Verified and potential pathogens of predatory mites (Acari: Phytoseiidae)

Several species of phytoseiid mites (Acari: Phytoseiidae), including species of the genera Amblyseius, Galendromus, Metaseiulus, Neoseiulus, Phytoseiulus and Typhlodromus, are currently reared for biological control of various crop pests and/or as model organisms for the study of predator¿prey interactions. Pathogen-free phytoseiid mites are important to obtain high efficacy in biological pest control and to get reliable data in mite research, as pathogens may affect the performance of their host or alter their reproduction and behaviour. Potential and verified pathogens have been reported for phytoseiid mites during the past 25 years. The present review provides an overview, including potential pathogens with unknown host effects (17 reports), endosymbiotic Wolbachia (seven reports), other bacteria (including Cardinium and Spiroplasma) (four reports), cases of unidentified diseases (three reports) and cases of verified pathogens (six reports). From the latter group four reports refer to Microsporidia, one to a fungus and one to a bacterium. Only five entities have been studied in detail, including Wolbachia infecting seven predatory mite species, other endosymbiotic bacteria infecting Metaseiulus (Galendromus, Typhlodromus) occidentalis (Nesbitt), the bacterium Acaricomes phytoseiuli infecting Phytoseiulus persimilis Athias-Henriot, the microsporidium Microsporidium phytoseiuli infecting P. persimilis and the microsporidium Oligosproridium occidentalis infecting M. occidentalis. In four cases (Wolbachia, A. phytoseiuli, M. phytoseiuli and O. occidentalis) an infection may be connected with fitness costs of the host. Moreover, infection is not always readily visible as no obvious gross symptoms are present. Monitoring of these entities on a routine and continuous basis should therefore get more attention, especially in commercial mass-production. Special attention should be paid to field-collected mites before introduction into the laboratory or mass rearing, and to mites that are exchanged among rearing facilities. However, at present general pathogen monitoring is not yet practical as effects of many entities are unknown. More research effort is needed concerning verified and potential pathogens of commercially reared arthropods and those used as model organisms in research

Physicians perceived usefulness of high-cost diagnostic imaging studies: results of a referral study in a German medical quality network

BACKGROUND: Medical and technological progress has led to increased numbers of diagnostic tests, some of them inducing high financial costs. In Germany, high-cost diagnostic imaging is performed by a medical specialist after referral by a general practitioner (GP) or specialist in primary care. The aim of this study was to evaluate the physicians' perceived usefulness of high-cost diagnostic imaging in patients with different clinical conditions. METHODS: Thirty-four GPs, one neurologist and one orthopaedic specialist in ambulatory care from a Medical Quality Network documented 234 referrals concerning 97 MRIs, 96 CTs-scan and 41 intracardiac catheters in a three month period. After having received the test results, they indicated if these were useful for diagnosis and treatment of the patient. RESULTS: The physicians' perceived usefulness of tests was lowest in suspected cerebral disease (40% of test results were seen as useful), cervical spine problems (64%) and unexplained abdominal complaints (67%). The perceived usefulness was highest in musculoskeletal symptoms (94%) and second best in cardiological diseases (82%). CONCLUSION: The perceived usefulness of high-cost diagnostic imaging was lower in unexplained complaints than in specific diseases. Interventions to improve the effectiveness and efficiency of test ordering should focus on clinical decision making in conditions where GPs perceived low usefulness

Geographical inequalities in lung cancer management and survival in South East England: evidence of variation in access to oncology services?

This study aimed to determine whether the management and survival of patients with lung cancer varied among 26 health authorities in South East England. The Thames Cancer Registry identified patients diagnosed with lung cancer (ICD-10 codes C33-C34) between 1995 and 1999. After excluding death certificate only patients, 32,818 (81%) patients were analysed. The proportions of patients receiving active treatment varied among health authorities between 5 and 17% for non-investigative surgery, 4 and 17% for any chemotherapy, 8 and 30% for any radiotherapy and 15 and 42% for any active treatment. One-year patient survival ranged from 11 to 34%. There was evidence of health authority level variation even after adjusting for case mix. Patients whose first hospital attendance was at a radiotherapy centre were more likely to receive active treatment (OR 1.72, 95% CI 1.21-2.46), chemotherapy (1.38, 1.06-1.79) or radiotherapy (1.86, 1.28-2.71). There was some evidence that patients whose first hospital attendance was at a radiotherapy centre survived longer. This study shows there is geographical inequality in the treatment given to lung cancer patients and patient survival in South East England. There was some evidence to suggest that these inequalities might be explained by variations in access to oncology services. Future studies should investigate the pathways and barriers to specialist care in this condition

The cystic fibrosis transmembrane recruiter the alter ego of CFTR as a multi-kinase anchor

This review focuses on a newly discovered interaction between protein kinases involved in cellular energetics, a process that may be disturbed in cystic fibrosis for unknown reasons. I propose a new model where kinase-mediated cellular transmission of energy provides mechanistic insight to a latent role of the cystic fibrosis transmembrane conductance regulator (CFTR). I suggest that CFTR acts as a multi-kinase recruiter to the apical epithelial membrane. My group finds that, in the cytosol, two protein kinases involved in cell energy homeostasis, nucleoside diphosphate kinase (NDPK) and AMP-activated kinase (AMPK), bind one another. Preliminary data suggest that both can also bind CFTR (function unclear). The disrupted role of this CFTR-kinase complex as ‘membrane transmitter to the cell’ is proposed as an alternative paradigm to the conventional ion transport mediated and CFTR/chloride-centric view of cystic fibrosis pathogenesis. Chloride remains important, but instead, chloride-induced control of the phosphohistidine content of one kinase component (NDPK, via a multi-kinase complex that also includes a third kinase, CK2; formerly casein kinase 2). I suggest that this complex provides the necessary near-equilibrium conditions needed for efficient transmission of phosphate energy to proteins controlling cellular energetics. Crucially, a new role for CFTR as a kinase controller is proposed with ionic concentration acting as a signal. The model posits a regulatory control relay for energy sensing involving a cascade of protein kinases bound to CFTR

The Selectivity of Milking of Dunaliella salina

The process of the simultaneous production and extraction of carotenoids, milking, of Dunaliella salina was studied. We would like to know the selectivity of this process. Could all the carotenoids produced be extracted? And would it be possible to vary the profile of the produced carotenoids and, consequently, influence the type of carotenoids extracted? By using three different D. salina strains and three different stress conditions, we varied the profiles of the carotenoids produced. Between Dunaliella bardawil and D. salina 19/18, no remarkable differences were seen in the extraction profiles, although D. salina 19/18 seemed to be better extractable. D. salina 19/25 was not “milkable” at all. The milking process could only be called selective for secondary carotenoids in case gentle mixing was used. In aerated flat-panel photobioreactors, extraction was much better, but selectiveness decreased and also chlorophyll and primary carotenoids were extracted. This was possibly related to cell damage due to shear stress

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Assessment of post-competition peak blood lactate in male and female master swimmers aged 40–79 years and its relationship with swimming performance

The main purpose of this study was to measure the postcompetition blood lactate concentration ([La]b) in master swimmers of both sexes aged between 40 and 79 years in order to relate it to age and swimming performance. One hundred and eight swimmers participating in the World Master Championships were assessed for [La]b and the average rate of lactate accumulation (La’;mmol l-1 s-1) was calculated. In addition, 77 of them were also tested for anthropometric measures. When the subjects were divided into 10-year age groups, males exhibited higher [La]b than women (factorial ANOVA, P < 0.01) and a steeper decline with ageing than female subjects. Overall, mean values (SD) of [La]b were 10.8 (2.8), 10.3 (2.0), 10.3 (1.9), 8.9 (3.2) mmol l-1 in women, and 14.2 (2.5), 12.4 (2.5), 11.0 (1.6), 8.2 (2.0) mmol l-1 in men for, respectively, 40–49, 50–59, 60–69, 70–79 years’ age groups. When, however, [La]b values were normalised for a ‘‘speed index’’, which takes into account swimming speed as a percentage of world record, these sex-related differences, although still present, were considerably attenuated. Furthermore, the differences in La’ between males and females were larger in the 40–49 age group (0.34 vs 0.20 mmol l-1 s-1 for 50-m distance) than in the 70–79 age group (0.12 vs 0.14 mmol l-1 s-1 for 50-m distance). Different physiological factors, supported by the considered anthropometric measurements, are suggested to explain the results

Anti-EGFR Antibody Efficiently and Specifically Inhibits Human TSC2−/− Smooth Muscle Cell Proliferation. Possible Treatment Options for TSC and LAM

BACKGROUND: Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2(-/-) ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, do not produce the TSC2 gene product, tuberin. TSC2(-/-) ASM cell proliferation is EGF-dependent. METHODS AND FINDINGS: Effects of EGF on proliferation of TSC2(-/-) ASM cells and TSC2(-/-) ASM cells transfected with TSC2 gene were determined. In contrast to TSC2(-/-) ASM cells, growth of TSC2-transfected cells was not dependent on EGF. Moreover, phosphorylation of Akt, PTEN, Erk and S6 was significantly decreased. EGF is a proliferative factor of TSC2(-/-) ASM cells. Exposure of TSC2(-/-) ASM cells to anti-EGFR antibodies significantly inhibited their proliferation, reverted reactivity to HMB45 antibody, a marker of TSC2(-/-) cell phenotype, and inhibited constitutive phosphorylation of S6 and ERK. Exposure of TSC2(-/-) ASM cells to rapamycin reduced the proliferation rate, but only when added at plating time. Although rapamycin efficiently inhibited S6 phosphorylation, it was less efficient than anti-EGFR antibody in reverting HMB45 reactivity and blocking ERK phosphorylation. In TSC2(-/-) ASM cells specific PI3K inhibitors (e.g. LY294002, wortmannin) and Akt1 siRNA had little effect on S6 and ERK phosphorylation. Following TSC2-gene transfection, Akt inhibitor sensitivity was observed. CONCLUSION: Our results show that an EGF independent pathway is more important than that involving IGF-I for growth and survival of TSC(-/-) ASM cells, and such EGF-dependency is the result of the lack of tuberin

The impact of atmosphere–ocean–wave coupling on the near-surface wind speed in forecasts of extratropical cyclones

Accurate modelling of air–sea surface exchanges is crucial for reliable extreme surface windspeed forecasts. While atmosphere-only weather forecast models represent ocean and wave effects through sea-state independent parametrizations, coupled multi-model systems capture sea-state dynamics by integrating feedbacks between the atmosphere, ocean and wave model components. Here, we investigate the sensitivity of extreme surface wind speeds to air–sea exchanges at the kilometre scale using coupled and uncoupled configurations of the Met Office’s UK Regional Coupled Environmental Prediction system. The case period includes the passage of extra-tropical cyclones Helen, Ali, and Bronagh, which brought maximum gusts of 36 ms−1 over the UK. Compared with the atmosphere-only results, coupling to the ocean decreases the domain-average sea-surface temperature by up to 0.5 K. Inclusion of coupling to waves reduce the 98th percentile 10-m wind speed by up to 2 ms−1 as young, growing wind waves reduce the wind speed by increasing the sea-surface aerodynamic roughness. Impacts on gusts are more modest, with local reductions of up to 1 ms−1, due to enhanced boundary-layer turbulence which partially offsets air–sea momentum transfer. Using a new drag parametrization based on the Coupled Ocean–Atmosphere Response Experiment 4.0 parametrization, with a cap on the neutral drag coefficient and reduction for wind speeds exceeding 27 ms−1, the atmosphere-only model achieves equivalent impacts on 10-m wind speeds and gusts as from coupling to waves. Overall, the new drag parametrization achieves the same 20% improvement in forecast 10-m wind-speed skill as coupling to waves, with the advantage of saving the computational cost of the ocean and wave models

Differential effects of cytokines and corticosteroids on Toll-like receptor 2 expression and activity in human airway epithelia

<p>Abstract</p> <p>Background</p> <p>The recognition of microbial molecular patterns via Toll-like receptors (TLRs) is critical for mucosal defenses.</p> <p>Methods</p> <p>Using well-differentiated primary cultures of human airway epithelia, we investigated the effects of exposure of the cells to cytokines (TNF-α and IFN-γ) and dexamethasone (dex) on responsiveness to the TLR2/TLR1 ligand Pam3CSK4. Production of IL-8, CCL20, and airway surface liquid antimicrobial activity were used as endpoints.</p> <p>Results</p> <p>Microarray expression profiling in human airway epithelia revealed that first response cytokines markedly induced TLR2 expression. Real-time PCR confirmed that cytokines (TNF-α and IFN-γ), dexamethasone (dex), or cytokines + dex increased TLR2 mRNA abundance. A synergistic increase was seen with cytokines + dex. To assess TLR2 function, epithelia pre-treated with cytokines ± dex were exposed to the TLR2/TLR1 ligand Pam3CSK4 for 24 hours. While cells pre-treated with cytokines alone exhibited significantly enhanced IL-8 and CCL20 secretion following Pam3CSK4, mean IL-8 and CCL20 release decreased in Pam3CSK4 stimulated cells following cytokines + dex pre-treatment. This marked increase in inflammatory gene expression seen after treatment with cytokines followed by the TLR2 ligand did not correlate well with NF-κB, Stat1, or p38 MAP kinase pathway activation. Cytokines also enhanced TLR2 agonist-induced beta-defensin 2 mRNA expression and increased the antimicrobial activity of airway surface liquid. Dex blocked these effects.</p> <p>Conclusion</p> <p>While dex treatment enhanced TLR2 expression, co-administration of dex with cytokines inhibited airway epithelial cell responsiveness to TLR2/TLR1 ligand over cytokines alone. Enhanced functional TLR2 expression following exposure to TNF-α and IFN-γ may serve as a dynamic means to amplify epithelial innate immune responses during infectious or inflammatory pulmonary diseases.</p