A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

Observation of absorbing aerosols above clouds over the south-east Atlantic Ocean from the geostationary satellite SEVIRI – Part 1: Method description and sensitivity

This is the final version. Available on open access from EGU via the DOI in this recordData availability: The data used for this study are available from the corresponding author, FP, upon reasonable request.High-temporal-resolution observations from satellites have a great potential for studying the impact of biomass burning aerosols and clouds over the south-east Atlantic Ocean (SEAO). This paper presents a method developed to simultaneously retrieve aerosol and cloud properties in aerosol above-cloud conditions from the geostationary instrument Meteosat Second Generation/Spinning Enhanced Visible and Infrared Imager (MSG/SEVIRI). The above-cloud aerosol optical thickness (AOT), the cloud optical thickness (COT) and the cloud droplet effective radius (CER) are derived from the spectral contrast and the magnitude of the signal measured in three channels in the visible to shortwave infrared region. The impact of the absorption from atmospheric gases on the satellite signal is corrected by applying transmittances calculated using the water vapour profiles from a Met Office forecast model. The sensitivity analysis shows that a 10 % error on the humidity profile leads to an 18.5 % bias on the above-cloud AOT, which highlights the importance of an accurate atmospheric correction scheme. In situ measurements from the CLARIFY-2017 airborne field campaign are used to constrain the aerosol size distribution and refractive index that is assumed for the aforementioned retrieval algorithm. The sensitivities in the retrieved AOT, COT and CER to the aerosol model assumptions are assessed. Between 09:00 and 15:00 UTC, an uncertainty of 40 % is estimated on the above-cloud AOT, which is dominated by the sensitivity of the retrieval to the single-scattering albedo. The absorption AOT is less sensitive to the aerosol assumptions with an uncertainty generally lower than 17 % between 09:00 and 15:00 UTC. Outside of that time range, as the scattering angle decreases, the sensitivity of the AOT and the absorption AOT to the aerosol model increases. The retrieved cloud properties are only weakly sensitive to the aerosol model assumptions throughout the day, with biases lower than 6 % on the COT and 3 % on the CER. The stability of the retrieval over time is analysed. For observations outside of the backscattering glory region, the time series of the aerosol and cloud properties are physically consistent, which confirms the ability of the retrieval to monitor the temporal evolution of aerosol above-cloud events over the SEAO.Research Council of NorwayNetB

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

The development of a theory-based intervention to promote appropriate disclosure of a diagnosis of dementia

Background: The development and description of interventions to change professional practice are often limited by the lack of an explicit theoretical and empirical basis. We set out to develop an intervention to promote appropriate disclosure of a diagnosis of dementia based on theoretical and empirical work. Methods: We identified three key disclosure behaviours: finding out what the patient already knows or suspects about their diagnosis; using the actual words 'dementia' or 'Alzheimer's disease' when talking to the patient; and exploring what the diagnosis means to the patient. We conducted a questionnaire survey of older peoples' mental health teams (MHTs) based upon theoretical constructs from the Theory of Planned Behaviour (TPB) and Social Cognitive Theory (SCT) and used the findings to identify factors that predicted mental health professionals' intentions to perform each behaviour. We selected behaviour change techniques likely to alter these factors. Results: The change techniques selected were: persuasive communication to target subjective norm; behavioural modelling and graded tasks to target self-efficacy; persuasive communication to target attitude towards the use of explicit terminology when talking to the patient; and behavioural modelling by MHTs to target perceived behavioural control for finding out what the patient already knows or suspects and exploring what the diagnosis means to the patient. We operationalised these behaviour change techniques using an interactive 'pen and paper' intervention designed to increase intentions to perform the three target behaviours. Conclusion : It is feasible to develop an intervention to change professional behaviour based upon theoretical models, empirical data and evidence based behaviour change techniques. The next step is to evaluate the effect of such an intervention on behavioural intention. We argue that this approach to development and reporting of interventions will contribute to the science of implementation by providing replicable interventions that illuminate the principles and processes underlying change.This project is funded by UK Medical Research Council, Grant reference number G0300999. Jeremy Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake. Jill Francis is funded by the Chief Scientist Office of the Scottish Government Health Directorate. The views expressed in this study are those of the authors

The influence of groundwater abstraction on interpreting climate controls and extreme recharge events from well hydrographs in semi-arid South Africa

There is a scarcity of long-term groundwater hydrographs from sub-Saharan Africa to investigate groundwater sustainability, processes and controls. This paper presents an analysis of 21 hydrographs from semi-arid South Africa. Hydrographs from 1980 to 2000 were converted to standardised groundwater level indices and rationalised into four types (C1–C4) using hierarchical cluster analysis. Mean hydrographs for each type were cross-correlated with standardised precipitation and streamflow indices. Relationships with the El Niño–Southern Oscillation (ENSO) were also investigated. The four hydrograph types show a transition of autocorrelation over increasing timescales and increasingly subdued responses to rainfall. Type C1 strongly relates to rainfall, responding in most years, whereas C4 notably responds to only a single extreme event in 2000 and has limited relationship with rainfall. Types C2, C3 and C4 have stronger statistical relationships with standardised streamflow than standardised rainfall. C3 and C4 changes are significantly (p < 0.05) correlated to the mean wet season ENSO anomaly, indicating a tendency for substantial or minimal recharge to occur during extreme negative and positive ENSO years, respectively. The range of different hydrograph types, sometimes within only a few kilometres of each other, appears to be a result of abstraction interference and cannot be confidently attributed to variations in climate or hydrogeological setting. It is possible that high groundwater abstraction near C3/C4 sites masks frequent small-scale recharge events observed at C1/C2 sites, resulting in extreme events associated with negative ENSO years being more visible in the time series

Developing the content of two behavioural interventions : using theory-based interventions to promote GP management of upper respiratory tract infection without prescribing antibiotics #1

Background: Evidence shows that antibiotics have limited effectiveness in the management of upper respiratory tract infection (URTI) yet GPs continue to prescribe antibiotics. Implementation research does not currently provide a strong evidence base to guide the choice of interventions to promote the uptake of such evidence-based practice by health professionals. While systematic reviews demonstrate that interventions to change clinical practice can be effective, heterogeneity between studies hinders generalisation to routine practice. Psychological models of behaviour change that have been used successfully to predict variation in behaviour in the general population can also predict the clinical behaviour of healthcare professionals. The purpose of this study was to design two theoretically-based interventions to promote the management of upper respiratory tract infection (URTI) without prescribing antibiotics. Method: Interventions were developed using a systematic, empirically informed approach in which we: selected theoretical frameworks; identified modifiable behavioural antecedents that predicted GPs intended and actual management of URTI; mapped these target antecedents on to evidence-based behaviour change techniques; and operationalised intervention components in a format suitable for delivery by postal questionnaire. Results: We identified two psychological constructs that predicted GP management of URTI: "Self-efficacy," representing belief in one's capabilities, and "Anticipated consequences," representing beliefs about the consequences of one's actions. Behavioural techniques known to be effective in changing these beliefs were used in the design of two paper-based, interactive interventions. Intervention 1 targeted self-efficacy and required GPs to consider progressively more difficult situations in a "graded task" and to develop an "action plan" of what to do when next presented with one of these situations. Intervention 2 targeted anticipated consequences and required GPs to respond to a "persuasive communication" containing a series of pictures representing the consequences of managing URTI with and without antibiotics. Conclusion: It is feasible to systematically develop theoretically-based interventions to change professional practice. Two interventions were designed that differentially target generalisable constructs predictive of GP management of URTI. Our detailed and scientific rationale for the choice and design of our interventions will provide a basis for understanding any effects identified in their evaluation. Trial registration: Clinicaltrials.gov NCT00376142This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

Anomalous tqγtq\gamma coupling effects in exclusive radiative B-meson decays

The top-quark FCNC processes will be searched for at the CERN LHC, which are correlated with the B-meson decays. In this paper, we study the effects of top-quark anomalous interactions $tq\gamma$ in the exclusive radiative $B\to K^*\gamma$ and $B\to\rho\gamma$ decays. With the current experimental data of the branching ratios, the direct CP and the isospin asymmetries, bounds on the coupling $\kappa_{tcR}^{\gamma}$ from $B\to K^*\gamma$ and $\kappa_{tuR}^{\gamma}$ from $B\to \rho\gamma$ decays are derived, respectively. The bound on $|\kappa_{tcR}^{\gamma}|$ from ${\mathcal B}(B\to K^{*}\gamma)$ is generally compatible with that from ${\mathcal B}(B\to X_{s}\gamma)$. However, the isospin asymmetry $\Delta(K^{*}\gamma)$ further restrict the phase of $\kappa_{tcR}^{\gamma}$, and the combined bound results in the upper limit, $\mathcal B(t\to c\gamma)<0.21$, which is lower than the CDF result. For real $\kappa_{tcR}^{\gamma}$, the upper bound on $\mathcal B(t\to c\gamma)$ is about of the same order as the $5\sigma$ discovery potential of ATLAS with an integrated luminosity of $10 {\rm fb}^{-1}$. For $B\to\rho\gamma$ decays, the NP contribution is enhanced by a large CKM factor $|V_{ud}/V_{td}|$, and the constraint on $tu\gamma$ coupling is rather restrictive, $\mathcal B(t\to u\gamma)<1.44\times 10^{-5}$. With refined measurements to be available at the LHCb and the future super-B factories, we can get close correlations between $B\to V \gamma$ and the rare $t\to q\gamma$ decays, which will be studied directly at the LHC ATLAS and CMS.Comment: 25 pages, 15 figures, pdflate

Adiponectin levels in people with Latent Autoimmune Diabetes-a case control study

<p>Abstract</p> <p>Background</p> <p>To examine adiponectin levels in people with Latent Autoimmune Diabetes in Adults using a matched pair case control study.</p> <p>Findings</p> <p>Patients with LADA (n = 64), were matched for sex with type 2 diabetic and non-diabetic controls. A matched paired T-test was used to examine average adiponectin levels in the LADA patients' versus controls. The average adiponectin level for the LADA patients was 9.96 μg/ml compared to 6.4 μg/ml for Type 2 matched controls and 9.6 μg/ml for non-diabetic controls. Mean difference for the LADA-type 2 comparison was calculated after data was log transformed and showed a difference of 1.58 μg/ml (95%CI: 1.28-1.95, p = 0.0001). There was no significant difference between LADA and non-diabetic controls (p = 0.54).</p> <p>Conclusions</p> <p>Adiponectin levels are higher among people with LADA compared to those with type 2 diabetes and are equivalent to levels seen in non-diabetic controls. This suggests that risk of complications in LADA, as with type 1 diabetes may be related more to glycaemic control rather than to factors of the metabolic syndrome.</p

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

Identification of undiagnosed atrial fibrillation patients using a machine learning risk prediction algorithm and diagnostic testing (PULsE-AI): Study protocol for a randomised controlled trial.

Atrial fibrillation (AF) is associated with an increased risk of stroke, enhanced stroke severity, and other comorbidities. However, AF is often asymptomatic, and frequently remains undiagnosed until complications occur. Current screening approaches for AF lack either cost-effectiveness or diagnostic sensitivity; thus, there is interest in tools that could be used for population screening. An AF risk prediction algorithm, developed using machine learning from a UK dataset of 2,994,837 patients, was found to be more effective than existing models at identifying patients at risk of AF. Therefore, the aim of the trial is to assess the effectiveness of this risk prediction algorithm combined with diagnostic testing for the identification of AF in a real-world primary care setting. Eligible participants (aged ≥30 years and without an existing AF diagnosis) registered at participating UK general practices will be randomised into intervention and control arms. Intervention arm participants identified at highest risk of developing AF (algorithm risk score ≥ 7.4%) will be invited for a 12‑lead electrocardiogram (ECG) followed by two-weeks of home-based ECG monitoring with a KardiaMobile device. Control arm participants will be used for comparison and will be managed routinely. The primary outcome is the number of AF diagnoses in the intervention arm compared with the control arm during the research window. If the trial is successful, there is potential for the risk prediction algorithm to be implemented throughout primary care for narrowing the population considered at highest risk for AF who could benefit from more intensive screening for AF. Trial Registration: NCT04045639