the key to improve the FF and performance of PDI‐based devices.     

Summer co‐existence of small‐sized cyprinid and percid individuals in natural and impounded stretches of a lowland river: food niche partitioning among fishes

Due to changes of discharge regime downstream of a dam reservoir, an alluvial natural stretch of the Warta River changed to a macrophyte‐dominated ecosystem. Large patches of submersed, aquatic macrophytes appeared in summer and their effect is analysed in this study. These patches contained enriched macroinvertebrate assemblages (epiphyton and benthos) and they were refuge for both zooplankton and young fishes released from the reservoir. Despite these altered conditions in this stretch, roach Rutilus rutilus, perch Perca fluviatilis and ruffe Gymnocephalus cernua dominated, as they did in the natural backwater. Fishes were sampled every 2 weeks from June to August, together with their food resources to assess the partitioning of the diet among small individuals of the three species in both stretches (the natural and affected ones). The aim of the analysis was to answer how animal food associated with water plants was partitioned between the species. In both stretches, G. cernua were primarily benthivorous, but epiphytic fauna, zooplankton and large‐sized benthic chironomid larvae replaced lack of many large, benthic insects in the tailwater. Levins' food breath index decreased from 0·36 in the backwater to 0·29 in the tailwater. An opposite trend was observed for P. fluviatilis occurring among macrophytes. Perca fluviatilis were competitors of R. rutilus and took food not only in or on the river bed, but also in the water column. They ate zooplankton and epiphytic fauna and Levins' index increased from 0·32 to 0·44 in the tailwater. Rutilus rutilus fed on adult insects, algae and plant fragments in the natural stretch. In the tailwater, these food types were chiefly complemented by zooplankton. Despite this, the niche breadth of R. rutilus was similar at the two sites. Abundance of food associated with the macrophytes appeared to facilitate cohabitation in the abundant fish populations, but P. fluviatilis appeared to benefit the most in the altered river stretch.     

Force-dependent recruitment from myosin OFF-state increases end-systolic pressure–volume relationship in left ventricle

Biomechanics and Modeling in Mechanobiology - Finite element (FE) modeling is becoming increasingly prevalent in the world of cardiac mechanics; however, many existing FE models are...     

Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties

Background

The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential.

Methodology/Principal Finding

The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44⁺ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44⁺ cells consisted of mixed CD44⁺ and CD44⁻ cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44⁺ and CD44⁺ cells derived from CD44⁺-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44⁻ cells. Furthermore, freshly sorted CD44⁺ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44⁻ cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas.

Conclusion/Significance

Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify the role of CD44 in tumor cell renewal and cancer propagation in the in vivo environment.     

Evolution of indirect reciprocity by social information: the role of trust and reputation in evolution of altruism

The complexity of human's cooperative behavior cannot be fully explained by theories of kin selection and group selection. If reciprocal altruism is to provide an explanation for altruistic behavior, it would have to depart from direct reciprocity, which requires dyads of individuals to interact repeatedly. For indirect reciprocity to rationalize cooperation among genetically unrelated or even culturally dissimilar individuals, information about the reputation of individuals must be assessed and propagated in a population. Here, we propose a new framework for the evolution of indirect reciprocity by social information: information selectively retrieved from and propagated through dynamically evolving networks of friends and acquaintances. We show that for indirect reciprocity to be evolutionarily stable, the differential probability of trusting and helping a reputable individual over a disreputable individual, at a point in time, must exceed the cost-to-benefit ratio of the altruistic act. In other words, the benefit received by the trustworthy must out-weigh the cost of helping the untrustworthy.