The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Facial expressions depicting compassionate and critical emotions: the development and validation of a new emotional face stimulus set

Attachment with altruistic others requires the ability to appropriately process affiliative and kind facial cues. Yet there is no stimulus set available to investigate such processes. Here, we developed a stimulus set depicting compassionate and critical facial expressions, and validated its effectiveness using well-established visual-probe methodology. In Study 1, 62 participants rated photographs of actors displaying compassionate/kind and critical faces on strength of emotion type. This produced a new stimulus set based on N = 31 actors, whose facial expressions were reliably distinguished as compassionate, critical and neutral. In Study 2, 70 participants completed a visual-probe task measuring attentional orientation to critical and compassionate/kind faces. This revealed that participants lower in self-criticism demonstrated enhanced attention to compassionate/kind faces whereas those higher in self-criticism showed no bias. To sum, the new stimulus set produced interpretable findings using visual-probe methodology and is the first to include higher order, complex positive affect displays

Interplay between manganese and iron in pneumococcal pathogenesis: role of the orphan response regulator RitR

Streptococcus pneumoniae (the pneumococcus) is a major human pathogen that is carried asymptomatically in the nasopharynx by up to 70% of the human population. Translocation of the bacteria into internal sites can cause a range of diseases, such as pneumonia, otitis media, meningitis, and bacteremia. This transition from nasopharynx to growth at systemic sites means that the pneumococcus needs to adjust to a variety of environmental conditions, including transition metal ion availability. Although it is an important nutrient, iron potentiates oxidative stress, and it is established that in S. pneumoniae, expression of iron transport systems and proteins that protect against oxidative stress are regulated by an orphan response regulator, RitR. In this study, we investigated the effect of iron and manganese ion availability on the growth of a ritR mutant. Deletion of ritR led to impaired growth of bacteria in high-iron medium, but this phenotype could be suppressed with the addition of manganese. Measurement of metal ion accumulation indicated that manganese prevents iron accumulation. Furthermore, the addition of manganese also led to a reduction in the amount of hydrogen peroxide produced by bacterial cells. Studies of virulence in a murine model of infection indicated that RitR was not essential for pneumococcal survival and suggested that derepression of iron uptake systems may enhance the survival of pneumococci in some niches

Genetic parameters for faecal egg count, packed-cell volume and body-weight in Santa Inês lambs

Worm infection is one of the main factors responsible for economic losses in sheep breeding in Brazil. Random regression analysis was used to estimate genetic parameters for the factors faecal egg-count (FEC), packed-cell volume (PCV) and body weight (BW) in Santa Inês lambs. Data from 119 female, offspring of nine rams, were collected between December, 2005 and December, 2006, from the experimental flock of Embrapa Tabuleiros Costeiros, the Brazilian Agricultural Research Corporation located in Frei Paulo, SE, Brazil. After weaning, females were drenched until the faecal egg count had dropped to zero. Two natural challenges were undertaken. FEC heritability was extremely variable, this increasing from 0.04 to 0.27 in the first challenge and from 0.01 to 0.52 during the second. PCV heritability peaks were 0.31 and 0.12 in the first and second challenges, respectively. In the second challenge, BW heritability was close to 0.90. The genetic correlations among these traits did not differ from zero. There is the possibility of increasing parasite resistance in Santa Inês by selecting those animals with lower FEC. Selection to increase resistance will not adversely affect lamb-growth, although lambs with a slow growth-rate may be more susceptible to infection

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

Phenotype Fingerprinting Suggests the Involvement of Single-Genotype Consortia in Degradation of Aromatic Compounds by Rhodopseudomonas palustris

Anaerobic degradation of complex organic compounds by microorganisms is crucial for development of innovative biotechnologies for bioethanol production and for efficient degradation of environmental pollutants. In natural environments, the degradation is usually accomplished by syntrophic consortia comprised of different bacterial species. This strategy allows consortium organisms to reduce efforts required for maintenance of the redox homeostasis at each syntrophic level. Cellular mechanisms that maintain the redox homeostasis during the degradation of aromatic compounds by one organism are not fully understood. Here we present a hypothesis that the metabolically versatile phototrophic bacterium Rhodopseudomonas palustris forms its own syntrophic consortia, when it grows anaerobically on p-coumarate or benzoate as a sole carbon source. We have revealed the consortia from large-scale measurements of mRNA and protein expressions under p-coumarate, benzoate and succinate degrading conditions using a novel computational approach referred as phenotype fingerprinting. In this approach, marker genes for known R. palustris phenotypes are employed to determine the relative expression levels of genes and proteins in aromatics versus non-aromatics degrading condition. Subpopulations of the consortia are inferred from the expression of phenotypes and known metabolic modes of the R. palustris growth. We find that p-coumarate degrading conditions may lead to at least three R. palustris subpopulations utilizing p-coumarate, benzoate, and CO2 and H2. Benzoate degrading conditions may also produce at least three subpopulations utilizing benzoate, CO2 and H2, and N2 and formate. Communication among syntrophs and inter-syntrophic dynamics in each consortium are indicated by up-regulation of transporters and genes involved in the curli formation and chemotaxis. The N2-fixing subpopulation in the benzoate degrading consortium has preferential activation of the vanadium nitrogenase over the molybdenum nitrogenase. This subpopulation in the consortium was confirmed in an independent experiment by consumption of dissolved nitrogen gas under the benzoate degrading conditions

Cardiovascular risk assessment scores for people with diabetes: a systematic review

People with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Multivariate cardiovascular risk scores have been used in many countries to identify individuals who are at high risk of CVD. These risk scores include those originally developed in individuals with diabetes and those developed in a general population. This article reviews the published evidence for the performance of CVD risk scores in diabetic patients by: (1) examining the overall rationale for using risk scores; (2) systematically reviewing the literature on available scores; and (3) exploring methodological issues surrounding the development, validation and comparison of risk scores. The predictive performance of cardiovascular risk scores varies substantially between different populations. There is little evidence to suggest that risk scores developed in individuals with diabetes estimate cardiovascular risk more accurately than those developed in the general population. The inconsistency in the methods used in evaluation studies makes it difficult to compare and summarise the predictive ability of risk scores. Overall, CVD risk scores rank individuals reasonably accurately and are therefore useful in the management of diabetes with regard to targeting therapy to patients at highest risk. However, due to the uncertainty in estimation of true risk, care is needed when using scores to communicate absolute CVD risk to individuals

Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection

The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (∼1.3% of all genes) in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans–based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens