The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that encodes the FUS-CHOP chimeric protein, is associated with human liposarcomas. The altered expression of FUS-CHOP has been implicated in a characteristic subgroup of human liposarcomas. We have introduced the FUS-CHOP transgene into the mouse genome in which the expression of the transgene is successfully driven by the elongation factor 1a (EF1a) promoter to all tissues. The consequent overexpression of FUS-CHOP results in most of the symptoms of human liposarcomas, including the presence of lipoblasts with round nuclei, accumulation of intracellular lipid, induction of adipocyte-speci®c genes and a concordant block in the di erentiation program. We have demonstrated that liposarcomas in the FUS-CHOP transgenic mice express high levels of the adipocyte regulatory protein PPARg, whereas it is not expressed in embryonic ®broblasts from these animals following induction to di erentiation toward the adipocyte lineage, indicating that the in vitro system does not really re¯ect the in vivo situation and the developmental defect is downstream of PPARg expression. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1a promoter. This establishes FUS-CHOP overexpression as a key determinant of human liposarcomas and provide the ®rst in vivo evidence for a link between a fusion gene created by a chromosomal translocation and a solid tumor.

We derive source integrals for multipole moments that describe the behavior of static and axially symmetric spacetimes close to spatial infinity. We assume that the matter distribution is isolated. We outline also some applications of these source integrals of the asymptotic multipole moments.

The Poincaré group can be interpreted as the group of isometries of a Minkowskian space. This point of view suggests to consider the group of isometries of a given space as the suitable group to construct a gauge theory of gravity. We extend these ideas to the case of maximally symmetric spaces to reach a realistic theory including the presence of a cosmological constant. Introducing the concept of "minimal tetrads" we deduce Einstein gravity in the vacuum as a gauge theory of translations.

Catalytic cancer therapy is emerging as a powerful tool to target cancer cells by exploiting specific characteristics of the tumor microenvironment (TME). To this end, the catalytic activity of nanoparticles, enzymes and homogeneous catalysts is recruited to induce reactions that are damaging to cancer cells. Thus, the pro-drug activation approach uses chemical constructs that become toxic species inside the tumor, typically following removal of a protecting group. In contrast, TME-based catalytic strategies do not rely on the introduction of foreign species and instead use molecules that are already present in the TME. So far, only four processes have been explored in relation to cancer therapy, two oxidation reactions (glucose and glutathione), generation of reactive oxygen species (ROS) and production of oxygen to alleviate tumor hypoxia. This is surprising, since the rich chemical environment in tumor cells could in principle provide many other therapeutic opportunities. In particular, amino groups seem a suitable target, given the abundance of proteins and peptides in biological environments. Here we show that catalytic CuFe nanoparticles are able to foster transamination reactions between different amino acids and pyruvate, another key molecule that abounds in the TME. Transamination would then reduce the available aminoacid pool, which is likely to affect cell homeostasis and to effectively hinder tumor proliferation. After internalization of Cu-containing nanoparticles in U251-MG cells, we observed a significant decrease in glutamine and alanine levels up to 48 hours after treatment. In addition, we have found that not only simple amino acids, but also di- and tri-peptides undergo catalytic transamination when exposed to the Cu cations released by our nanoparticles, thus extending the range of the effects to other molecules such as GSSG. Mechanistic calculations for GSSG transamination revealed the formation of an imine between the oxo-group of pyruvate and the free -NH2 group of GSSG, followed by the coordination of the imine to Cu(II). Our results demonstrate that transamination reactions can be catalyzed in cellulo by Cu-releasing nanoparticles, adding a new reaction to the existing toolbox of catalytic therapies.