The effect of the elongation of the proximal aorta on the estimation of the aortic wall distensibility

The compliance of the proximal aortic wall is a major determinant of cardiac afterload. Aortic compliance is often estimated based on cross-sectional area changes over the pulse pressure, under the assumption of a negligible longitudinal stretch during the pulse. However, the proximal aorta is subjected to significant axial stretch during cardiac contraction. In the present study, we sought to evaluate the importance of axial stretch on compliance estimation by undertaking both an in silico and an in vivo approach. In the computational analysis, we developed a 3-D finite element model of the proximal aorta and investigated the discrepancy between the actual wall compliance to the value estimated after neglecting the longitudinal stretch of the aorta. A parameter sensitivity analysis was further conducted to show how increased material stiffness and increased aortic root motion might amplify the estimation errors (discrepancies between actual and estimated distensibility ranging from − 20 to − 62%). Axial and circumferential aortic deformation during ventricular contraction was also evaluated in vivo based on MR images of the aorta of 3 healthy young volunteers. The in vivo results were in good qualitative agreement with the computational analysis (underestimation errors ranging from − 26 to − 44%, with increased errors reflecting higher aortic root displacement). Both the in silico and in vivo findings suggest that neglecting the longitudinal strain during contraction might lead to severe underestimation of local aortic compliance, particularly in the case of women who tend to have higher aortic root motion or in subjects with stiff aortas.

     

Carbon catabolite repression in <Emphasis Type="Italic">Thermoanaerobacterium saccharolyticum</Emphasis>

Background

The thermophilic anaerobe Thermoanaerobacterium saccharolyticum is capable of directly fermenting xylan and the biomass-derived sugars glucose, cellobiose, xylose, mannose, galactose and arabinose. It has been metabolically engineered and developed as a biocatalyst for the production of ethanol.

Results

We report the initial characterization of the carbon catabolite repression system in this organism. We find that sugar metabolism in T. saccharolyticum is regulated by histidine-containing protein HPr. We describe a mutation in HPr, His15Asp, that leads to derepression of less-favored carbon source utilization.

Conclusion

Co-utilization of sugars can be achieved by mutation of HPr in T. saccharolyticum. Further manipulation of CCR in this organism will be instrumental in achieving complete and rapid conversion of all available sugars to ethanol.

     

Optimization of Xylanase Production by Thermomyces Lanuginosus in Tomato Seed Meal Using Response Surface Methodology

Summary A 3² central composite experimental design was performed with the aim of optimizing xylanase production by Thermomyces lanuginosus grown on corn cobs in submerged cultures. Xylanase production was first tested on different nitrogen sources (tomato skin, tomato seed meal, corn steep liquor, meat peptone, bacto-tryptone and yeast extract). Tomato seed meal was the selected substrate to test the effect of two variables on xylanase production (corn cobs and tomato seed meal concentrations). A second-order quadratic model and a response surface method showed that the optimum condition for xylanase production was corn cobs 4.6% (w/v) and tomato seed meal 2.1% (w/v). The optimum conditions found were transferred to 7-l bioreactors, where activities as high as 1630 U/ml were obtained.     

Non-local Parabolic and Hyperbolic Models for Cell Polarisation in Heterogeneous Cancer Cell Populations

Tumours consist of heterogeneous populations of cells. The sub-populations can have different features, including cell motility, proliferation and metastatic potential. The interactions between clonal sub-populations are complex, from stable coexistence to dominant behaviours. The cell–cell interactions, i.e. attraction, repulsion and alignment, processes critical in cancer invasion and metastasis, can be influenced by the mutation of cancer cells. In this study, we develop a mathematical model describing cancer cell invasion and movement for two polarised cancer cell populations with different levels of mutation. We consider a system of non-local hyperbolic equations that incorporate cell–cell interactions in the speed and the turning behaviour of cancer cells, and take a formal parabolic limit to transform this model into a non-local parabolic model. We then investigate the possibility of aggregations to form, and perform numerical simulations for both hyperbolic and parabolic models, comparing the patterns obtained for these models.     

Spiders in the context of agricultural land abandonment in Greek Mountains: species responses,community structure and the need to preserve traditional agricultural landscapes

Agricultural land abandonment is a major conservation issue when it comes to remote Mediterranean mountainous ecosystems. Although its impact on taxa such as birds or butterflies is well known, knowledge remains poor for less studied invertebrate taxa such as spiders. We sampled ground spiders (Gnaphosidae, Liocranidae, Miturgidae and Corrinidae) in 20 randomly selected sites (1 km × 1 km; 15 pitfall traps) that well depicted a land abandonment gradient, in terms of four forest encroachment classes. Our results showed a negative effect of land abandonment on ground spider species richness and diversity (Simpson index), pinpointing that forested habitats with more than 75 % woody vegetation cover are relatively poor. We also provide evidence for the beneficial role of low intensity grazing (0.4–4 livestock units/km²) for ground spider abundance. Community analysis revealed four distinct clusters of co-occurring species, while Generalized Linear Models at cluster and species level showed the definitive role of forest encroachment, and secondarily of other environmental factors such as humidity, elevation and longitude, in regulating species distribution patterns. Conservation measures for ground spider diversity maintenance should focus on promoting traditional agricultural practices, including small-scale cultivation and mild livestock grazing in order to preserve open and semi-open rural mosaics.     

Profilin 1 is a potential biomarker for bladder cancer aggressiveness

Of the most important clinical needs for bladder cancer (BC) management is the identification of biomarkers for disease aggressiveness. Urine is a "gold mine" for biomarker discovery, nevertheless, with multiple proteins being in low amounts, urine proteomics becomes challenging. In the present study we applied a fractionation strategy of urinary proteins based on the use of immobilized metal affinity chromatography for the discovery of biomarkers for aggressive BC. Urine samples from patients with non invasive (two pools) and invasive (two pools) BC were subjected to immobilized metal affinity chromatography fractionation and eluted proteins analyzed by 1D-SDS-PAGE, band excision and liquid chromatography tandem MS. Among the identified proteins, multiple corresponded to proteins with affinity for metals and/or reported to be phosphorylated and included proteins with demonstrated association with BC such as MMP9, fibrinogen forms, and clusterin. In agreement to the immobilized metal affinity chromatography results, aminopeptidase N, profilin 1, and myeloblastin were further found to be differentially expressed in urine from patients with invasive compared with non invasive BC and benign controls, by Western blot or Elisa analysis, nevertheless exhibiting high interindividual variability. By tissue microarray analysis, profilin 1 was found to have a marked decrease of expression in the epithelial cells of the invasive (T2+) versus high risk non invasive (T1G3) tumors with occasional expression in stroma; importantly, this pattern strongly correlated with poor prognosis and increased mortality. The functional relevance of profilin 1 was investigated in the T24 BC cells where blockage of the protein by the use of antibodies resulted in decreased cell motility with concomitant decrease in actin polymerization. Collectively, our study involves the application of a fractionation method of urinary proteins and as one main result of this analysis reveals the association of profilin 1 with BC paving the way for its further investigation in BC stratification.     

The role of epigenetics in environmental and occupational carcinogenesis

Over the last few years there has been an increasing effort in identifying environmental and occupational carcinogenic agents and linking them to the incidence of a variety of human cancers. The carcinogenic process itself is multistage and rather complex involving several different mechanisms by which various carcinogenic agents exert their effect. Amongst them are epigenetic mechanisms often involving silencing of tumor suppressor genes and/or activation of proto-oncogenes, respectively. These alterations in gene expression are considered critical during carcinogenesis and have been observed in many environmental- and occupational-induced human cancers. Some of the underlying mechanisms proposed to account for such differential gene expression include alterations in DNA methylation and/or histone modifications. Throughout this article, we aim to provide a current account of our understanding on how the epigenetic pathway is involved in contributing to an altered gene expression profile during human carcinogenesis that ultimately will allow us for better cancer diagnostics and therapeutic strategies.     

Embryoid bodies from mouse stem cells express oxytocin receptor, Oct-4 and DAZL

Oxytocin is a nine amino acid peptide involved in a wide spectrum of physiological functions; predominantly those concerning reproduction and differentiation are of interest. Oxytocin receptors are expressed at early developmental stages of mammals, suggesting that oxytocin might be involved in the determination of the germ stem cell line, at the very early stages of mammalian development. In this respect, the proximate aim of the present study was to confirm and further analyze the existence of oxytocin receptors at a very early level of cell commitment, that is, the determination of germ cells derived from embryoid bodies. To achieve our purpose we have cultured mouse embryonic stem cells under conditions inducing formation of embryoid bodies. In this work, ES cells were allowed to aggregate in a novel medium, “Stefanidis medium” from day 0 to day 14 until formed EBs. RNA was isolated from EBs and using RT-PCR we showed that EBs expressed Oct-4, OTR, OT, and DAZL. To demonstrate simultaneous expression immunocytochemistry was preformed, in which EBs showed strong immunoreactivity for both, OTR and DAZL molecular markers. We found that 35% of the cells displayed OTR, using flow cytometry. In addition, this novel medium showed to increase OTR mRNA. We propose, that at least in murine induced embryoid bodies there is simultaneous expression of oxytocin receptors and germ cell markers (DAZL) in many cells (expressing Oct-4). We thus conclude that, the oxytocin might indeed be a molecule playing a leading role in germ cell determination.