ROCK ‘n TOR: An Outlook on Keratinocyte Stem Cell Expansion in Regenerative Medicine via Protein Kinase Inhibition

Keratinocyte stem cells play a fundamental role in homeostasis and repair of stratified epithelial tissues. Transplantation of cultured keratinocytes autografts provides a landmark example of successful cellular therapies by restoring durable integrity in stratified epithelia lost to devastating tissue conditions. Despite the overall success of such procedures, failures still occur in case of paucity of cultured stem cells in therapeutic grafts. Strategies aiming at a further amplification of stem cells during keratinocyte ex vivo expansion may thus extend the applicability of these treatments to subjects in which endogenous stem cells pools are depauperated by aging, trauma, or disease. Pharmacological targeting of stem cell signaling pathways is recently emerging as a powerful strategy for improving stem cell maintenance and/or amplification. Recent experimental data indicate that pharmacological inhibition of two prominent keratinocyte signaling pathways governed by apical mTOR and ROCK protein kinases favor stem cell maintenance and/or amplification ex vivo and may improve the effectiveness of stem cell-based therapeutic procedures. In this review, we highlight the pathophysiological roles of mTOR and ROCK in keratinocyte biology and evaluate existing pre-clinical data on the effects of their inhibition in epithelial stem cell expansion for transplantation purposes

Mechanisms for longitudinal transport on early life stages in benthic-pelagic fishes within a tide-dominated estuary

Mechanisms that control the longitudinal transport of larvae and juveniles in nursery grounds such as estuaries are reported for some species. However, the behaviour and population consequences of these mechanisms are still uncertain. In this study, we tested selective tidal-stream transport from the along-channel (up-and down-stream) and cross-channel (from one margin to the other) perspectives for two kinds of fish: estuarine-resident gobies (Pomatoschistus spp.) and marine estuarine-opportunistic anchovies (Engraulis encrasicolus). Three cruises were conducted in the lower Guadalquivir estuary, on the ebb and on the flood of spring tides in summer. Plankton samples were collected across a channel section, at three stations (one in the middle of the channel and two in adjacent shallower areas), near the surface and near the bottom simultaneously. In addition, multiple physico-chemical variables (temperature, turbidity, dissolved oxygen, pH, salinity, chlorophyll-a, along with wind and current direction and velocity) were measured to examine the different correlations used by the studied fish in their strategies. The benthic distribution of gobies indicated that they used flood currents near the bottom of lateral (shallow) areas to ingress into and remain in the estuary, temperature and/or dissolved oxygen being their main possible cues. On the contrary, the anchovies were more abundant near the surface, especially on the ebb tide, showing downstream advection, which was mainly influenced by salinity. However, the largest indi-vidual anchovies in the lateral/shallow zones suggested a behavioural ontogeny, which, together with wind induced transport, could contribute to their retention. This comparison also enhanced the knowledge of the habitat distribution of two species common and abundant in estuaries, anchovies and gobies.info:eu-repo/semantics/publishedVersio

Molecular Basis of Phenylketonuria in Italy

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Management of risk of breast carcinoma in postmenopausal women.

Breast carcinoma is the most frequent tumor in the female population. Many factors can influence the risk of breast cancer; some of them, such as old age and breast cancer 1/2 (BRCA1/BRCA2) gene mutations, are associated with a fourfold increase in risk. A previous diagnosis of atypical ductal or lobular hyperplasia or having a first-degree relative with a carcinoma are factors associated with a two- to fourfold increase in risk. A relative risk between 1 and 2 is associated with longer exposure to endogenous hormones as a result of early menarche, late menopause and obesity, or with recent and prolonged use of hormone replacement therapy (HRT) or with behavioural factors such as high alcohol and fat intake. Is it possible to modify breast cancer risk in postmenopausal women? Risk factors related to lifestyle can be changed, even if it is not clear whether modifying these behavioural factors during the postmenopausal period will influence the overall breast cancer risk. For instance, the influence of exogenous hormones throughout life (both oral contraceptives and HRT) should be evaluated according to the individual risk-benefit ratio. The problem is even more complex for women who carry genetic mutations and for those who have close relatives with breast cancer, who may be candidates for risk reduction strategies. Prophylactic bilateral mastectomy is still controversial, but is frequently offered to or requested by this group of women and may be indicated in BRCA1/BRCA2 carriers. Chemoprevention with tamoxifen and with the new selective estrogen receptor modulators, namely raloxifene, is very promising and deserves a thorough discussion for all high-risk women

The "O3E" program: raising awareness on natural hazards

Earthquakes may be traumatic events and as many other environmental emergencies, like storm or floods, may cause more damages than expected when who experiences the phenomena does not know how to behave in the fall. Provided that it is always not feasible to rely on prediction when dealing with earthquakes or extreme meteorological events, preparedness proves to be an efficient (and certainly the most recommendable and cheap) way to face emergencies. Education and training are thus two ingredients to help citizens to perceive the scientific information formerly confined in the laboratories, in particular in the domain of the environmental risk. The “O3E” innovative program (European Observatory for Education and Environment) is established after 10 years (1997-2007) of regional and national original programs (“Sismos of the Schools”), and from Italian and Swiss experiences concerning environment tools for education. The project, that is a cooperation between France, Italy and Switzerland, is born to promote a responsible behaviour of citizens in front of the evolution of a society where scientific information is promptly available. ARGAL (Agency for Geological Risk in the Latin Arc) operates the administrative and technical coordination. The objective of this program is to create a school network in the Alpine and Mediterranean areas equipped with environmental sensors of an educational vocation. The data on the movement of the ground (seismometers), the temperatures and precipitations (weather stations), the flows of rivers (hydrogeology) recorded in the schools and processed by the students are collected on dedicated servers and then made available through internet to the entire educational community. This network “O3E”, once installed, is the starting point of activities. Indeed, various general objectives are pursued: - To promote the applied sciences and new technologies. - To put in network the actors of Education and formation. - To develop the sense of the autonomy and the responsibility in the young people. - To reinforce and develop relationships with regional partners of the educational and university fields. - To support a rational awakening for the prevention of the natural risks that can make the difference during the event in terms of safety. With these premises, the “O3E” experience sets up a permanent educational network of citizens in the Alpine and Mediterranean areas, building an exchange of knowledge on natural risks prevention.PublishedAix en Provence5.9. Formazione e informazioneope