Behavioral response of dissimilatory perchlorate-reducing bacteria to different electron acceptors

The response behavior of three dissimilatory perchlorate-reducing bacteria to different electron acceptors (nitrate, chlorate, and perchlorate) was investigated with two different assays. The observed response was species-specific, dependent on the prior growth conditions, and was inhibited by oxygen. We observed attraction toward nitrate when Dechloromonas aromatica strain RCB and Azospira suillum strain PS were grown with nitrate. When D. aromatica and Dechloromonas agitata strain CKB were grown with perchlorate, both responded to nitrate, chlorate, and perchlorate. When A. suillum was grown with perchlorate, the organism responded to chlorate and perchlorate but not nitrate. A gene replacement mutant in the perchlorate reductase subunit (pcrA) of D. aromatica resulted in a loss of the attraction response toward perchlorate but had no impact on the nitrate response. Washed-cell suspension studies revealed that the perchlorate grown cells of D. aromatica reduced both perchlorate and nitrate, while A. suillum cells reduced perchlorate only. Based on these observations, energy taxis was proposed as the underlying mechanism for the responses to (per)chlorate by D. aromatica. To the best of our knowledge, this study represents the first investigation of the response behavior of perchlorate-reducing bacteria to environmental stimuli. It clearly demonstrates attraction toward chlorine oxyanions and the unique ability of these organisms to distinguish structurally analogous compounds, nitrate, chlorate, and perchlorate and respond accordingly

A review of trisomy X (47,XXX)

Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and adolescents benefit from a psychological evaluation with an emphasis on identifying and developing an intervention plan for problems in cognitive/academic skills, language, and/or social-emotional development. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated for POF. Patients should be referred to support organizations to receive individual and family support. The prognosis is variable, depending on the severity of the manifestations and on the quality and timing of treatment

Determination of masses of the central black holes in NGC524 and NGC2549 using Laser Guide Star Adaptive Optics

[abridged] We present observations of NGC524 and NGC2549 with LGS AO obtained at GEMINI North telescope using the NIFS IFU in the K band. The purpose of these observations, together with previously obtained observations with the SAURON IFU, is to determine the masses (Mbh) of the supermassive black holes (SMBH). The targeted galaxies were chosen to have central light profiles showing a core (NGC524) and a cusp (NGC2549), to probe the feasibility of using the galaxy centre as the NGS required for LGS AO. We employ an innovative `open loop' technique. The data have spatial resolution of 0.23" and 0.17" FWHM, showing that high quality LGS AO observations of these objects are possible. We construct axisymmetric three-integral dynamical models which are constrained with both the NIFS and SAURON data. The best fitting models yield Mbh=(8.3 +2.7 -1.3) x 10^8 Msun for NGC524 and Mbh=(1.4 +0.2 -1.3) x 10^7 Msun for NGC2549 (all errors are at the 3 sigma CL). We demonstrate that the wide-field SAURON data play a crucial role in the M/L determination increasing the accuracy of M/L by a factor of at least 5, and constraining the upper limits on Mbh. The NIFS data are crucial in constraining the lower limits of Mbh and in combination with the large scale data reducing the uncertainty by a factor of 2 or more. We find that the orbital structure of NGC524 shows significant tangential anisotropy, while at larger radii both galaxies are consistent with having almost perfectly oblate velocity ellipsoids. Tangential anisotropy in NGC524 coincides with the size of SMBH sphere of influence and the core region in the light profile. We test the accuracy to which Mbh can be measured using seeings obtained from typical LGS AO observations, and conclude that for a typical conditions and Mbh the expected uncertainty is of the order of 50%.Comment: 19 pages, 14 figure

Illustrating risk difference and number needed to treat from a randomized controlled trial of spinal manipulation for cervicogenic headache

<p>Abstract</p> <p>Background</p> <p>The number needed to treat (NNT) for one participant to benefit is considered a useful, clinically meaningful way of reporting binary outcomes from randomized trials. Analysis of continuous data from our randomized controlled trial has previously demonstrated a significant and clinically important difference favoring spinal manipulation over a light massage control.</p> <p>Methods</p> <p>Eighty participants were randomized to receive spinal manipulation or a light massage control (n = 40/group). Improvements in cervicogenic headache pain (primary outcome), disability, and number in prior four weeks were dichotomized into binary outcomes at two thresholds: 30% representing minimal clinically important change and 50% representing clinical success. Groups were compared at 12 and 24-week follow-up using binomial regression (generalized linear models) to compute the adjusted risk difference (RD) between groups and number needed to treat (NNT) after adjusting for baseline differences between groups. Results were compared to logistic regression results.</p> <p>Results</p> <p>For headache pain, clinically important improvement (30% or 50%) was more likely for spinal manipulation: adjusted RD = 17% to 27% and NNT = 3.8 to 5.8 (p = .005 to .028). Some statistically significant results favoring manipulation were found for headache disability and number.</p> <p>Conclusion</p> <p>Spinal manipulation demonstrated a benefit in terms of a clinically important improvement of cervicogenic headache pain. The use of adjusted NNT is recommended; however, adjusted RD may be easier to interpret than NNT. The study demonstrated how results may depend on the threshold for dichotomizing variables into binary outcomes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NLM identifier NCT00246350.</p

Transactional paths between children and parents in pediatric asthma: Associations between family relationships and adaptation

Introduction. The particular challenges posed by pediatric asthma may have a negative impact on the adaptation of children and their parents. From a transactional approach it is important to examine how reciprocal links between children and parents contribute to explain their adaptation and under which conditions these associations occur. This cross-sectional study aimed at examining the direct and indirect links between children’s and parents’ perceptions of family relationships and adaptation, separately (within-subjects) and across participants (cross-lagged effects), and the role of asthma severity in moderating these associations. Method. The sample comprised 257 children with asthma, aged between 8 and 18 years-old, and one of their parents. Both family members completed self-reported questionnaires on family relationships (cohesion and expressiveness) and adaptation indicators (quality of life and psychological functioning). Physicians assessed asthma severity. Structural Equation Modeling was used to test within-subjects and cross-lagged paths between children’s and parents’ family relationships and adaptation. Results. The model explained 47% of children’s and 30% of parents’ adaptation: family relationships were positively associated with adaptation, directly for children and parents, and indirectly across family members. Asthma severity moderated the association between family relationships and health-related quality of life for children: stronger associations were observed in the presence of persistent asthma. Conclusion. These results highlight the need of including psychological interventions in pediatric healthcare focused on family relationships as potential targets for improving children’s and parents’ quality of life and psychological functioning, and identified the children with persistent asthma as a group that would most benefit from family-based interventions.This study was supported by the R&D Unit Institute of Cognitive Psychology, Vocational and Social Development of the University of Coimbra (PEst-OE/PSI/UI0192/2011) and by the Portuguese Foundation for Science and Technology (PhD Grant SFRH/BD/69885/2010)

Allelic Exchange of Pheromones and Their Receptors Reprograms Sexual Identity in Cryptococcus neoformans

Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining “sexes” known as mating types and is controlled by components of mating type (MAT) loci. MAT–encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and α) that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a) replaced the pheromone and pheromone receptor of the other (α). We discovered that these “αa” cells effectively adopt a new mating type (that of a cells); they sense and respond to α factor, they elicit a mating response from α cells, and they fuse with α cells. In addition, αa cells lose the α cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between α and αa strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT–encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen

A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds

BACKGROUND: Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. METHODOLOGY: We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. CONCLUSIONS: This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking

Examining the BMI-mortality relationship using fractional polynomials

<p>Abstract</p> <p>Background</p> <p>Many previous studies estimating the relationship between body mass index (BMI) and mortality impose assumptions regarding the functional form for BMI and result in conflicting findings. This study investigated a flexible data driven modelling approach to determine the nonlinear and asymmetric functional form for BMI used to examine the relationship between mortality and obesity. This approach was then compared against other commonly used regression models.</p> <p>Methods</p> <p>This study used data from the National Health Interview Survey, between 1997 and 2000. Respondents were linked to the National Death Index with mortality follow-up through 2005. We estimated 5-year all-cause mortality for adults over age 18 using the logistic regression model adjusting for BMI, age and smoking status. All analyses were stratified by sex. The multivariable fractional polynomials (MFP) procedure was employed to determine the best fitting functional form for BMI and evaluated against the model that includes linear and quadratic terms for BMI and the model that groups BMI into standard weight status categories using a deviance difference test. Estimated BMI-mortality curves across models were then compared graphically.</p> <p>Results</p> <p>The best fitting adjustment model contained the powers -1 and -2 for BMI. The relationship between 5-year mortality and BMI when estimated using the MFP approach exhibited a J-shaped pattern for women and a U-shaped pattern for men. A deviance difference test showed a statistically significant improvement in model fit compared to other BMI functions. We found important differences between the MFP model and other commonly used models with regard to the shape and nadir of the BMI-mortality curve and mortality estimates.</p> <p>Conclusions</p> <p>The MFP approach provides a robust alternative to categorization or conventional linear-quadratic models for BMI, which limit the number of curve shapes. The approach is potentially useful in estimating the relationship between the full spectrum of BMI values and other health outcomes, or costs.</p

The Contribution of Social Networks to the Health and Self-Management of Patients with Long-Term Conditions: A Longitudinal Study

Evidence for the effectiveness of patient education programmes in changing individual self-management behaviour is equivocal. More distal elements of personal social relationships and the availability of social capital at the community level may be key to the mobilisation of resources needed for long-term condition self-management to be effective. Aim: To determine how the social networks of people with long-term conditions (diabetes and heart disease) are associated with health-related outcomes and changes in outcomes over time. Methods: Patients with chronic heart disease (CHD) or diabetes (n = 300) randomly selected from the disease registers of 19 GP practices in the North West of England. Data on personal social networks collected using a postal questionnaire, alongside face-to-face interviewing. Follow-up at 12 months via postal questionnaire using a self-report grid for network members identified at baseline. Analysis: Multiple regression analysis of relationships between health status, self-management and health economics outcomes, and characteristics of patients’ social networks. Results: Findings indicated that: (1) social involvement with a wider variety of people and groups supports personal self-management and physical and mental well-being; (2) support work undertaken by personal networks expands in accordance with health needs helping people to cope with their condition; (3) network support substitutes for formal care and can produce substantial saving in traditional health service utilisation costs. Health service costs were significantly (p0.01) reduced for patients receiving greater levels of illness work through their networks. Conclusions: Support for self-management which achieves desirable policy outcomes should be construed less as an individualised set of actions and behaviour and more as a social network phenomenon. This study shows the need for a greater focus on harnessing and sustaining the capacity of networks and the importance of social involvement with community groups and resources for producing a more desirable and cost-effective way of supporting long term illness management