Phosphoinositide 3-kinase: a critical signalling event in pulmonary cells

Phosphoinositide 3-kinases (PI-3Ks) are enzymes that generate lipid second messenger molecules, resulting in the activation of multiple intracellular signalling cascades. These events regulate a broad array of cellular responses including survival, activation, differentiation and proliferation and are now recognised to have a key role in a number of physiological and pathophysiological processes in the lung. PI-3Ks contribute to the pathogenesis of asthma by influencing the proliferation of airways smooth muscle and the recruitment of eosinophils, and affect the balance between the harmful and protective responses in pulmonary inflammation and infection by the modulation of granulocyte recruitment, activation and apoptosis. In addition they also seem to exert a critical influence on the malignant phenotype of small cell lung cancer. PI-3K isoforms and their downstream targets thus provide novel therapeutic targets for intervention in a broad spectrum of respiratory diseases

Fungi in the Marine Environment: Open Questions and Unsolved Problems.

Terrestrial fungi play critical roles in nutrient cycling and food webs and can shape macroorganism communities as parasites and mutualists. Although estimates for the number of fungal species on the planet range from 1.5 to over 5 million, likely fewer than 10% of fungi have been identified so far. To date, a relatively small percentage of described species are associated with marine environments, with ∼1,100 species retrieved exclusively from the marine environment. Nevertheless, fungi have been found in nearly every marine habitat explored, from the surface of the ocean to kilometers below ocean sediments. Fungi are hypothesized to contribute to phytoplankton population cycles and the biological carbon pump and are active in the chemistry of marine sediments. Many fungi have been identified as commensals or pathogens of marine animals (e.g., corals and sponges), plants, and algae. Despite their varied roles, remarkably little is known about the diversity of this major branch of eukaryotic life in marine ecosystems or their ecological functions. This perspective emerges from a Marine Fungi Workshop held in May 2018 at the Marine Biological Laboratory in Woods Hole, MA. We present the state of knowledge as well as the multitude of open questions regarding the diversity and function of fungi in the marine biosphere and geochemical cycles

Comparison of Eight Methods for the Extraction of Bacillus atrophaeus Spore DNA from Eleven Common Interferents and a Common Swab

Eight DNA extraction products or methods (Applied Biosystems PrepFiler Forensic DNA Extraction Kit; Bio-Rad Instagene Only, Bio-Rad Instagene & Spin Column Purification; EpiCentre MasterPure DNA & RNA Kit; FujiFilm QuickGene Mini80; Idaho Technologies 1-2-3 Q-Flow Kit; MoBio UltraClean Microbial DNA Isolation Kit; Sigma Extract-N-Amp Plant and Seed Kit) were adapted to facilitate extraction of DNA under BSL3 containment conditions. DNA was extracted from 12 common interferents or sample types, spiked with spores of Bacillus atropheaus. Resulting extracts were tested by real-time PCR. No one method was the best, in terms of DNA extraction, across all sample types. Statistical analysis indicated that the PrepFiler method was the best method from six dry powders (baking, biological washing, milk, plain flour, filler and talcum) and one solid (Underarm deodorant), the UltraClean method was the best from four liquids (aftershave, cola, nutrient broth, vinegar), and the MasterPure method was the best from the swab sample type. The best overall method, in terms of DNA extraction, across all sample types evaluated was the UltraClean method

Validation of activity questionnaires in patients with cystic fibrosis by accelerometry and cycle ergometry

BACKGROUND: The objective of this study was to validate physical activity questionnaires for cystic fibrosis (CF) against accelerometry and cycle ergometry. METHODS: 41 patients with CF (12-42 years) completed the Habitual Activity Estimation Scale (HAES), the 7-Day Physical Activity Recall questionnaire (7D-PAR) and the Lipid Research Clinics questionnaire (LRC) and performed an incremental exercise test according to the Godfrey protocol up to volitional fatigue. Time spent in moderate and vigorous physical activity (MVPA) assessed objectively by accelerometry was related to the time spent in the respective activity categories by correlation analyses and calculating intraclass correlation coefficients (ICC). Furthermore, the results of the exercise test were correlated with the results of the questionnaires. RESULTS: Time spent in the categories 'hard','very hard' and 'hard & very hard' of the 7D-PAR (0.41 > r > 0.56) and 'active' (r = 0.33) of the HAES correlated significantly with MVPA. The activity levels of the LRC were not related to objectively determined physical activity. Significant ICCs were only observed between the 7D-PAR activitiy categories and MVPA (ICC = 0.40-0.44). Only the LRC showed moderate correlations with the exercise test (Wmax: r = 0.46, p = 0.002; VO2peak: r = 0.32, p = 0.041). CONCLUSIONS: In conclusion, the activity categories 'hard' and 'very hard' of the 7D-PAR best reflected objectively measured MVPA. Since the association was at most moderate, the 7D-PAR may be selected to describe physical activity within a population. None of the evaluated questionnaires was able to generate valid physical activity data exercise performance data at the individual level. Neither did any of the questionnaires provide a valid assessment of aerobic fitness on an invidual leve

Childhood abdominal pain in primary care: design and patient selection of the HONEUR abdominal pain cohort

Background: Abdominal pain in children is a common complaint presented to the GP. However, the prognosis and prognostic factors of childhood abdominal pain are almost exclusively studied in referred children. This cohort study aims at describing prognosis and prognostic factors of childhood abdominal pain in primary care. In this paper we describe methods used for data-collection and determine possible selective recruitment. Methods/Design: We conducted an observational, prospective cohort study with a 1-year follow-up. From May 2004 to March 2006, 53 Dutch GPs recruited consecutive children aged 4-17 years with a new episode of abdominal pain not preceded by a consultation for this complaint in the previous 3 months. Participants filled in standardized questionnaires, and faeces and urine were sampled. To evaluate selective recruitment, the electronic medical records of participating GPs were retrospectively searched for eligible non-included children. Discussion: This study allows us to describe prognosis and prognostic factors of childhood abdominal pain in primary care. A total of 305 children were included of whom 142 (46.6%) met predefined criteria for chronic/recurrent abdominal pain at presentation; from the total group of eligible children identified from the electronic medical record, 27% were included. The included children were significantly younger than non-included children (mean age 8.49 and 9.20 years). In proportion to identified eligible children, significantly less children diagnosed with "gastroenteritis" (6.8%) and significantly more children with "generalized abdominal pain" (39%) were included compared to the 27% that was expected. This cohort represents young school-aged children consulting GPs for a new episode of abdominal pain, not diagnosed as gastroenteritis. Almost half of them fulfil the criteria for chronic abdominal pain at presentation

Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy

Leprosy affects skin and peripheral nerves. Although we have antibiotics to treat the mycobacterial infection, the accompanying inflammation is a major part of the disease process. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called reactions. These are associated with worsening of nerve damage. However, diagnosing these reactions is not straightforward. They can be diagnosed clinically by examination or by microscopic examination of the skin biopsies. We studied a cohort of 303 newly diagnosed leprosy patients in India and compared the diagnosis rates by clinical examination and microscopy and found that the microscopic diagnosis has higher rates of diagnosis for both types of reaction. This suggests that clinicians and pathologists have different thresholds for diagnosing reactions. More work is needed to optimise both clinical and pathological diagnosis. In this cohort 43% of patients had Borderline Tuberculoid leprosy, an immunologically active type, and 20% of the biopsies showed only minimal inflammation, perhaps these patients had very early disease or self-healing. The public health implication of this work is that leprosy centres need to be supported by pathologists to help with the clinical management of difficult cases

The influence of online resources on student–lecturer relationship in higher education: a comparison study

The internet has become a key resource for students’ higher education studies due to both its availability and currency. Previously within higher education, lectures, books and course materials were the only sources of information. This change, to more open access to information and more online materials being accessed outside of those provided by lecturers, and indeed institutions, is likely to accelerate and change the way students are learning. This study aims to help institutions understand better the impact of these changes on the student–lecturer relationship by exploring students’ perceptions of their studies in terms of power and students’ academic engagement in the classroom. The importance of the internet (online learning resources) to students’ achievements, the importance of lecturers and the student–lecturer relationship have all been widely investigated. However, limited research has been undertaken examining the impact of students’ use of the internet on the student–lecturer relationship, or comparing this across different countries and cultures. To address this, data were collected via semi- structured questionnaires distributed to undergraduate students from three countries: United Kingdom, Saudi Arabia and Kenya. Quantitative data were analysed using a simple statistical analysis approach and qualitative data were analysed using a thematic analysis approach. The results showed that students’ use of the internet has improved students’ academic self-confidence, academic self-reliance and student– lecturer connectedness, but students’ use of the internet has increased the gap in the student–lecturer expert relationship and referent relationship. The impact and rea- sons for this differed between the countries involved in this study

Distribution of sulfur in power supply lignite from North Hungary

Abstract The present article discusses the results of measurements carried out to assess the distribution of different sulfur types in lignite samples deriving from two opencast lignite mines near the villages of Bükkábrány and Visonta. These mines ensure the continuous supply of fuel for one of Hungary's largest thermal power plant. According to our findings no significant differences could be identified between the samples of the two mines based on their total sulfur (St) content. Both lignite types were classified as coals with medium-sulfur content according to the system of Chou (1990). A majority of total sulfur is accumulated in lignite, while in the intercalated carbonaceous shale total sulfur is present in minor amounts. Usually the sequence of the distribution of sulfur among the different bond forms in lignite collected from opencast mine of Visonta is as follows: pyritic sulfur (Sp) > organic sulfur (Sorg) > sulfate sulfur (SSOorg4). In the samples collected from Visonta and Bükkábrány quantities of total sulfur were similar. However, some difference in their distribution among various sulfur types were noted. Although half of the samples were weathered and the amount of pyrite sulfur must have been higher in the weathered lignite of Bükkábrány preceding the oxidation process, the sequence of the distribution of sulfur was likely as follows Sorg ≥ Sp ≥ SSO4

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration