Opening the Gate to the Serism Project: From Earth to Space and Back

In the context of Space Medicine, the aim of “SERiSM” (Role of the Endocannabinoid System in Reprogramming human pluripotent Stem cells under Microgravity) project, selected by the Italian Space Agency, was to study the involvement of the endocannabinoid system (ECS) in the osteogenic differentiation under real microgravity. An innovative and easily accessible stem cell model derived from human blood (human blood-derived stem cells, hBDSCs) was used to this purpose. This model is autologous and possesses a remarkable proliferative and differentiative capacity underground gravity conditions, with high therapeutic potential for bone degenerative diseases. ECS is a fine network of proteins that interact to regulate the endogenous levels of lipid mediators, collectively termed endocannabinoids (eCBs), which in turn are involved in cell communication and in the mechanisms governing the switch between cell life and death. In the frame of the VITA mission, led by European Space Agency (ESA) astronaut Paolo Nespoli, we analyzed the differentiation process also under microgravity condition and evaluated the expression of ECS proteins through immunoassay methods. Our results demonstrate that some elements of the ECS are modulated during the differentiation process and in microgravity, supporting the idea that increased levels of anandamide are indeed need to stimulate type-1 cannabinoid receptor. In conclusion, microgravity could drive endocannabinoid signalling in the former stages of hBDSCs differentiation

Human Endogenous Retrovirus K in the Crosstalk Between Cancer Cells Microenvironment and Plasticity: A New Perspective for Combination Therapy

Abnormal activation of human endogenous retroviruses (HERVs) has been associated with several diseases such as cancer, autoimmunity, and neurological disorders. In particular, in cancer HERV activity and expression have been specifically associated with tumor aggressiveness and patient outcomes. Cancer cell aggressiveness is intimately linked to the acquisition of peculiar plasticity and heterogeneity based on cell stemness features, as well as on the crosstalk between cancer cells and the microenvironment. The latter is a driving factor in the acquisition of aggressive phenotypes, associated with metastasis and resistance to conventional cancer therapies. Remarkably, in different cell types and stages of development, HERV expression is mainly regulated by epigenetic mechanisms and is subjected to a very precise temporal and spatial regulation according to the surrounding microenvironment. Focusing on our research experience with HERV-K involvement in the aggressiveness and plasticity of melanoma cells, this perspective aims to highlight the role of HERV-K in the crosstalk between cancer cells and the tumor microenvironment. The implications for a combination therapy targeted at HERVs with standard approaches are discussed

Metodo di espansione di cellule staminali adulte da sangue periferico e relativi usi in campo medico

A method for the expansion of adult stem cells from blood, particularly but not only peripheral blood, involves removing adult stem cells from blood of a mammal, immediately expanding the stem cells via in-vitro treatment with MCSF (Macrophage Colony Stimulating Factor) at a concentration of about 8-15 nM, and purifying the expanded stem cells. Compositions and methods of using the expanded adult stem cells are also described

Kit for collecting blood, preferably peripheral blood, for the production of stem cells

A kit for collecting blood, preferably peripheral blood, for the production of pluripotent stem cells comprises at least a first container, able to contain the blood taken, which contains an anticoagulant and the substance MCSF (Macrophage Colony Stimulating Factor). Read more: http://www.faqs.org/patents/app/20110017733#ixzz1WVD2PLW

Mutational destabilization of the critical interface water cluster in Scapharca dimeric hemoglobin: structural basis for altered allosteric activity

A cluster of interface ordered water molecules has been proposed to act as a key mediator of intersubunit communication in the homodimeric hemoglobin of Scapharca inaequivalvis. Mutations of Thr72 to Val and Ile, which lack the hydroxyl group to hydrogen bond the deoxy interface water molecules, result in sharply altered functional properties. We have determined the high resolution (1.6-1. 8 A) crystal structures of these two mutants in both the deoxygenated and CO-liganded states. These structures show minimal protein structural changes relative to the same native derivatives, despite greater than 40-fold increases in oxygen affinity. In the deoxy state of both mutants two water molecules at the periphery of the water cluster are lost, and the remaining cluster water molecules are destabilized. The CO-liganded structures show key differences between the two mutants including a more optimal interface packing involving Ile72 that acts to stabilize its high affinity (R) state. This additional stabilization allows rationalization of its lowered cooperativity within the context of a two-state model. These studies support a key role of ordered water in cooperative functioning and illustrate how subtle structural alterations can result in significantly altered functional properties in an allosteric molecule

Bovine tryptases. cDNA cloning, tissue specific expression and characterization of the lung isoform

A complementary DNA encoding a new bovine tryptase isoform (here named BLT) was cloned and sequenced from lung tissue. Analysis of sequence indicates the presence of a 26-amino acid prepro-sequence and a 245 amino acid catalytic domain. It contains six different residues when compared with the previously characterized tryptase from bovine liver capsule (BLCT), with the most significant difference residing at the primary specificity S1 pocket. In BLT, the canonical residues Asp-Ser are present at positions 188-189, while in BLCT these positions are occupied by residues Asn-Phe. This finding was confirmed by mass fingerprinting of the peptide mixture obtained upon in-gel tryptic digestion of BLT. Analysis by gel filtration of the purified protein shows that BLT is probably tetrameric, similar to the previously identified tryptases from other species, with monomer migrating as 35-40 kDa multiple bands in SDS/PAGE. As expected, the catalytic abilities of the two bovine tryptases are different. The specificity constant values (kcat/Km) assayed with model substrates are 10- to 60-fold higher in the case of BLT. The tissue-specific expression of the two tryptases was evaluated at the RNA level by analysis of their different restriction patterns. In lung, only BLT was found to be expressed, while in liver capsule only BLCT is present. Both isoforms are distributed in similar amounts in heart and spleen. Analysis of the two gene sequences reveals the presence of several recognition sequences in the promoter regions and suggest a role for hormones in governing the mechanism of tissue expression of bovine tryptases

TAp73 regulates ATP7A: possible implications for ageing-related diseases.

The p53 family member p73 controls a wide range of cellular function. Deletion of p73 in mice results in increased tumorigenesis, infertility, neurological defects and altered immune system. Despite the extensive effort directed to define the molecular underlying mechanism of p73 function a clear definition of its transcriptional signature and the extent of overlap with the other p53 family members is still missing. Here we describe a novel TAp73 target, ATP7A a member of a large family of P-type ATPases implicated in human neurogenerative conditions and cancer chemoresistance. Modulation of TAp73 expression influences basal expression level of ATP7A in different cellular models and chromatin immunoprecipitation confirmed a physical direct binding of TAp73 on ATP7A genomic regions. Bioinformatic analysis of expression profile datasets of human lung cancer patients suggests a possible implication of TAp73/ATP7A axis in human cancer. These data provide a novel TAp73-dependent target which might have implications in ageing-related diseases such as cancer and neurodegeneration.Department of Clinical & Experimental Medicine, University of Foggia, Italy 3 Department of Systems Medicine, Nephrology and Hypertension Unit, Tor Vergata University Hospital, Rome, Italy. 4 Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Ital

Analisi e previsioni dei prezzi delle commodity

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Analisi e previsioni dei prezzi delle commodity

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Analisi e previsioni dei prezzi delle commodity

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal