A Functional Genomics Approach to Tanshinone Biosynthesis Provides Stereochemical Insights

Tanshinones are abietane-type norditerpenoid quinone natural products that are the bioactive components of the Chinese medicinal herb Salvia miltiorrhiza Bunge. The initial results from a functional genomics-based investigation of tanshinone biosynthesis, specifically the functional identification of the relevant diterpene synthases from S. miltiorrhiza, are reported. The cyclohexa-1,4-diene arrangement of the distal ring poises the resulting miltiradiene for the ensuing aromatization and hydroxylation to ferruginol suggested for tanshinone biosynthesis

Combined endo-β-1,4-xylanase and α-L-arabinofuranosidase increases butyrate concentration during broiler cecal fermentation of maize glucurono-arabinoxylan

Solubilisation of prebiotic arabinoxylooligosaccharides from complex arabinoxylans in e.g. maize by xylanases may be increased by addition of auxiliary debranching enzymes. In this study, the hydrolysis and fermentation of maize fibre was investigated in vitro using a xylanase and an alpha-L-arabinofuranosidase. Combining the enzymes induced a higher (P < .001) xylose solubilisation and higher (P < .05) butyrate production during in vitro fermentation of maize fibre with cecal broiler inoculum compared to applying enzymes separately after 48 h. Subsequently, fibre degradation and fermentation was investigated in ROSS 308 broiler chickens supplemented with the enzyme combination to test the effects on gut morphology and microbiota composition along with performance. However, to address the relevance of combining the enzymes in vivo, further full factorial studies using individual enzymes at lower dosages are needed. Birds were fed a maize/soy based diet with 100 g/kg maize DDGS and 50 g/kg rapeseed meal. Enzymes supplementation increased (P < .001) body weight (+ 5.4%) and improved (P < .001) feed conversion ratio (-5.8%) after 29 days compared to control birds. Non-starch polysaccharide analysis and confocal microscopy of jejunum digesta visualised and confirmed solubilisation of the insoluble maize (glucurono)arabinoxylan. Birds receiving enzyme supplementation had increased (P < .001) duodenum villi length (+120 mu m) and reduced (P < .002) CD3 T-cell infiltration (-22.1%) after 29 days. Cecal butyrate levels were increased (P < .05) compared to controls. Although the microbiota composition was not significantly altered, numerical increases in cecal Ruminococcaceae and Lachnospiraceae genera were observed in birds supplemented with enzymes

Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy

PURPOSE To investigate the added value and diagnostic accuracy of 68Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa). METHODS Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a "best valuable comparator" using all available imaging and clinical follow-up as a reference. RESULTS In total, 112 patients were included; 68Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93-0.96, positive predictive value of 0.74-0.81, and negative predictive value of 1.00. 68Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions. CONCLUSION 68Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings

Zero-order filter for diffractive focusing of de Broglie matter waves

The manipulation of neutral atoms and molecules via their de Broglie wave properties, also referred to as de Broglie matter wave optics, is relevant for several fields ranging from fundamental quantum mechanics tests and quantum metrology to measurements of interaction potentials and new imaging techniques. However, there are several challenges. For example, for diffractive focusing elements, the zero-order beam provides a challenge because it decreases the signal contrast. Here we present the experimental realization of a zero-order filter, also referred to as an order-sorting aperture for de Broglie matter wave diffractive focusing elements. The zero-order filter makes it possible to measure even at low beam intensities. We present measurements of zero-order filtered, focused, neutral helium beams generated at source stagnation pressures between 11 and 81 bars. We show that for certain conditions the atom focusing at lower source stagnation pressures (broader velocity distributions) is better than what has previously been predicted. We present simulations with the software ray-tracing simulation package mcstas using a realistic helium source configuration, which gives very good agreement with our measurements

Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders

Considering the role of cognitive control in expert performance

© 2014, Springer Science+Business Media Dordrecht. Dreyfus and Dreyfus’ (1986) influential phenomenological analysis of skill acquisition proposes that expert performance is guided by non-cognitive responses which are fast, effortless and apparently intuitive in nature. Although this model has been criticised (e.g., by Breivik Journal of Philosophy of Sport, 34, 116–134 2007, Journal of the Philosophy of Sport, 40, 85–106 2013; Eriksen 2010; Montero Inquiry:An interdisciplinary Journal of Philosophy, 53, 105–122 2010; Montero and Evans 2011) for over-emphasising the role that intuition plays in facilitating skilled performance, it does recognise that on occasions (e.g., when performance goes awry for some reason) a form of ‘detached deliberative rationality’ may be used by experts to improve their performance. However, Dreyfus and Dreyfus (1986) see no role for calculative problem solving or deliberation (i.e., drawing on rules or mental representations) when performance is going well. In the current paper, we draw on empirical evidence, insights from athletes, and phenomenological description to argue that ‘continuous improvement’ (i.e., the phenomenon whereby certain skilled performers appear to be capable of increasing their proficiency even though they are already experts; Toner and Moran 2014) among experts is mediated by cognitive (or executive) control in three distinct sporting situations (i.e., in training, during pre-performance routines, and while engaged in on-line skill execution). We conclude by arguing that Sutton et al. Journal of the British Society for Phenomenology, 42, 78–103 (2011) ‘applying intelligence to the reflexes’ (AIR) approach may help to elucidate the process by which expert performers achieve continuous improvement through analytical/mindful behaviour during training and competition

Rapid syndromic PCR testing in patients with respiratory tract infections reduces time to results and improves microbial yield

Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus) and explores the feasibility of evaluation in a randomised controlled trial. Patients presenting to hospital with suspected CAP were recruited in a prospective feasibility study. An induced sputum or an endotracheal aspirate was obtained from all participants. The FAP plus turnaround time (TAT) and microbiological yield were compared with standard diagnostic methods (SDs). 96/104 (92%) enrolled patients had a respiratory tract infection (RTI); 72 CAP and 24 other RTIs. Median TAT was shorter for the FAP plus, compared with in-house PCR (2.6 vs 24.1 h, p < 0.001) and sputum cultures (2.6 vs 57.5 h, p < 0.001). The total microbiological yield by the FAP plus was higher compared to SDs (91% (162/179) vs 55% (99/179), p < 0.0001). Haemophilus influenzae, Streptococcus pneumoniae and influenza A virus were the most frequent pathogens. In conclusion, molecular panel testing in adults with CAP was associated with a significant reduction in time to actionable results and increased microbiological yield. The impact on antibiotic use and patient outcome should be assessed in randomised controlled trials.publishedVersio

New measurement of exotic decay of 225^{225}Ac by 14^{14}C emission

The branching ratio of $^{225}$Ac decay by emission of $^{14}$C was remeasured under improved experimental conditions by using a radioactive source produced at the ISOLDE mass-separator at CERN and a nuclear track detector technique. The result, B=$\lambda_{^{14}\textrm{C}} / \lambda_{\alpha} = (4.5 \pm 1.4) 10^{-12}$, is consistent with the anomalously high value obtained in the 1993 experiment thus confirming the importance of nuclear structure effects in this exotic decay