Endothelial-Mesenchymal Transition of Brain Endothelial Cells: Possible Role during Metastatic Extravasation

Cancer progression towards metastasis follows a defined sequence of events described as the metastatic cascade. For extravasation and transendothelial migration metastatic cells interact first with endothelial cells. Yet the role of endothelial cells during the process of metastasis formation and extravasation is still unclear, and the interaction between metastatic and endothelial cells during transendothelial migration is poorly understood. Since tumor cells are well known to express TGF-β, and the compact endothelial layer undergoes a series of changes during metastatic extravasation (cell contact disruption, cytoskeletal reorganization, enhanced contractility), we hypothesized that an EndMT may be necessary for metastatic extravasation. We demonstrate that primary cultured rat brain endothelial cells (BEC) undergo EndMT upon TGF-β1 treatment, characterized by the loss of tight and adherens junction proteins, expression of fibronectin, β1-integrin, calponin and α-smooth muscle actin (SMA). B16/F10 cell line conditioned and activated medium (ACM) had similar effects: claudin-5 down-regulation, fibronectin and SMA expression. Inhibition of TGF-β signaling during B16/F10 ACM stimulation using SB-431542 maintained claudin-5 levels and mitigated fibronectin and SMA expression. B16/F10 ACM stimulation of BECs led to phosphorylation of Smad2 and Smad3. SB-431542 prevented SMA up-regulation upon stimulation of BECs with A2058, MCF-7 and MDA-MB231 ACM as well. Moreover, B16/F10 ACM caused a reduction in transendothelial electrical resistance, enhanced the number of melanoma cells adhering to and transmigrating through the endothelial layer, in a TGF-β-dependent manner. These effects were not confined to BECs: HUVECs showed TGF-β-dependent SMA expression when stimulated with breast cancer cell line ACM. Our results indicate that an EndMT may be necessary for metastatic transendothelial migration, and this transition may be one of the potential mechanisms occurring during the complex phenomenon known as metastatic extravasation.     

Finite element analysis of different loading conditions for implant-supported overdentures supported by conventional or mini implants

The effect of implants’ number on overdenture stability and stress distribution in edentulous mandible, implants and overdenture was numerically investigated for implant-supported overdentures. Three models were constructed. Overdentures were connected to implants by means of ball head abutments and rubber ring. In model 1, the overdenture was retained by two conventional implants; in model 2, by four conventional implants; and in model 3, by five mini implants. The overdenture was subjected to a symmetrical load at an angle of 20 degrees to the overdenture at the canine regions and vertically at the first molars. Four different loading conditions with two total forces (120, 300 N) were considered for the numerical analysis. The overdenture displacement was about 2.2 times higher when five mini implants were used rather than four conventional implants. The lowest stress in bone bed was observed with four conventional implants. Stresses in bone were reduced by 61% in model 2 and by 6% in model 3 in comparison to model 1. The highest stress was observed with five mini implants. Stresses in implants were reduced by 76% in model 2 and 89% increased in model 3 compared to model 1. The highest implant displacement was observed with five mini implants. Implant displacements were reduced by 29% in model 2, and increased by 273% in model 3 compared to model 1. Conventional implants proved better stability for overdenture than mini implants. Regardless the type and number of implants, the stress within the bone and implants are below the critical limits.     

Rare species habitat suitability assessment and reliability evaluation of an expert-based model: A case study of the insectivorous plant Pinguicula crystallina Sibth. et Smith subsp. hirtiflora (Ten.) Strid (Lentibulariaceae)

The development of habitat suitability models requires a large amount of data which are rarely available. In this case, researchers need to get information on the ecological features of the studied species, based on the opinion of experts or on the literature, to construct a qualitative model. However, such models cannot be rigorously evaluated, as in most cases absence points are not available. In this paper, we assess the habitat suitability for a vulnerable insectivorous plant, Pinguicula crystallina Sibth. et Smith subsp. hirtiflora (Ten.) Strid (Lentibulariaceae) in the Campania region. Our aim was to develop an expert-based, presence-only model in support of possible conservation actions. Topographic and geological features of this species suggested by the literature were used in our model. Both the Boyce index and field surveys were chosen to evaluate the model's reliability. During field surveys, 31 absence sites and 1 new presence site were identified, and differences between sites with regard to water chemistry and quality were investigated, water being an element in the species habitat. Factors that affect reliability of the model, such as the lack of a large amount of information on the species and the limited spatial resolution of geographical information system data, are discussed.     

Impaired affinity for phenylalanine in Escherichia coli phenylalanyl-tRNA synthetase mutant caused by Gly-to-Asp exchange in motif 2 of class II tRNA synthetases

Phenylalanyl-tRNA synthetase (PheRS; alpha 2 beta 2 subunit structure) is a member of class II of tRNA synthetases. We report here the genetic analysis of an Escherichia coli mutant strain which is auxotrophic for phenylalanine because it has a PheRS with a decreased affinity for phenylalanine. The mutant pheS gene encoding the PheRS alpha subunit was cloned and sequenced, and the deviation from the wild-type gene was found to result in a Gly191-to-Asp191 exchange. This alteration is located within motif 2, one of 3 conserved sequence motifs characteristic for class II aminoacyl-tRNA synthetases. Motif 2 may thus participate in the formation of the phenylalanine binding site in PheRS.     

Results of studies on the effect of radiologic contamination after the Czernobyl catastrophe and prophylactic iodine on thyroid morphology and function of inhabitants of North-East Poland]

The results of the investigations of radioactive contamination after the Chernobyl catastrophe and subsequent iodine prophylaxis on the thyroid gland function and morphology in Northeast Poland. The aim of the study was to determine whether kalium iodine in one dose during radioactive contamination in Poland limited the radioactive dose in the thyroid gland and if significant disadvantageous side-effects in the intrathyroid and extrathyroid occurred. Additionally during the studies we tried to determine if radioactive iodine contamination which occurred in the region of the Medical Academy in Bia?ystok caused an increase in thyroid disease. It is interesting to note the different results obtained after radioactive contamination with the results from the investigations in this same territory in 1983-1985. In 1983-1985, before the Chernobyl catastrophe, 6,921 persons in Northeast Poland were investigated. In 1986-1988, immediately after the disaster 4,010 persons were investigated. The main study according to grant No MZ-XVII was carried out in three provinces: Bia?ystok, Suwa?ki and Olsztyn. In this investigation 10,011 persons born before April 26, 1986 and after January 1, 1936 participated, 5,789 townspeople and 4,222 villagers, 3,987 children up to 16 years of age it the time of the disaster 1,973 boys and 2,009 girls; 6,024 adults 2,509 men and 3,516 women were drawn from a register. Committed doses to the thyroid in the investigated region were one of the highest in Poland and depended on age group and were depended on time of prophylaxis non proportional. Iodine prophylaxis was provided mainly with one dose of Lugol solution about 90%, 95% children and 30% adults took iodine. The majority of the population (53.3%-74%) were given iodine in April. From May 1st to 5th 23.0-43.4% received iodine, but after May 5th very few persons. Iodine was well tolerated, but Lugol Solution was better tolerated than other kinds of iodine. Only 241 (4.4%) cases had side effects, mainly vomiting (143), symptoms such as stomach ache, diarrhea, dyspnoe, skinrash etc. in lesser numbers. 12% (29 persons) were seen by a physician. In the investigated population were 200 pregnant women aged 19-40 years of which the majority (177) delivered full term healthy babies. Only 1 interrupted pregnancy and 7 had spontaneous abortion. Changes in the thyroid were noticed by 187 persons (2.3%-11.7%) most of which were enlargement of the thyroid, but only a few were confirmed by a physician. In the studied population from 1989 to 1990 over 30% of the population had struma.(ABSTRACT TRUNCATED AT 400 WORDS)