Decomposers and root feeders interactively affect plant defence in Sinapis alba

Aboveground herbivory is well known to change plant growth and defence. In contrast, effects of soil organisms, acting alone or in concert, on allocation patterns are less well understood. We investigated separate and combined effects of the endogeic earthworm species Aporrectodea caliginosa and the root feeding nematode species Pratylenchus penetrans and Meloidogyne incognita on plant responses including growth and defence metabolite concentrations in leaves of white mustard, Sinapis alba. Soil biota had a strong impact on plant traits, with the intensity varying due to species combinations. Nematode infestation reduced shoot biomass and nitrogen concentration but only in the absence of earthworms. Earthworms likely counteracted the negative effects of nematodes. Infestation with the migratory lesion-nematode P. penetrans combined with earthworms led to increased root length. Earthworm biomass increased in the presence of this species, indicating that these nematodes increased the food resources of earthworms—presumably dead and decaying roots. Nitrogen-based defence compounds, i.e. glucosinolates, did not correlate with nitrogen levels. In the presence of earthworms, concentrations of aromatic glucosinolates in leaves were significantly increased. In contrast, infection with P. penetrans strongly decreased concentrations of glucosinolates (up to 81%). Infestation with the sedentary nematode M. incognita induced aromatic glucosinolates by more than 50% but only when earthworms were also present. Myrosinase activities, glucosinolate-hydrolysing enzymes, were unaffected by nematodes but reduced in the presence of earthworms. Our results document that root-feeding nematodes elicit systemic plant responses in defence metabolites, with the responses varying drastically with nematode species of different functional groups. Furthermore, systemic plant responses are also altered by decomposer animals, such as earthworms, challenging the assumption that induction of plant responses including defence traits is restricted to herbivores. Soil animals even interact and modulate the individual effects on plant growth and plant defence, thereby likely also influencing shoot herbivore attack

The growth of a culture of evidence-based obstetrics in South Africa: a qualitative case study

<p>Abstract</p> <p>Background</p> <p>While the past two decades have seen a shift towards evidence-based obstetrics and midwifery, the process through which a culture of evidence-based practice develops and is sustained within particular fields of clinical practice has not been well documented, particularly in LMICs (low- and middle-income countries). Forming part of a broader qualitative study of evidence-based policy making, this paper describes the development of a culture of evidence-based practice amongst maternal health policy makers and senior academic obstetricians in South Africa</p> <p>Methods</p> <p>A qualitative case-study approach was used. This included a literature review, a policy document review, a timeline of key events and the collection and analysis of 15 interviews with policy makers and academic clinicians involved in these policy processes and sampled using a purposive approach. The data was analysed thematically.</p> <p>Results</p> <p>The concept of evidence-based medicine became embedded in South African academic obstetrics at a very early stage in relation to the development of the concept internationally. The diffusion of this concept into local academic obstetrics was facilitated by contact and exchange between local academic obstetricians, opinion leaders in international research and structures promoting evidence-based practice. Furthermore the growing acceptance of the concept was stimulated locally through the use of existing professional networks and meetings to share ideas and the contribution of local researchers to building the evidence base for obstetrics both locally and internationally. As a testimony to the extent of the diffusion of evidence-based medicine, South Africa has strongly evidence-based policies for maternal health.</p> <p>Conclusion</p> <p>This case study shows that the combined efforts of local and international researchers can create a culture of evidence-based medicine within one country. It also shows that doing so required time and perseverance from international researchers combined with a readiness by local researchers to receive and actively promote the practice.</p

Transcriptional and Post-Transcriptional Regulation of SPAST, the Gene Most Frequently Mutated in Hereditary Spastic Paraplegia

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70–80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ∼10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3′-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP

Clinical burden of illness among patients with severe eosinophilic COPD

Hana M&uuml;llerov&aacute;,1 Wilhelmine H Meeraus,1 Dmitry V Galkin,2 Frank C Albers,2 Sarah H Landis1,31Respiratory Epidemiology, GSK, Uxbridge, UK; 2Respiratory Medical Franchise, GSK, Uxbridge, NC, USA; 3Patient Centered Outcomes and Value Evidence and Outcomes, GSK, Collegeville, PA, USABackground: There are currently limited real-world data on the clinical burden of illness in patients with COPD who continue to exacerbate despite receiving triple therapy. The aim of this study was to compare the burden of COPD in patients with and without a phenotype characterized by a high blood eosinophil count and high risk of exacerbations while receiving triple therapy.Methods: This retrospective cohort study (GSK ID: 207323/PRJ2647) used UK Clinical Practice Research Datalink records linked with Hospital Episode Statistics. Eligible patients had a COPD medical diagnosis code recorded between January 1, 2004 and December 31, 2014, and a blood eosinophil count recorded on/after that date. Patients were followed from index date (first qualifying blood eosinophil count) until December 31, 2015. The study phenotype was defined as &ge;2 moderate/&ge;1 severe acute exacerbation of COPD (AECOPD) in the year prior to the index date, current use of multiple-inhaler triple therapy (MITT), and blood eosinophil count &ge;150 cells/&mu;L on the index date. Outcomes measured during follow-up included moderate/severe AECOPDs, severe AECOPDs, all-cause mortality, primary care (GP) clinical consultations, and non-AECOPD-related unscheduled hospitalizations.Results: Of 46,814 patients eligible for inclusion, 2512 (5.4%) met the definition of the study phenotype. Adjusted rate ratios (95% CI) of moderate/severe AECOPDs and all-cause mortality in patients with the study phenotype versus those without were 2.32 (2.22, 2.43) and 1.26 (1.16, 1.37), respectively. For GP visits and non-AECOPD-related unscheduled hospitalizations, adjusted rate ratios (95% CI), in patients with the study phenotype versus those without, were 1.09 (1.05, 1.12) and 1.31 (1.18, 1.46), respectively.Conclusion: Patients with COPD and raised blood eosinophil counts who continue to exacerbate despite MITT represent a distinct subgroup who experience substantial clinical burden and account for high healthcare expenditure. There is a need for more effective management and therapeutic options for these patients.Keywords: acute exacerbations, burden of illness, eosinophils, multiple-inhaler triple therap

Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome

Item does not contain fulltextThe exon-junction complex (EJC) performs essential RNA processing tasks. Here, we describe the first human disorder, thrombocytopenia with absent radii (TAR), caused by deficiency in one of the four EJC subunits. Compound inheritance of a rare null allele and one of two low-frequency SNPs in the regulatory regions of RBM8A, encoding the Y14 subunit of EJC, causes TAR. We found that this inheritance mechanism explained 53 of 55 cases (P < 5 x 10(-228)) of the rare congenital malformation syndrome. Of the 53 cases with this inheritance pattern, 51 carried a submicroscopic deletion of 1q21.1 that has previously been associated with TAR, and two carried a truncation or frameshift null mutation in RBM8A. We show that the two regulatory SNPs result in diminished RBM8A transcription in vitro and that Y14 expression is reduced in platelets from individuals with TAR. Our data implicate Y14 insufficiency and, presumably, an EJC defect as the cause of TAR syndrome