Modification de la biodistribution non tumorale du 18FMISO,un traceur d’hypoxie,chez les patients traités par sunitinib pour cancer du rein métastatique

ObjectiveThe purpose of the study was to find the potential impact of the sunitinib on the captation of a tracer of the hypoxia, ¹⁸F-FMISO, on non tumoral tissues.Population and methodsIt was about a multicentric prospective study on 43 patients with advanced or metastatic renal cancer, treated with Sunitinib. ¹⁸F-FMISO PET/CT scan was performed before treatment, followed with a second PET/CT scan after 4 weeks of treatment with sunitinib.ResultsWe have shown a significant increase of FMISO captation under sunitinib in the lungs (p < 0.02) and the liver (p < 0.001). We have also found a significant increase of FMISO captation under antiangiogenic (p < 0.02) of the arterial wall partially calcified among 23/37 patients reached of atherosclerosis, without notable cardiovascular events in the follow-up of these patients. On the other hand, we highlighted a significant reduction of FMISO captation in arthrosic lesions (p < 0.05).Conclusion¹⁸F-FMISO PET/CT scan could be a good indicator of the potential toxicities of sunitinib, in particular the pulmonary, hepatic and cardiovascular side effects. It also shows the potential interest of antiangiogenic in inflammatory rheumatic diseases.     

Overexpression of arginase in the aged mouse penis impairs erectile function and decreases eNOS activity: influence of in vivo gene therapy of anti-arginase

Since both increased nitric oxide (NO) synthase (NOS) abundance and diminished NO signaling have been reported in the aging penis, the role of NO in the adaptations of aging remains controversial. Here we tested the hypothesis that arginase, an enzyme that competes with NOS for the substrate l-arginine, contributes to erectile dysfunction with advanced age in the B6/129 mouse strain. Arginase protein abundance, mRNA expression, and enzyme activity were elevated in aged compared with young penile endothelial cells. In addition, endothelial NOS (NOS3) protein abundance was greater in aged versus young penile endothelial cells, whereas NOS activity and cGMP levels were reduced. Calcium-dependent l-arginine-to-l-citrulline conversion and cGMP formation increased significantly in aged mouse penes in the presence of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH). However, there was no effect on l-arginine-to-l-citrulline conversion or cGMP accumulation in the endothelium from young mouse penes. To assess the functional role of arginase in the inhibition of NOS pathway responsiveness in the penis, we evaluated the effects of ABH and an adeno-associated virus encoding an antisense sequence to arginase I (AAVanti-arginase) on erectile function in vivo. ABH and AAVanti-arginase enhanced endothelium-dependent erectile responses in the aged mice without altering endothelium-independent responses. Paralleling our in vitro observations, ABH or AAVanti-arginase did not affect vascular responses in the young mice. Inhibition of the arginase pathway improves endothelial function in the aging penile circulation, suggesting that the arginase pathway may be exploited to improve erectile dysfunction associated with aging.     

The 9-lipoxygenase GhLOX1 gene is associated with the hypersensitive reaction of cotton Gossypium hirsutum to Xanthomonas campestris pv malvacearum.

Hypersensitive reaction (HR) cell death of cotton to the incompatible race 18 from Xanthomonas campestris pathovar malvacearum (Xcm) is associated with 9S-lipoxygenase activity (LOX) responsible for lipid peroxidation. Here, we report the cloning of cotton (Gossypium hirsutum L.) LOX gene (GhLOX1) and the sequencing of its promoter. GhLOX1 was found to be highly expressed during Xcm induced HR. Sequence analysis showed that GhLOX1 is a putative 9-LOX, and GhLOX1 promoter contains SA and JA responsive elements. Investigation on LOX signalisation on cotyledons infiltrated with salicylic acid (SA), or incubated with methyl-jasmonate (MeJA) revealed that both treatments induced LOX activity and GhLOX1 gene expression. HR-like symptoms were observed when LOX substrates were then injected in treated (MeJA and SA) cotyledons or when Xcm compatible race 20 was inoculated on MeJA treated cotyledons. Together these results support the fact that GhLOX1 encodes a 9 LOX whose activity would be involved in cell death during cotton HR.     

Structural Relaxation During Drying and Rehydration of Food Materials��the Water Effect and the Origin of Hysteresis

The state of water in foodstuffs is a guiding principle in food design, and the equilibrium concept of water activity (Aw) is ubiquitous. It is regarded as a primary variable or “hurdle” in preservation technology, and a key variable influencing chemical reaction during storage. However, the amount of water in any system differs as function of water activity depending whether it is determined by water sorption or desorption. Even though this hysteresis behaviour has already been described in the literature, no physical interpretation of its origin has yet been proposed with respect to detailed molecular organisation. This work shows, for two different food powders, gluten and a milk-based product that the hysteresis disappears when either go through their glass transition. A more complete DSC analysis for gluten during different sorption/desorption cycles demonstrates that the hysteresis is dependent on the ageing of the material, which evolves in the glassy state and is induced by structural relaxation.     

Spiraled origins

Recent studies have established that the eukaryotic actin-based cytoskeleton has prokaryotic origins. In addition to regulating cell shape and polarity, Gitai et al. (2005) provide convincing evidence that the Caulobacter actin homolog MreB also mediates the early segregation of the chromosomal origin, a typical functional role of the eukaryotic tubulin-based cytoskeleton.     

Effects of successive seasons of genetically modified herbicide-tolerant maize cropping on weeds and invertebrates

The use of genetically modified herbicide‐tolerant (GMHT) crops influences the abundance of weeds and some invertebrate groups because the associated herbicide regime contrasts with that of conventional systems. However, it is not clear to what extent these effects might be cumulative; should GMHT crops be grown continuously. In northern Europe, in the near future, this situation is most likely to apply to maize crops. Here, we consider the effects of continuous GMHT maize cropping on plant and invertebrate taxa using a split‐field experiment. Half of each field was managed using GMHT and the other half with a conventional variety, with the treatments retained for two seasons. The treatment effects were broadly consistent with those found in the larger sample of non‐continuous maize sites within the Farm Scale Evaluations. There was little evidence of effects being significantly more pronounced in the second year; any cumulative differences in above‐ground biodiversity between GMHT and conventional cropping were too variable to be readily detected.     

Visual extrapolation under risk: human observers estimate and compensate for exogenous uncertainty

Humans commonly face choices between multiple options with uncertain outcomes. Such situations occur in many contexts, from purely financial decisions (which shares should I buy?) to perceptuo-motor decisions between different actions (where should I aim my shot at goal?). Regardless of context, successful decision-making requires that the uncertainty at the heart of the decision-making problem is taken into account. Here, we ask whether humans can recover an estimate of exogenous uncertainty and then use it to make good decisions. Observers viewed a small dot that moved erratically until it disappeared behind an occluder. We varied the size of the occluder and the unpredictability of the dot''s path. The observer attempted to capture the dot as it emerged from behind the occluded region by setting the location and extent of a ‘catcher’ along the edge of the occluder. The reward for successfully catching the dot was reduced as the size of the catcher increased. We compared human performance with that of an agent maximizing expected gain and found that observers consistently selected catcher size close to this theoretical solution. These results suggest that humans are finely tuned to exogenous uncertainty information and can exploit it to guide action.     

Vault nanocapsules as adjuvants favor cell-mediated over antibody-mediated immune responses following immunization of mice

Background

Modifications of adjuvants that induce cell-mediated over antibody-mediated immunity is desired for development of vaccines. Nanocapsules have been found to be viable adjuvants and are amenable to engineering for desired immune responses. We previously showed that natural nanocapsules called vaults can be genetically engineered to elicit Th1 immunity and protection from a mucosal bacterial infection. The purpose of our study was to characterize immunity produced in response to OVA within vault nanoparticles and compare it to another nanocarrier.

Methodology and Principal Findings

We characterized immunity resulting from immunization with the model antigen, ovalbumin (OVA) encased in vault nanocapsules and liposomes. We measured OVA responsive CD8⁺ and CD4⁺ memory T cell responses, cytokine production and antibody titers in vitro and in vivo. We found that immunization with OVA contain in vaults induced a greater number of anti-OVA CD8⁺ memory T cells and production of IFNγ plus CD4⁺ memory T cells. Also, modification of the vault body could change the immune response compared to OVA encased in liposomes.

Conclusions/Significance

These experiments show that vault nanocapsules induced strong anti-OVA CD8⁺ and CD4⁺ T cell memory responses and modest antibody production, which markedly differed from the immune response induced by liposomes. We also found that the vault nanocapsule could be modified to change antibody isotypes in vivo. Thus it is possible to create a vault nanocapsule vaccine that can result in the unique combination of immunogen-responsive CD8⁺ and CD4⁺ T cell immunity coupled with an IgG1 response for future development of vault nanocapsule-based vaccines against antigens for human pathogens and cancer.     

A direct interaction between the Utp6 half-a-tetratricopeptide repeat domain and a specific peptide in Utp21 is essential for efficient pre-rRNA processing

The small subunit (SSU) processome is a ribosome biogenesis intermediate that assembles from its subcomplexes onto the pre-18S rRNA with yet unknown order and structure. Here, we investigate the architecture of the UtpB subcomplex of the SSU processome, focusing on the interaction between the half-a-tetratricopeptide repeat (HAT) domain of Utp6 and a specific peptide in Utp21. We present a comprehensive map of the interactions within the UtpB subcomplex and further show that the N-terminal domain of Utp6 interacts with Utp18 while the HAT domain interacts with Utp21. Using a panel of point and deletion mutants of Utp6, we show that an intact HAT domain is essential for efficient pre-rRNA processing and cell growth. Further investigation of the Utp6-Utp21 interaction using both genetic and biophysical methods shows that the HAT domain binds a specific peptide ligand in Utp21, the first example of a HAT domain peptide ligand, with a dissociation constant of 10 μM.