Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated,Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases

Bone metastases from prostate cancer (PCa) result from a complex cross-talk between PCa cells and osteoblasts (OB). Thus, targeting this interplay has become an attractive strategy to interfere with PCa bone dissemination. The agents currently used in clinical trials have proved ineffective, boosting research to identify additional mechanisms that may be involved in this two-directional talk. Here, we investigated whether and how 5-hydro-5-methylimidazolone (MG-H1), a specific methylglyoxal (MG)-derived advanced glycation end product (AGE), was a novel player in the dialogue between PCa and OB to drive PCa bone metastases. Conditioned medium from osteotropic PC3 PCa cells, pre-treated or not with a specific MG scavenger, was administrated to human primary OB and cell morphology, mesenchymal trans-differentiation, pro-osteogenic determinants, PCa-specific molecules, and migration/invasion were studied by phase-contrast microscopy, real-time PCR, western blot and specific assays, respectively. We found that PC3 cells were able to release MG-H1 that, by binding to the receptor for AGEs (RAGE) on OB, reprogrammed them into a less-differentiate phenotype, endowed with some PCa-specific molecular features and malignant properties, in a mechanism involving reactive oxidative species (ROS) production and NF-kB pathway activation. These findings provide novel insights into the mechanisms of PCa osteoblastic metastases and foster in vivo research toward new therapeutic strategies interfering with PCa/OB cross-talk.     

The Involvement of Long Non-Coding RNAs in Bone

A harmonious balance between osteoblast and osteoclast activity guarantees optimal bone formation and resorption, pathological conditions affecting the bone may arise. In recent years, emerging evidence has shown that epigenetic mechanisms play an important role during osteoblastogenesis and osteoclastogenesis processes, including long non-coding RNAs (lncRNAs). These molecules are a class of ncRNAs with lengths exceeding 200 nucleotides not translated into protein, that have attracted the attention of the scientific community as potential biomarkers to use for the future development of novel diagnostic and therapeutic approaches for several pathologies, including bone diseases. This review aims to provide an overview of the lncRNAs and their possible molecular mechanisms in the osteoblastogenesis and osteoclastogenesis processes. The deregulation of their expression profiles in common diseases associated with an altered bone turnover is also described. In perspective, lncRNAs could be considered potential innovative molecular biomarkers to help with earlier diagnosis of bone metabolism-related disorders and for the development of new therapeutic strategies.     

The application of cryo-SEM techniques to the study of the symbiotic association in the Azolla leaf cavity

The preparation of frozen-hydrated samples for scanning electron microscopy to observe symbionts in Azolla is described and compared to the conventional method of chemical fixation followed by critical-point drying. The frozen-hydrated specimens preserve the structure of the associating symbionts and the liquid phase in the Azollaleaf cavity. The leaf cavity structure and the endosymbionts in the frozen-hydrated specimens were intact and unharmed throughout the fixation. The cyanobiont cells were distributed along the envelope of the leaf cavity, and did not aggregate around the hair cells, as reported for chemical fixation specimens. The mucilage layer removed by the chemical fixation could be observed in the cryo-fixation specimens, especially at the lower part of the cavity.     

Computation of nodes and weights of extended Gaussian rules

The numerical construction of the Kronrod extension to then-points Gauss-Gegenbauer integration rule and some extensions of Radau and Lobatto type are considered. A program for their purpose is described and some numerical examples are reported.     

Epigenetics and the germline

Epigenetic processes affect three stages of germline development, namely (1) specification and formation of primordial germ cells and their germline derivatives through lineage-specific epigenetic modifications, in the same manner as other embryonic lineages are formed, (2) a largely genome-wide erasure and re-establishment of germline-specific epigenetic modifications that only occurs in the embryonic primordial germ cell lineage, followed by re-establishment of sex-specific patterns during gametogenesis, and (3) differential epigenetic modifications to the mature male and female gamete genomes shortly after fertilisation. This review will detail current knowledge of these three processes both at the genome-wide level and at specific imprinted loci. The consequences of epigenetic perturbation are discussed and new in vitro models which may allow further understanding of a difficult developmental period to study, especially in the human, are highlighted.     

A WebGIS for the dissemination of information on historical landslides and floods in Umbria, Italy

A web site was designed to disseminate new information on historical landslides and floods in Umbria, central Italy. The historical information was compiled through a thorough review of existing catalogues of historical landslide and flood events, supplemented by an extensive search of local historical archives and chronicles, for the period before 1900. The new catalogue lists 1983 landslide events in the period from 1139 to 2001, and 1956 flood events in the period from 860 to 2001. In the considered period, in Umbria there were at least 1,531 sites affected one or more times by landslides, and at least 1,071 sites affected one or more times by inundations. The seasonal distribution of landslides and inundations was found different before and after 1900, most probably because of incompleteness of the historical record prior to 1900. WebGIS technology was used to disseminate the geographical and thematic information on historical landslides and floods in Umbria. The GIS-based web site is aimed at a diversified audience of experts and private citizens seeking information on geo-hydrological hazards in Umbria.

Personal Digital Assistant in an orthopaedic wireless ward: the HandHealth project

Personal Digital Assistant devices are becoming a frequently used device for the bedside care of the patient. Ways of application are many, but limitations are also numerous. Input device and monitor resolution are limited by the device size. Moreover, the choice of specific programs and the amount of storable data are limited by the quantity of memory. During HandHealth project a system was developed using a different point of view. Personal Digital Assistant is only a means to access data and use functionalities that are stored in a remote server. Using that system patient ward note can be showed and collected on the handheld device but saved directly on the Hospital Information System. Medical images can be showed on the device display, but also transferred to a high-resolution monitor. Large amount of data can be dictated and translated by remote continuous speech recognition.