Proteome Regulation during Olea europaea Fruit Development

Widespread in the Mediterranean basin, Olea europaea trees are gaining worldwide popularity for the nutritional and cancer-protective properties of the oil, mechanically extracted from ripe fruits. Fruit development is a physiological process with remarkable impact on the modulation of the biosynthesis of compounds affecting the quality of the drupes as well as the final composition of the olive oil. Proteomics offers the possibility to dig deeper into the major changes during fruit development, including the important phase of ripening, and to classify temporal patterns of protein accumulation occurring during these complex physiological processes.In this work, we started monitoring the proteome variations associated with olive fruit development by using comparative proteomics coupled to mass spectrometry. Proteins extracted from drupes at three different developmental stages were separated on 2-DE and subjected to image analysis. 247 protein spots were revealed as differentially accumulated. Proteins were identified from a total of 121 spots and discussed in relation to olive drupe metabolic changes occurring during fruit development. In order to evaluate if changes observed at the protein level were consistent with changes of mRNAs, proteomic data produced in the present work were compared with transcriptomic data elaborated during previous studies.This study identifies a number of proteins responsible for quality traits of cv. Coratina, with particular regard to proteins associated to the metabolism of fatty acids, phenolic and aroma compounds. Proteins involved in fruit photosynthesis have been also identified and their pivotal contribution in oleogenesis has been discussed. To date, this study represents the first characterization of the olive fruit proteome during development, providing new insights into fruit metabolism and oil accumulation process

Inhibition of Neuroblastoma Tumor Growth by Targeted Delivery of MicroRNA-34a Using Anti-Disialoganglioside GD2 Coated Nanoparticles

Neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in paediatric oncology, underlining the need for novel therapeutic approaches. Typically, patients with high risk disease undergo an initial remission in response to treatment, followed by disease recurrence that has become refractory to further treatment. Here, we demonstrate the first silica nanoparticle-based targeted delivery of a tumor suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine orthotopic xenograft model. These tumors express high levels of the cell surface antigen disialoganglioside GD2 (GD(2)), providing a target for tumor-specific delivery.Nanoparticles encapsulating miR-34a and conjugated to a GD(2) antibody facilitated tumor-specific delivery following systemic administration into tumor bearing mice, resulted in significantly decreased tumor growth, increased apoptosis and a reduction in vascularisation. We further demonstrate a novel, multi-step molecular mechanism by which miR-34a leads to increased levels of the tissue inhibitor metallopeptidase 2 precursor (TIMP2) protein, accounting for the highly reduced vascularisation noted in miR-34a-treated tumors.These novel findings highlight the potential of anti-GD(2)-nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD(2)-expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth

The airbag problem-a potential culprit for bench-to-bedside translational efforts: relevance for Alzheimer's disease

For the last 20 years, the "amyloid cascade hypothesis" has dominated research aimed at understanding, preventing, and curing Alzheimer's disease (AD). During that time researchers have acquired an enormous amount of data and have been successful, more than 300 times, in curing the disease in animal model systems by treatments aimed at clearing amyloid deposits. However, to date similar strategies have not been successful in human AD patients. Hence, before rushing into further clinical trials with compounds that aim at lowering amyloid-beta (Aβ) levels in increasingly younger people, it would be of highest priority to re-assess the initial assumption that accumulation of Aβ in the brain is the primary pathological event driving AD. Here we question this assumption by highlighting experimental evidence in support of the alternative hypothesis suggesting that APP and Aβ are part of a neuronal stress/injury system, which is up-regulated to counteract inflammation/oxidative stress-associated neurodegeneration that could be triggered by a brain injury, chronic infections, or a systemic disease. In AD, this protective program may be overridden by genetic and other risk factors, or its maintenance may become dysregulated during aging. Here, we provide a hypothetical example of a hypothesis-driven correlation between car accidents and airbag release in analogy to the evolution of the amyloid focus and as a way to offer a potential explanation for the failure of the AD field to translate the success of amyloid-related therapeutic strategies in experimental models to the clinic

Suppressing Stick-Slip Oscillations in Oilwell Drillstrings

International audienceIn drilling operations, the drillstring interaction with the borehole gives rise to a wide variety of non-desired oscillations. The main types of drilling vibrations are torsional (stick-slip), axial (bit-bounce) and lateral (whirling). The analysis and modeling of rotary drilling vibrations is a topic whose economical interest has been renewed by recent oil fields discoveries leading to a growing literature. This contribution addresses the problem of modeling and control of the most critical vibration mode: the stick-slip phenomenon. The wave equation subject to mixed boundary conditions is used to reproduce torsional oscillations of the drillstring. By means of a direct transformation we derive an input-output model described by a neutral-type time-delay equation which clearly simplifies the system simulation. A dissipativity analysis of the wave equation model leads to the design of a stabilizing controller guaranteeing a non-growth of energy during the drilling process. Furthermore, by means of a polytopic representation of the neutral-type time-delay model, stability and stabilization conditions in terms of Linear Matrix Inequalities (LMIs) are given. The performance of the proposed approaches is highlighted through simulations showing an effective suppression of the stick-slip phenomenon

Onset of grain filling is associated with a change in properties of linker histone variants in maize kernels

In maize kernel development, the onset of grain-filling represents a major developmental switch that correlates with a massive reprogramming of gene expression. We have isolated chromosomal linker histones from developing maize kernels before (11 days after pollination, dap) and after (16 dap) initiation of storage synthesis. Six linker histone gene products were identified by MALDI-TOF mass spectrometry. A marked shift of around 4 pH units was observed for the linker histone spot pattern after 2D-gel electrophoresis when comparing the proteins of 11 and 16 dap kernels. The shift from acidic to more basic protein forms suggests a reduction in the level of post-translational modifications of linker histones during kernel development. Analysis of their DNA-binding affinity revealed that the different linker histone gene products bind double-stranded DNA with similar affinity. Interestingly, the linker histones isolated from 16 dap kernels consistently displayed a lower affinity for DNA than the proteins isolated from 11 dap kernels. These findings suggest that the affinity for DNA of the linker histones may be regulated by post-translational modification and that the reduction in DNA affinity could be involved in a more open chromatin during storage synthesis