Intima-Media Thickness Does Not Differ between Two Common Carotid Artery Segments in Children

Carotid intima-media thickness (cIMT) is a surrogate marker of early atherosclerotic changes in children. cIMT-studies are hard to compare, due to variations in ultrasound protocols, especially regarding the common carotid artery (CCA) segment measured in relation to the bulb. This study’s purpose was therefore to compare two distinct CCA segments in children, to see if cIMT values differ substantially according to the site of measurement. cIMT was assessed after power calculation in 30 children (15 girls) aged 8–17, using B-Mode ultrasound (5–13 MHz) at two CCA locations. The first measurement was performed over a distance of 1 cm immediately after the bulb (A), the second 1cm proximal the bulb (B) over the same distance of 1cm length. Means of end-diastolic far wall cIMT were compared between measurement A and B. cIMT in 30 participants was 0.51±0.06 mm for measurement A and 0.51±0.05 mm for measurement B. Results did not differ significantly (p = .947) over a distance of 2 cm after the bulb. According to our results, studies measuring CCA IMT within the first 2 cm, either close to the bulb or further proximal, can be compared. This will improve interpretation of data and application of reference values.     

A Three-Dimensional Skeletal Reconstruction of the Stem Amniote Orobates pabsti (Diadectidae): Analyses of Body Mass,Centre of Mass Position,and Joint Mobility

Orobates pabsti, a basal diadectid from the lower Permian, is a key fossil for the understanding of early amniote evolution. Quantitative analysis of anatomical information suffers from fragmentation of fossil bones, plastic deformation due to diagenetic processes and fragile preservation within surrounding rock matrix, preventing further biomechanical investigation. Here we describe the steps taken to digitally reconstruct MNG 10181, the holotype specimen of Orobates pabsti, and subsequently use the digital reconstruction to assess body mass, position of the centre of mass in individual segments as well as the whole animal, and study joint mobility in the shoulder and hip joints. The shape of most fossil bone fragments could be recovered from micro-focus computed tomography scans. This also revealed structures that were hitherto hidden within the rock matrix. However, parts of the axial skeleton had to be modelled using relevant isolated bones from the same locality as templates. Based on the digital fossil, mass of MNG 10181 was estimated using a model of body shape that was varied within a plausible range to account for uncertainties of the dimension. In the mean estimate model the specimen had an estimated mass of circa 4 kg. Varying of the mass distribution amongst body segments further revealed that Orobates carried most of its weight on the hind limbs. Mostly unrestricted joint morphology further suggested that MNG 10181 was able to effectively generate propulsion with the pelvic limbs. The digital reconstruction is made available for future biomechanical studies.     

Morphological gradients in the starling basilar papilla

The starling cochlea was studied with TEM at four locations along the basilar papilla to investigate gradients in morphological features over the papilla's length and width. Hair cell shape changes continuously from neural to abneural and from basal to apical. Unlike the situation in mammals, there are no distinct populations of hair cells; the previously described types (tall hair cells and short hair cells) are merely extremes in a continuum. Contacts between THC are a normal feature. Except at the base of the papilla, SHC have very large cuticular plates, suggesting a micromechanical function for these cells. In contrast to the THC, the SHC normally completely lack afferent innervation; this indicates that their function is restricted to within the basilar papilla itself. © 1992 Wiley-Liss, Inc.     

Glioma IL13Rα2 Is Associated with Mesenchymal Signature Gene Expression and Poor Patient Prognosis

A major challenge for successful immunotherapy against glioma is the identification and characterization of validated targets. We have taken a bioinformatics approach towards understanding the biological context of IL-13 receptor α2 (IL13Rα2) expression in brain tumors, and its functional significance for patient survival. Querying multiple gene expression databases, we show that IL13Rα2 expression increases with glioma malignancy grade, and expression for high-grade tumors is bimodal, with approximately 58% of WHO grade IV gliomas over-expressing this receptor. By several measures, IL13Rα2 expression in patient samples and low-passage primary glioma lines most consistently correlates with the expression of signature genes defining mesenchymal subclass tumors and negatively correlates with proneural signature genes as defined by two studies. Positive associations were also noted with proliferative signature genes, whereas no consistent associations were found with either classical or neural signature genes. Probing the potential functional consequences of this mesenchymal association through IPA analysis suggests that IL13Rα2 expression is associated with activation of proinflammatory and immune pathways characteristic of mesenchymal subclass tumors. In addition, survival analyses indicate that IL13Rα2 over-expression is associated with poor patient prognosis, a single gene correlation ranking IL13Rα2 in the top ~1% of total gene expression probes with regard to survival association with WHO IV gliomas. This study better defines the functional consequences of IL13Rα2 expression by demonstrating association with mesenchymal signature gene expression and poor patient prognosis. It thus highlights the utility of IL13Rα2 as a therapeutic target, and helps define patient populations most likely to respond to immunotherapy in present and future clinical trials.     

Seasonal Changes in the Pattern of Assimilatory Enzymes and of Proteolytic Activities in Leaves of Juvenile Ivy

Ivy growing under natural conditions is an interesting plantto study the influence of external (e.g. temperature, light)and internal (e.g. source/sink relations) factors on leaf metabolism.Leaves of this evergreen plant are subject several times toseasonal changes. The contents of selected assimilatory enzymeswere well conserved throughout the winter indicating that ivyleaves are probably able to make use of short periods with highertemperatures and to immediately restart growth in spring. Totalproteins and carbohydrates increased considerably between Februaryand May before the emergence of the new leaf generation. Theincrease in the content of non-structural carbohydrates wasdue to the accumulation of starch, while soluble sugars peakedin winter and decreased in spring. From May onwards, the assimilateswere retranslocated to the emerging young plant parts. Markedseasonal changes in the peptide hydrolase pattern were observed.All exo- and endopeptidases investigated were minimal duringsummer suggesting that the net protein remobilization from olderleaves was not based on an increase in the level of these majorpeptide hydrolases. Source/sink interactions on a whole plantlevel seem to be decisive in the regulation of seasonal changesin the pattern of assimilatory enzymes and of proteolytic activities.Since ivy leaves remain active for several years, the changesmust be reversible and occur repeatedly during the life-spanof a particular leaf.Copyright 1994, 1999 Academic Press Hedera helix L., ivy, peptide hydrolase, assimilatory enzyme, low temperatures, retranslocation     

Preadapted for invasiveness: do species traits or their plastic response to shading differ between invasive and non‐invasive plant species in their native range?

Aim Species capable of vigorous growth under a wide range of environmental conditions should have a higher chance of becoming invasive after introduction into new regions. High performance across environments can be achieved either by constitutively expressed traits that allow for high resource uptake under different environmental conditions or by adaptive plasticity of traits. Here we test whether invasive and non‐invasive species differ in presumably adaptive plasticity. Location Europe (for native species); the rest of the world and North America in particular (for alien species). Methods We selected 14 congeneric pairs of European herbaceous species that have all been introduced elsewhere. One species of each pair is highly invasive elsewhere in the world, particularly so in North America, whereas the other species has not become invasive or has spread only to a limited degree. We grew native plant material of the 28 species under shaded and non‐shaded conditions in a common garden experiment, and measured biomass production and morphological traits that are frequently related to shade tolerance and avoidance. Results Invasive species had higher shoot–root ratios, tended to have longer leaf‐blades, and produced more biomass than congeneric non‐invasive species both under shaded and non‐shaded conditions. Plants responded to shading by increasing shoot–root ratios and specific leaf area. Surprisingly, these shade‐induced responses, which are widely considered to be adaptive, did not differ between invasive and non‐invasive species. Main conclusions We conclude that high biomass production across different light environments pre‐adapts species to become invasive, and that this is not mediated by plasticities of the morphological traits that we measured.     

Melanoma progression exhibits a significant impact on connexin expression patterns in the epidermal tumor microenvironment

Melanoma depends on, interacts with and reacts to the stroma in which it is embedded, including fibroblasts, extracellular matrix, endothelial cells and immune cells. However, the impact of melanoma on the epidermal tumor microenvironment—the multilayered epithelium of the skin—is poorly understood. Gap junctions are essential for intercellular communication and involved in proliferation, differentiation and homeostasis of keratinocytes. We have shown previously that the gap junction proteins connexin 26 and 30 (Cx26 and Cx30) are induced in the epidermal tumor microenvironment of skin cancers including melanoma. This study compares the extent of Cx26, Cx30 and Cx43 expression in the epidermal microenvironment of melanocytic nevi and melanomas and its association with melanoma thickness, proliferative index of the tumor and its microenvironment, and with 5-year metastasis and survival. We found that induction of Cx26 and Cx30 cell–cell border expression in the epidermal tumor microenvironment correlates to malignancy. Importantly, there was a significant correlation of tumor thickness with the vertical epidermal Cx26 and Cx30 expression pattern and the horizontal Cx26 dissemination. Furthermore, horizontal Cx26 expression correlated with metastasis. Vertical epidermal expression patterns of Cx26 and Cx30 significantly correlated with the proliferative index in the epidermal tumor microenvironment but not with the proliferative index in the tumor. In contrast, Cx43 did not correlate with malignancy, thickness or proliferative index. In summary, here we show for the first time a significant association between the progression of melanoma and alterations in its epithelial tumor microenvironment.