New Strategies to Prolong the In Vivo Life Span of Iron-Based Contrast Agents for MRI

Superparamagnetic iron oxide (SPIO) and ultra small superparamagnetic iron oxide (USPIO) nanoparticles have been developed as magnetic resonance imaging (MRI) contrast agents. Iron oxide nanoparticles, that become superparamagnetic if the core particle diameter is ^~ 30nm or less, present R1 and R2 relaxivities which are much higher than those of conventional paramagnetic gadolinium chelates. Generally, these magnetic particles are coated with biocompatible polymers that prevent the agglomeration of the colloidal suspension and improve their blood distribution profile. In spite of their potential as MRI blood contrast agents, the biomedical application of iron oxide nanoparticles is still limited because of their intravascular half-life of only few hours; such nanoparticles are rapidly cleared from the bloodstream by macrophages of the reticulo-endothelial system (RES). To increase the life span of these MRI contrast agents in the bloodstream we proposed the encapsulation of SPIO nanoparticles in red blood cells (RBCs) through the transient opening of cell membrane pores. We have recently reported results obtained by applying our loading procedure to several SPIO nanoparticles with different chemical physical characteristics such as size and coating agent. In the current investigation we showed that the life span of iron-based contrast agents in the mice bloodstream was prolonged to 12 days after the intravenous injection of murine SPIO-loaded RBCs. Furthermore, we developed an animal model that implicates the pretreatment of animals with clodronate to induce a transient suppression of tissue macrophages, followed by the injection of human SPIO-loaded RBCs which make it possible to encapsulate nanoparticle concentrations (5.3-16.7mM Fe) higher than murine SPIO-loaded RBCs (1.4-3.55mM Fe). The data showed that, when human RBCs are used as more capable SPIO nanoparticle containers combined with a depletion of tissue macrophages, Fe concentration in animal blood is 2-3 times higher than iron concentration obtained by the use of murine SPIO-loaded RBCs.     

Sexual signalling in Propithecus verreauxi: male "chest badge" and female mate choice

Communication, an essential prerequisite for sociality, involves the transmission of signals. A signal can be defined as any action or trait produced by one animal, the sender, that produces a change in the behaviour of another animal, the receiver. Secondary sexual signals are often used for mate choice because they may inform on a potential partner's quality. Verreaux's sifaka (Propithecus verreauxi) is characterized by the presence of two different morphs of males (bimorphism), which can show either a stained or clean chest. The chest becomes stained by secretions of the sternal gland during throat marking (rubbing throat and chest on a vertical substrate while smearing the scent deposition). The role of the chest staining in guiding female mate choice was previously hypothesized but never demonstrated probably due to the difficulty of observing sifaka copulations in the wild. Here we report that stained-chested males had a higher throat marking activity than clean-chested males during the mating season, but not during the birth season. We found that females copulated more frequently with stained-chested males than the clean-chested males. Finally, in agreement with the biological market theory, we found that clean-chested males, with a lower scent-releasing potential, offered more grooming to females. This "grooming for sex" tactic was not completely unsuccessful; in fact, half of the clean-chested males copulated with females, even though at low frequency. In conclusion, the chest stain, possibly correlated with different cues targeted by females, could be one of the parameters which help females in selecting mates.     

The role of terrestriality in promoting primate technology

"Complex technology" has often been considered a hallmark of human evolution. However, recent findings show that wild monkeys are also capable of habitual tool use. Here we suggest that terrestriality may have been of crucial importance for the innovation, acquisition, and maintenance of "complex" technological skills in primates. Here we define complex technological skills as tool-use variants that include at least two tool elements (for example, hammer and anvil), flexibility in manufacture or use (that is, tool properties are adjusted to the task at hand), and that skills are acquired in part by social learning. Four lines of evidence provide support for the terrestriality effect. First, the only monkey populations exhibiting habitual tool use seem to be particularly terrestrial. Second, semi-terrestrial chimpanzees have more complex tool variants in their repertoire than does their arboreal Asian relative, the orangutan. Third, tool variants of chimpanzees used in a terrestrial setting tend to be more complex than those used exclusively in arboreal contexts. Fourth, the higher frequency in tool use among captive versus wild primates of the same species may be attributed in part to a terrestriality effect. We conclude that whereas extractive foraging, intelligence, and social tolerance are necessary for the emergence of habitual tool use, terrestriality seems to be crucial for acquiring and maintaining complex tool variants, particularly expressions of cumulative technology, within a population. Hence, comparative evidence among primates supports the hypothesis that the terrestriality premium may have been a major pacemaker of hominin technological evolution.     

Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy

Exosomes are endosome-derived nanovesicles actively released into the extracellular environment and biological fluids, both under physiological and pathological conditions, by different cell types. We characterized exosomes constitutively secreted by HER2-overexpressing breast carcinoma cell lines and analyzed in vitro and in vivo their potential role in interfering with the therapeutic activity of the humanized antibody Trastuzumab and the dual tyrosine kinase inhibitor (TKI) Lapatinib anti-HER2 biodrugs. We show that exosomes released by the HER2-overexpressing tumor cell lines SKBR3 and BT474 express a full-length HER2 molecule that is also activated, although to a lesser extent than in the originating cells. Release of these exosomes was significantly modulated by the growth factors EGF and heregulin, two of the known HER2 receptor-activating ligands and naturally present in the surrounding tumor microenvironment. Exosomes secreted either in HER2-positive tumor cell-conditioned supernatants or in breast cancer patients' serum bound to Trastuzumab. Functional assays revealed that both xenogeneic and autologous HER2-positive nanovesicles, but not HER2-negative ones, inhibited Trastuzumab activity on SKBR3 cell proliferation. By contrast, Lapatinib activity on SKBR3 cell proliferation was unaffected by the presence of autologous exosomes. Together, these findings point to the role of HER2-positive exosomes in modulating sensitivity to Trastuzumab, and, consequently, to HER2-driven tumor aggressiveness.     

Studying the effects of laccase-catalysed grafting of ferulic acid on sisal pulp fibers

Functionalization of sisal specialty pulp fibers by laccase-catalysed grafting of ferulic acid (FRC) was investigated. To this end, the extent of phenol coupling to fibers under different reaction conditions (laccase and FRC rates, and time) was evaluated in terms of pulp properties including kappa number (expressed as the combined contributions of lignin and hexenuronic acids), brightness, Klason lignin and surface anionic charge after Soxhlet extraction of acetone-treated pulp. The specific treatment resulting in the highest degree of grafting was then used in a comparative study of the effects of applying the laccase-FRC system to refined and unrefined pulp with a view to confirming whether the increased surface area obtained by effect of fibrillation would lead to enhanced grafting. Based on the results, refining the pulp prior to the enzyme treatment resulted in increased grafting which in turn led to handsheets with improved strength-related properties (particularly wet tensile strength) relative to control samples.