Invasive Diseases and Fruit Tree Production: Economic Tradeoffs of Citrus Greening Control on Florida's Citrus Industry

An investment model of Florida oranges was used to evaluate various management strategies for controlling Huanglongbing, or citrus greening, a highly destructive disease. This analysis will enable the Florida citrus industry to make more informed decisions about the economic tradeoffs among current citrus greening management alternatives.Crop Production/Industries,

Pharmacokinetics of adrenaline autoinjectors.

Anaphylaxis is a medical emergency with adrenaline acknowledged as the first line therapy. It is therefore important that patients have access to self-injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators' websites and freedom of information requests. The data demonstrate that it takes at least 5-10 minutes to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time-to-peak concentration longer with increased skin-to-muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head-to-head comparisons, small numbers of study participants, and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes

Prioritisation and Network Analysis of Crohn's Disease Susceptibility Genes

Recent Genome-Wide Association Studies (GWAS) have revealed numerous Crohn's disease susceptibility genes and a key challenge now is in understanding how risk polymorphisms in associated genes might contribute to development of this disease. For a gene to contribute to disease phenotype, its risk variant will likely adversely communicate with a variety of other gene products to result in dysregulation of common signaling pathways. A vital challenge is to elucidate pathways of potentially greatest influence on pathological behaviour, in a manner recognizing how multiple relevant genes may yield integrative effect. In this work we apply mathematical analysis of networks involving the list of recently described Crohn's susceptibility genes, to prioritise pathways in relation to their potential development of this disease. Prioritisation was performed by applying a text mining and a diffusion based method (GRAIL, GPEC). Prospective biological significance of the resulting prioritised list of proteins is highlighted by changes in their gene expression levels in Crohn's patients intestinal tissue in comparison with healthy donors.United States. Army Research Office (Institute for Collaborative Biotechnologies Contract W911NF-09-D-0001

Pumilio binds para mRNA and requires nanos and brat to regulate sodium current in drosophila motoneurons

Homeostatic regulation of ionic currents is of paramount importance during periods of synaptic growth or remodeling. Our previous work has identified the translational repressor Pumilio (Pum) as a regulator of sodium current (INa) and excitability in Drosophila motoneurons. In this current study, we show that Pum is able to bind directly the mRNA encoding the Drosophila voltage-gated sodium channel paralytic (para). We identify a putative binding site for Pum in the 3' end of the para open reading frame (ORF). Characterization of the mechanism of action of Pum, using whole-cell patch clamp and real-time reverse transcription-PCR, reveals that the full-length protein is required for translational repression of para mRNA. Additionally, the cofactor Nanos is essential for Pum-dependent para repression, whereas the requirement for Brain Tumor (Brat) is cell type specific. Thus, Pum-dependent regulation of INa in motoneurons requires both Nanos and Brat, whereas regulation in other neuronal types seemingly requires only Nanos but not Brat. We also show that Pum is able to reduce the level of nanos mRNA and as such identify a potential negative-feedback mechanism to protect neurons from overactivity of Pum. Finally, we show coupling between INa (para) and IK (Shal) such that Pum-mediated change in para results in a compensatory change in Shal. The identification of para as a direct target of Pum represents the first ion channel to be translationally regulated by this repressor and the location of the binding motif is the first example in an ORF rather than in the canonical 3'-untranslated region of target transcripts

1H-NMR plasma lipoproteins profile analysis reveals lipid metabolism alterations in HER2-positive breast cancer patients

The lipid tumour demand may shape the host metabolism adapting the circulating lipids composition to its growth and progression needs. This study aims to exploit the straightforward 1 H-NMR lipoproteins analysis to investigate the alterations of the circulating lipoproteins’ fractions in HER2-positive breast cancer and their modulations induced by treatments. The baseline1H-NMR plasma lipoproteins profiles were measured in 43 HER2-positive breast cancer patients and compared with those of 28 healthy women. In a subset of 32 patients, longitudinal measurements were also performed along neoadjuvant chemotherapy, after surgery, adjuvant treatment, and during the two-year follow-up. Differences between groups were assessed by multivariate PLS-DA and by univariate analyses. The diagnostic power of lipoproteins subfractions was assessed by ROC curve, while lipoproteins time changes along interventions were investigated by ANOVA analysis. The PLS-DA model distinguished HER2-positive breast cancer patients from the control group with a sensitivity of 96.4% and specificity of 90.7%, mainly due to the differential levels of VLDLs subfractions that were significantly higher in the patients' group. Neoadjuvant chemotherapy-induced a significant drop in the HDLs after the first three months of treatment and a specific decrease in the HDL-3 and HDL-4 subfractions were found significantly associated with the pathological complete response achievement. These results indicate that HER2-positive breast cancer is characterized by a significant host lipid mobilization that could be useful for diagnostic purposes. Moreover, the lipoproteins profiles alterations induced by the therapeutic interventions could predict the clinical outcome supporting the application of1H-NMR lipoproteins profiles analysis for longitudinal monitoring of HER2-positive breast cancer in large clinical studies

Development of oral immunomodulatory agents in the management of multiple sclerosis

The emergence of oral disease-modifying therapies in multiple sclerosis (MS) will have a significant impact on the evolving scenario of immunomodulatory treatments in MS where current therapies are all injectable. Reducing relapses in trials translates for individuals with MS into a therapeutic aim of stopping future events. Thus the possible absence of any perceived benefits to the individual together with the long disease course, variable outcome, and a younger age group affected in MS makes side effects the major issue. The use of disease-modifying therapies as a whole needs to be placed in the context of a widening therapeutic indication where the use of these therapies is being justified at an increasingly early stage and in pre-MS syndromes such as clinically isolated and radiologically isolated syndromes where no fixed disability is likely to have accumulated. The five oral therapies discussed (cladribine, fingolimod, laquinimod, BG-12, and teriflunomide) have just completed Phase III studies and some have just been licensed. New oral drugs for MS need to be placed within this evolving marketplace where ease of delivery together with efficacy and side effects needs to be balanced against the known issues but also the known long-term safety of standard injectables

In-room test results at CNAO of an innovative PT treatments online monitor (Dose Profiler)

The use of C, He and O ions as projectiles in Particle Therapy (PT) treatments is getting more and more widespread as a consequence of their enhanced relative biological effectiveness and oxygen enhancement ratio, when compared to the protons one. The advantages related to the incoming radiation improved efficacy are requiring an accurate online monitor of the dose release spatial distribution. Such monitor is necessary to prevent unwanted damage to the tissues surrounding the tumour that can arise, for example, due to morphological changes occurred in the patient during the treatment with respect to the initial CT scan. PT treatments with ions can be monitored by detecting the secondary radiation produced by the primary beam interactions with the patient body along the path towards the target volume. Charged fragments produced in the nuclear process of projectile fragmentation can be emitted at large angles with respect to the incoming beam direction and can be detected with high efficiency in a nearly background-free environment. The Dose Profiler (DP) detector, developed within the INSIDE project, is a scintillating fibre tracker that allows an online reconstruction and backtracking of such secondary charged fragments. The construction and preliminary in-room tests performed on the DP, carried out using the 12C ions beam of the CNAO treatment centre using an anthropomorphic phantom as a target, will be reviewed in this contribution. The impact of the secondary fragments interactions with the patient body will be discussed in view of a clinical application. Furthermore, the results implications for a pre-clinical trial on CNAO patients, foreseen in 2019, will be discussed