Jack-of-all-trades and master of many? How does associated rhizobial diversity influence the colonization success of Australian Acacia species?

Aim To evaluate the role of rhizobial diversity, and symbiotic promiscuity, on the invasive ability of Australian acacias (Acacia species in subgenus Phyllodineae native to Australia). Location Global. Methods A bibliographic review of the rhizobial diversity associated with Australian Acacia species was performed to assess symbiotic promiscuity for invasive and non-invasive species. The rhizobial diversity associated with Acacia dealbata and A. saligna in Australia and Portugal and with A. pycnantha in Australia and South Africa was assessed by 16S rDNA and intergenic spacer sequencing of bacteria isolated from field-collected nodules. Results All studied Australian acacias are nodulated by strains in the genus Bradyrhizobium, which appears to be the dominant group of acacia symbionts in native and non-native soils. Both literature and experimental data from this study suggest that Australian bradyrhizobia might have been co-introduced with acacias to new geographical regions. The studied Acacia species can also harbour other root-nodulating alpha and betaproteobacteria genera, although these are less abundant than Bradyrhizobium. Main conclusions There is no clear difference in the diversity of rhizobial species associated with invasive and non-invasive Australian acacias. All studied invasive acacias nodulate in both native and non-native regions, harbouring predominantly Bradyrhizobium strains but showing some degree of symbiotic promiscuity. The co-introduction of compatible root-nodulating bacteria from Australia might explain the establishment of invasive populations, but novel associations with rhizobia from the invaded soils are also possible. Invasive legumes might use both strategies but species with low symbiotic promiscuity would become invasive only if compatible bacteria are co-introduced in the new regions. The progress of invasion and the impacts on the invaded ecosystems might also differ depending on the nodulation strategy.Centre of Excellence for Invasion Biolog

PET myocardial perfusion quantification: anatomy of a spreading functional technique

Purpose To summarize the physical principles, imaging method, available tools for and the clinical value of quantitative perfusion evaluation with cardiac PET as well as future aims in the field in a narrative review.Results Cardiac positron-emission tomography (PET) currently constitutes the reference standard for non-invasive quantitative evaluation of myocardial blood flow. This added modality provides useful information beyond standard semi-quantitative myocardial perfusion evaluation. A description of how the different phases of PET studies are interpreted is provided, as well as a short depiction of the most commonly used radiotracers and the main characteristics affecting their clinical utility. The diagnostic and prognostic utility concerning myocardial perfusion quantified in absolute terms is discussed and the additional contribution of the increasingly spread hybrid equipment is summarized.Conclusion PET myocardial perfusion represents an excellent noninvasive technique for the evaluation of known or suspected ischemic heart disease, and its clinical application should widen in the near future. The clinical value of PET quantitative perfusion is expected to improve patient outcomes and optimize therapeutic decisions, which constitute key elements for the future of cardiovascular medicine

Development of transgenic rats producing human β-amyloid precursor protein as a model for Alzheimer's disease: Transgene and endogenous APP genes are regulated tissue-specifically

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects a large and growing number of elderly individuals. In addition to idiopathic disease, AD is also associated with autosomal dominant inheritance, which causes a familial form of AD (FAD). Some instances of FAD have been linked to mutations in the β-amyloid protein precursor (APP). Although there are numerous mouse AD models available, few rat AD models, which have several advantages over mice, have been generated.</p> <p>Results</p> <p>Fischer 344 rats expressing human APP driven by the ubiquitin-C promoter were generated via lentiviral vector infection of Fischer 344 zygotes. We generated two separate APP-transgenic rat lines, APP21 and APP31. Serum levels of human amyloid-beta (Aβ)₄₀were 298 pg/ml for hemizygous and 486 pg/ml for homozygous APP21 animals. Serum Aβ₄₂levels in APP21 homozygous rats were 135 pg/ml. Immunohistochemistry in brain showed that the human APP transgene was expressed in neurons, but not in glial cells. These findings were consistent with independent examination of enhanced green fluorescent protein (eGFP) in the brains of eGFP-transgenic rats. APP21 and APP31 rats expressed 7.5- and 3-times more APP mRNA, respectively, than did wild-type rats. Northern blots showed that the human APP transgene, driven by the ubiquitin-C promoter, is expressed significantly more in brain, kidney and lung compared to heart and liver. A similar expression pattern was also seen for the endogenous rat APP. The unexpected similarity in the tissue-specific expression patterns of endogenous rat APP and transgenic human APP mRNAs suggests regulatory elements within the cDNA sequence of APP.</p> <p>Conclusion</p> <p>This manuscript describes the generation of APP-transgenic inbred Fischer 344 rats. These are the first human AD model rat lines generated by lentiviral infection. The APP21 rat line expresses high levels of human APP and could be a useful model for AD. Tissue-specific expression in the two transgenic rat lines and in wild-type rats contradicts our current understanding of APP gene regulation. Determination of the elements that are responsible for tissue-specific expression of APP may enable new treatment options for AD.</p

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival

Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130±27.6% (P<0.05) similar to that induced by VEGF and with which it is additive (281±13%) (P<0.05). Moreover, specific blockade of the receptor (either by α IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours

Effectiveness of Protease Inhibitor Monotherapy versus Combination Antiretroviral Maintenance Therapy: A Meta-Analysis

The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs

Systems approaches to innovation in crop protection. A systematic literature review

The objective of this paper is to explore the extent to which systems approaches to innovation are reflected in the crop protection literature and how such approaches are used. A systematic literature review is conducted to study the relation between crop protection and systems approaches to innovation in 107 publications. The analysis of the crop protection literature demonstrates that only a small fraction is systems-oriented as compared to the bulk of publications with a technology-oriented approach. The analysis of agricultural innovations systems literature shows that, although crop protection is addressed, the potential of this systems approach remains largely unexplored for crop protection innovation. A large share of the publications included in this review focus on cropping or farming ‘systems’ while ‘innovation’ often equals the development, transfer, adoption and diffusion of crop protection technologies at farm level. There is relatively little attention for the institutional and political dimensions of crop protection and the interactions between farm, regional and national levels in crop protection systems. The traditional division of roles and responsibilities of researchers as innovators, extension personnel as disseminators, and farmers as end-users, is challenged only to a limited extent. The majority of publications discusses ways to optimise existing features of crop protection systems, without exploring more structural transformations that may be required to enhance the resilience of crop protection systems

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.