A Bayesian palaeoenvironmental transfer function model for acidified lakes

A Bayesian approach to palaeoecological environmental reconstruction deriving from the unimodal responses generally exhibited by organisms to an environmental gradient is described. The approach uses Bayesian model selection to calculate a collection of probability-weighted, species-specific response curves (SRCs) for each taxon within a training set, with an explicit treatment for zero abundances. These SRCs are used to reconstruct the environmental variable from sub-fossilised assemblages. The approach enables a substantial increase in computational efficiency (several orders of magnitude) over existing Bayesian methodologies. The model is developed from the Surface Water Acidification Programme (SWAP) training set and is demonstrated to exhibit comparable predictive power to existing Weighted Averaging and Maximum Likelihood methodologies, though with improvements in bias; the additional explanatory power of the Bayesian approach lies in an explicit calculation of uncertainty for each individual reconstruction. The model is applied to reconstruct the Holocene acidification history of the Round Loch of Glenhead, including a reconstruction of recent recovery derived from sediment trap data.The Bayesian reconstructions display similar trends to conventional (Weighted Averaging Partial Least Squares) reconstructions but provide a better reconstruction of extreme pH and are more sensitive to small changes in diatom assemblages. The validity of the posteriors as an apparently meaningful representation of assemblage-specific uncertainty and the high computational efficiency of the approach open up the possibility of highly constrained multiproxy reconstructions

Conformational landscapes of DNA polymerase I and mutator derivatives establish fidelity checkpoints for nucleotide insertion

The fidelity of DNA polymerases depends on conformational changes that promote the rejection of incorrect nucleotides before phosphoryl transfer. Here, we combine single-molecule FRET with the use of DNA polymerase I and various fidelity mutants to highlight mechanisms by which active-site side chains influence the conformational transitions and free-energy landscape that underlie fidelity decisions in DNA synthesis. Ternary complexes of high fidelity derivatives with complementary dNTPs adopt mainly a fully closed conformation, whereas a conformation with a FRET value between those of open and closed is sparsely populated. This intermediate-FRET state, which we attribute to a partially closed conformation, is also predominant in ternary complexes with incorrect nucleotides and, strikingly, in most ternary complexes of low-fidelity derivatives for both correct and incorrect nucleotides. The mutator phenotype of the low-fidelity derivatives correlates well with reduced affinity for complementary dNTPs and highlights the partially closed conformation as a primary checkpoint for nucleotide selection

Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvaline

<p>Abstract</p> <p>Background</p> <p>Pharmacological inhibition of endothelial arginase-II has been shown to improve endothelial nitric oxide synthase (eNOS) function and reduce atherogenesis in animal models. We investigated whether the endothelial arginase II is involved in inflammatory responses in endothelial cells.</p> <p>Methods</p> <p>Human endothelial cells were isolated from umbilical veins and stimulated with TNFα (10 ng/ml) for 4 hours. Endothelial expression of the inflammatory molecules i.e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were assessed by immunoblotting.</p> <p>Results</p> <p>The induction of the expression of endothelial VCAM-1, ICAM-1 and E-selectin by TNFα was concentration-dependently reduced by incubation of the endothelial cells with the arginase inhibitor L-norvaline. However, inhibition of arginase by another arginase inhibitor S-(2-boronoethyl)-L-cysteine (BEC) had no effects. To confirm the role of arginase-II (the prominent isoform expressed in HUVECs) in the inflammatory responses, adenoviral mediated siRNA silencing of arginase-II knocked down the arginase II protein level, but did not inhibit the up-regulation of the adhesion molecules. Moreover, the inhibitory effect of L-norvaline was not reversed by the NOS inhibitor L-NAME and L-norvaline did not interfere with TNFα-induced activation of NF-κB, JNK, p38mapk, while it inhibited p70s6k (S6K1) activity. Silencing S6K1 prevented up-regulation of E-selectin, but not that of VCAM-1 or ICAM-1 induced by TNFα.</p> <p>Conclusion</p> <p>The arginase inhibitor L-norvaline exhibits anti-inflammatory effects independently of inhibition of arginase in human endothelial cells. The anti-inflammatory properties of L-norvaline are partially attributable to its ability to inhibit S6K1.</p

The Beck Cognitive Insight Scale (BCIS): translation and validation of the Taiwanese version

<p>Abstract</p> <p>Background</p> <p>Over the last few decades, research concerning the insight of patients with schizophrenia and its relationships with other clinical variables has been given much attention in the clinical setting. Since that time, a series of instruments assessing insight have been developed. The purpose of this study was to examine the reliability and validity of the Taiwanese version of the Beck Cognitive Insight Scale (BCIS). The BCIS is a self-administered instrument designed to evaluate cognitive processes that involves reevaluating patients' anomalous experiences and specific misinterpretations.</p> <p>Methods</p> <p>The English language version of the BCIS was translated into Taiwanese for use in this study. A total of 180 subjects with and without psychosis completed the Taiwanese version of the BCIS and additional evaluations to assess researcher-rated insight scales and psychopathology. Psychometric properties (factor structures and various types of reliability and validity) were assessed for this translated questionnaire.</p> <p>Results</p> <p>Overall, the Taiwanese version of the BCIS showed good reliability and stability over time. This translated scale comprised a two-factor solution corresponding to reflective attitude and certain attitude subscales. Following the validation of the internal structure of the scale, we obtained an R-C (reflective attitude minus certain attitude) index of the translated BCIS, representing the measurement of cognitive insight by subtracting the score of the certain attitude subscale from that of the reflective attitude subscale. As predicted, the differences in mean reflective attitude, certain attitude and R-C index between subjects with and without psychosis were significant. Our data also demonstrated that psychotic patients were significantly less reflective, more confident in their beliefs, and had less cognitive insight compared with nonpsychotic control groups.</p> <p>Conclusions</p> <p>In light of these findings, we believe that the Taiwanese version of BCIS is a valid and reliable instrument for the assessment of cognitive insight in psychotic patients.</p

Influence of virtual reality soccer game on walking performance in robotic assisted gait training for children

BACKGROUND: Virtual reality (VR) offers powerful therapy options within a functional, purposeful and motivating context. Several studies have shown that patients' motivation plays a crucial role in determining therapy outcome. However, few studies have demonstrated the potential of VR in pediatric rehabilitation. Therefore, we developed a VR-based soccer scenario, which provided interactive elements to engage patients during robotic assisted treadmill training (RAGT). The aim of this study was to compare the immediate effect of different supportive conditions (VR versus non-VR conditions) on motor output in patients and healthy control children during training with the driven gait orthosis Lokomat*. METHODS: A total of 18 children (ten patients with different neurological gait disorders, eight healthy controls) took part in this study. They were instructed to walk on the Lokomat in four different, randomly-presented conditions: (1) walk normally without supporting assistance, (2) with therapists' instructions to promote active participation, (3) with VR as a motivating tool to walk actively and (4) with the VR tool combined with therapists' instructions. The Lokomat gait orthosis is equipped with sensors at hip and knee joint to measure man-machine interaction forces. Additionally, subjects' acceptance of the RAGT with VR was assessed using a questionnaire. RESULTS: The mixed ANOVA revealed significant main effects for the factor CONDITIONS (p < 0.001) and a significant interaction CONDITIONS x GROUP (p = 0.01). Tests of between-subjects effects showed no significant main effect for the GROUP (p = 0.592). Active participation in patients and control children increased significantly when supported and motivated either by therapists' instructions or by a VR scenario compared with the baseline measurement "normal walking" (p < 0.001). CONCLUSIONS: The VR scenario used here induces an immediate effect on motor output to a similar degree as the effect resulting from verbal instructions by the therapists. Further research needs to focus on the implementation of interactive design elements, which keep motivation high across and beyond RAGT sessions, especially in pediatric rehabilitation

How Noisy Adaptation of Neurons Shapes Interspike Interval Histograms and Correlations

Channel noise is the dominant intrinsic noise source of neurons causing variability in the timing of action potentials and interspike intervals (ISI). Slow adaptation currents are observed in many cells and strongly shape response properties of neurons. These currents are mediated by finite populations of ionic channels and may thus carry a substantial noise component. Here we study the effect of such adaptation noise on the ISI statistics of an integrate-and-fire model neuron by means of analytical techniques and extensive numerical simulations. We contrast this stochastic adaptation with the commonly studied case of a fast fluctuating current noise and a deterministic adaptation current (corresponding to an infinite population of adaptation channels). We derive analytical approximations for the ISI density and ISI serial correlation coefficient for both cases. For fast fluctuations and deterministic adaptation, the ISI density is well approximated by an inverse Gaussian (IG) and the ISI correlations are negative. In marked contrast, for stochastic adaptation, the density is more peaked and has a heavier tail than an IG density and the serial correlations are positive. A numerical study of the mixed case where both fast fluctuations and adaptation channel noise are present reveals a smooth transition between the analytically tractable limiting cases. Our conclusions are furthermore supported by numerical simulations of a biophysically more realistic Hodgkin-Huxley type model. Our results could be used to infer the dominant source of noise in neurons from their ISI statistics

Development, standardization and refinement of procedures for evaluating effects of endocrine active compounds on development and sexual differentiation of Xenopus laevis

Xenopus laevis has been introduced as a model to study effects of endocrine-active compounds (EAC) on development and sexual differentiation. However, variable and inconsistent data have raised questions about the reliability of the test methods applied. The current study was conducted in two laboratories to develop, refine, and standardize procedures and protocols. Larvae were exposed in flow-through systems to 17β-estradiol (E2), at concentrations from 0.2 to 6.0 μg E2 L−1 in Experiment 1A, and 0.015 to 2.0 μg E2 L−1 in Experiment 1B. In both studies survival (92%, 99%) and percentage of animals that completed metamorphosis (97%, 99%) indicated reproducible biological performance. Furthermore, minor variations in husbandry led to significant differences in snout-to-vent length, weight, and gonad size. In Experiment 1A, almost complete feminization occurred in all E2 treatment groups whereas a concentration response was observed in Experiment 1B resulting in an EC50 of 0.12 μg E2 L−1. The final verified protocol is suitable for determining effects of EAC on development and sexual differentiation in X. laevis

Knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in Tanzania

Many factors have been mentioned as contributing to under-diagnosis and under-reporting of zoonotic diseases particularly in the sub-Sahara African region. These include poor disease surveillance coverage, poor diagnostic capacity, the geographical distribution of those most affected and lack of clear strategies to address the plight of zoonotic diseases. The current study investigates the knowledge of medical practitioners of zoonotic diseases as a potential contributing factor to their under-diagnosis and hence under-reporting. The study was designed as a cross-sectional survey. Semi-structured open-ended questionnaire was administered to medical practitioners to establish the knowledge of anthrax, rabies, brucellosis, trypanosomiasis, echinococcosis and bovine tuberculosis in selected health facilities within urban and rural settings in Tanzania between April and May 2005. Frequency data were analyzed using likelihood ratio chi-square in Minitab version 14 to compare practitioners' knowledge of transmission, clinical features and diagnosis of the zoonoses in the two settings. For each analysis, likelihood ratio chi-square p-value of less than 0.05 was considered to be significant. Fisher's exact test was used where expected results were less than five. Medical practitioners in rural health facilities had poor knowledge of transmission of sleeping sickness and clinical features of anthrax and rabies in humans compared to their urban counterparts. In both areas the practitioners had poor knowledge of how echinococcosis is transmitted to humans, clinical features of echinococcosis in humans, and diagnosis of bovine tuberculosis in humans. Knowledge of medical practitioners of zoonotic diseases could be a contributing factor to their under-diagnosis and under-reporting in Tanzania. Refresher courses on zoonotic diseases should be conducted particularly to practitioners in rural areas. More emphasis should be put on zoonotic diseases in teaching curricula of medical practitioners' training institutions in Tanzania to improve the diagnosis, reporting and control of zoonotic diseases. Veterinary and medical collaboration should be strengthened to enable more effective control of zoonotic diseases in Tanzania

Managing peatland vegetation for drinking water treatment

Peatland ecosystem services include drinking water provision, flood mitigation, habitat provision and carbon sequestration. Dissolved organic carbon (DOC) removal is a key treatment process for the supply of potable water downstream from peat-dominated catchments. A transition from peat-forming Sphagnum moss to vascular plants has been observed in peatlands degraded by (a) land management, (b) atmospheric deposition and (c) climate change. Here within we show that the presence of vascular plants with higher annual above-ground biomass production leads to a seasonal addition of labile plant material into the peatland ecosystem as litter recalcitrance is lower. The net effect will be a smaller litter carbon pool due to higher rates of decomposition, and a greater seasonal pattern of DOC flux. Conventional water treatment involving coagulation-flocculation-sedimentation may be impeded by vascular plant-derived DOC. It has been shown that vascular plant-derived DOC is more difficult to remove via these methods than DOC derived from Sphagnum, whilst also being less susceptible to microbial mineralisation before reaching the treatment works. These results provide evidence that practices aimed at re-establishing Sphagnum moss on degraded peatlands could reduce costs and improve efficacy at water treatment works, offering an alternative to ‘end-of-pipe’ solutions through management of ecosystem service provision