Virchows Archiv Fur Pathologische Anatomie Und Physiologie Und Fur Klinische Medizin最新文献

Vasculogenesis is a complex process by which endothelial stem and progenitor cells undergo de novo vessel formation. Quantitative assessment of vasculogenesis is a central readout of endothelial progenitor cell functionality. However, current assays lack kinetic measurements. To address this issue, new approaches were developed to quantitatively assess in vitro endothelial colony-forming cell (ECFC) network formation in real time. Eight parameters of network structure were quantified using novel Kinetic Analysis of Vasculogenesis (KAV) software. KAV assessment of structure complexity identified two phases of network formation. This observation guided the development of additional vasculogenic readouts. A tissue cytometry approach was established to quantify the frequency and localization of dividing ECFCs. Additionally, Fiji TrackMate was used to quantify ECFC displacement and speed at the single-cell level during network formation. These novel approaches were then implemented to identify how intrauterine exposure to maternal diabetes mellitus (DM) impairs fetal ECFC vasculogenesis. Fetal ECFCs exposed to maternal DM form fewer initial network structures, which are not stable over time. Correlation analyses demonstrated that ECFC samples with greater division in branches form fewer closed network structures. Additionally, reductions in average ECFC movement over time decrease structural connectivity. Identification of these novel phenotypes utilizing the newly established methodologies provides evidence for the cellular mechanisms contributing to aberrant ECFC vasculogenesis.

Black band disease (BBD) is a widespread coral pathology caused by a microbial consortium dominated by cyanobacteria, which is significantly contributing to the loss of coral cover and diversity worldwide. Since the effects of the BBD pathogens on the physiology and cellular stress response of coral polyps appear almost unknown, the expression of some molecular biomarkers, such as Hsp70, Hsp60, HO-1, and MnSOD, was analyzed in the apparently healthy tissues of Goniopora columna located at different distances from the infection and during two disease development stages. All the biomarkers displayed different levels of expression between healthy and diseased colonies. In the healthy corals, low basal levels were found stable over time in different parts of the same colony. On the contrary, in the diseased colonies, a strong up-regulation of all the biomarkers was observed in all the tissues surrounding the infection, which suffered an oxidative stress probably generated by the alternation, at the progression front of the disease, of conditions of oxygen supersaturation and hypoxia/anoxia, and by the production of the cyanotoxin microcystin by the BBD cyanobacteria. Furthermore, in the infected colonies, the expression of all the biomarkers appeared significantly affected by the development stage of the disease. In conclusion, our approach may constitute a useful diagnostic tool, since the cellular stress response of corals is activated before the pathogens colonize the tissues, and expands the current knowledge of the mechanisms controlling the host responses to infection in corals.

Activation of telomerase is a critical step in the development of about 85 % of human cancers. Levels of Tert, which encodes the reverse transcriptase subunit of telomerase, are limiting in normal somatic cells. Tert is subjected to transcriptional, post-transcriptional and epigenetic regulation, but the precise mechanism of how telomerase is re-activated in cancer cells is poorly understood. Reactivation of the Tert promoter involves multiple changes which evolve during cancer progression including mutations and chromosomal re-arrangements. Newly described non-coding mutations in the Tert promoter region of many cancer cells (19 %) in two key positions, C250T and C228T, have added another layer of complexity to telomerase reactivation. These mutations create novel consensus sequences for transcription factors which can enhance Tert expression. In this review, we will discuss gene structure and function of Tert and provide insights into the mechanisms of Tert reactivation in cancers, highlighting the contribution of recently identified Tert promoter mutations.

The aim of the experiment on 100 cross-bred barrows was to compare commercial diets for fattening pigs based on either soya bean meal (SBM) imported from non-European countries with diets based on a mixture of locally produced rape seed meal, distillers' dried grains with solubles and soya beans as main protein sources. In addition, these both types of diets were processed by two different technical feed treatments, i.e. coarse grinding without hydrothermal treatment or fine grinding and pelleting. With only few exceptions, nutrients of the diet without SBM were more digestible (p < 0.05) resulting in a higher metabolisable energy (ME) content. Fine grinding and pelleting increased also the ME content and the nutrient digestibility with the exception of crude fibre. Higher feed intake of animals that fed diets without SBM (p < 0.01) resulted in higher average daily gain (p < 0.01). However feeding this diet, the higher digestibility was not reflected in a decreased feed-to-gain ratio (FGR), but fine grinding and pelleting reduced FGR (p < 0.001). A higher pH value and a lower DM content of caecal chymus were detected in animals that received coarsely ground feed (p < 0.05). Animals that fed finely ground and pelleted feed had higher slaughter and relative liver weights and higher blood cholesterol concentrations (p = 0.040). The urea concentrations of blood were lower (p = 0.019) after feeding diets without SBM. In conclusion, SBM imported from non-European countries can be replaced by alternative local protein sources without compromising digestibility or performances of animals. Although fine grinding and thermal treatment particularly seemed to be advantageous for digestibility and performance, the possible risk of development of stomach lesions should be considered.