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Progression through the cell cycle in eukaryotic cells is controlled by a family of protein kinases, termed cyclin-dependent kinases (CDKs), and their specific partners, the cyclins. In particular, the control of mammalian cell proliferation occurs largely during the G1 phase of the cell cycle. Five mammalian G1 cyclins have been enumerated to date: cyclins D1, D2, and D3 (D-type cyclins), and cyclins E and E2. By the use of immunohistochemistry and immunoelectron microscopy, we observed that in the first trimester of gestation of human placenta, cyclin D1 was distributed in the nuclei of the cytotrophoblast compartment together with a weak positivity of endothelial cells surrounding blood vessels. The endothelial positivity of cyclin D1 strongly increased in the third trimester of gestation. Moreover, we observed the subcellular localization of cyclin D1 that was present both in the stroma of placental villi and in the nuclei of syncytiotrophoblast cells. Therefore, we observed that CDK4 was localized in the nuclei of the cytotrophoblast compartment during the first and third trimesters and it also had a nuclear positivity in the endothelial cells of blood vessels at the end of the third trimester of gestation. In conclusion we may hypothesize that cyclin D1/CDK4 complex functions to regulate the cell cycle progression in the proliferative compartment of human placenta, the cytotrophoblast, during the first trimester through interaction with p107 and p130. Therefore, cyclin D1 and CDK4 seem to be involved in the control of placental angiogenesis during the third trimester of gestation.

The balance between cell death and cell proliferation and its regulation are essential features of many physiological processes and are particularly important in fetal morphogenesis and adult tissue homeostasis. Apoptosis is a type of cell suicide that is activated in two main ways: through a receptor-mediated pathway or through a mitochondrial pathway. We have investigated the immunohistochemical distribution of proteins belonging to these two pathways in human placenta during gestation by comparing their expression levels between the first and third trimester of gestation. In the first trimester, the receptor-mediated pathway prevails over the mitochondrial pathway with a moderate/intense expression of its three components, viz., Fas ligand (FasL), Fas, and caspase-8, and weak positivity of anti-apoptotic FLIP, these proteins being mainly localized in the cytotrophoblast compartment. In the third trimester of gestation, there is an increased expression of mitochondrial pathway proteins, viz., Apaf-1 and caspase-9. We have also investigated the expression level of caspase-3, the primary effector caspase of both pathways, and have observed that it is moderately expressed during gestation, being mainly localized in the cytotrophoblast during the first trimester and in both placental compartments during the third trimester of gestation. Thus, both pathways actively function in human placenta to execute cell death. By means of immunoelectron microscopy, we have further shown that, in human placenta, the two proteins of the mitochondrial pathway together with caspase-3 are localized both in the cytoplasm and in the nucleus. In particular, Apaf-1 and caspase-9 are distributed near to the nuclear envelope suggesting an important role for these two proteins in disrupting the nuclear-cytoplasmic barrier.

Apelin is a novel bioactive peptide that has been isolated from bovine stomach extracts and identified as the endogenous ligand for the APJ receptor. Although the main physiological functions of apelin have not yet been clarified, it is known that apelin is involved in the regulation of blood pressure, central control of body fluid homeostasis and the modulation of immune response. In order to investigate the distribution of apelin in reptiles, we have performed an immunohistochemical analysis on tissues of the lizard Podarcis sicula. The peptide was found to be widely distributed, although its cellular localization differed in the various organs examined. A strong immunopositivity was found in the heart, stomach and intestine. In the spleen, an intense apelin immunopositivity was restricted to a discrete number of cells scattered throughout the red pulp and co-localized with immunoglobulin kappa and lambda chains, suggesting an analogous function of this peptide in immune responses also in reptiles. Intriguingly, apelin immunoreactivity was discretely localized in endothelial cells in the lung and thyroid gland. In the light of these data, we conclude that apelin may have multiple functions in reptiles.

Background Emergence of dysplastic haematopoietic precursor/s, cytopenia and variable leukaemia risk characterise myelodysplastic syndromes (MDS). Impaired immune‐regulation, preferentially affecting cytotoxic T cells (CTL), has been largely observed in MDS. Recently, we described the TR3−56 T cell subset, characterised by the co‐expression of CD3 and CD56, as a novel immune‐regulatory population, able to modulate cytotoxic functions. Here, we address the involvement of TR3−56 cells in MDS pathogenesis/progression. Objectives To analyse the relationship between TR3−56 and CTL activation/expansion in bone marrow (BM) of very‐low/low‐risk MDS subjects. Methods Peripheral blood and BM specimens, obtained at disease onset in a cohort of 58 subjects, were analysed by immune‐fluorescence and flow cytometry, to preserve the complexity of the biological sample. Results We observed that a trend‐increase of BM TR3−56 in high/very‐high MDS stage, as compared with very‐low/low group, associates with a decreased activation of BM resident CTL; significant correlation of TR3−56 with BM blasts has been also revealed. In addition, in very‐low/low‐risk subjects the TR3−56 amount in BM inversely correlates with the presence of activated BM CTL showing a skewed Vβ T‐cell repertoire. Conclusions These data add TR3−56 to the immune‐regulatory network involved in MDS pathogenesis/progression. Better knowledge of the immune‐mediated processes associated with the disease might improve MDS clinical management.

Tourism is an important economic sector in many countries. Touristic mobility depends on the availability of touristic assets in different locations, as well as on the access to different activities (bathing, leisure, culture, etc.) at different places. The consumption of different activities, the frequency at which these are accessed, the (active) accessibility to activities of candidate locations for staying, the level and distribution in the region of touristic assets, all of these are variables of an analytical model able to represent in an aggregate way how the opportunities for staying are distributed across the candidate temporary accommodation in the region. The model is based on the random utility theory, in particular on the concept of inclusive value, used in order to compute appropriate accessibility indexes. The proposed model can be exploited by two different points of view. The main is the point of view of the suppliers of touristic services; these could allow the tourist to access a web-based platform to be queried for an aggregate map of the touristic accessibilities of different zones in a pre- selected large touristic region. The map can be different for different tourists with different needs, changing on the base of the desired activities as ranked in input by the tourist during the querying procedure. Another point of view is the one of the public authority responsible for the promotion of touristic activities and the support/planning of touristic facilities. The application of the model and the exploitation of the accessibility concept is presented in the paper with reference to a case of study, the Campania region in the south of Italy, characterised by a large variety of touristic assets and opportunities ranging from cultural heritage to bathing localities, from wine and food to naturalistic assets, et cetera

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