Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum

BACKGROUND: The carbon metabolism of the blood stages of Plasmodium falciparum, comprising rapidly dividing asexual stages and non-dividing gametocytes, is thought to be highly streamlined, with glycolysis providing most of the cellular ATP. However, these parasitic stages express all the enzymes needed for a canonical mitochondrial tricarboxylic acid (TCA) cycle, and it was recently proposed that they may catabolize glutamine via an atypical branched TCA cycle. Whether these stages catabolize glucose in the TCA cycle and what is the functional significance of mitochondrial metabolism remains unresolved. RESULTS: We reassessed the central carbon metabolism of P. falciparum asexual and sexual blood stages, by metabolically labeling each stage with (13)C-glucose and (13)C-glutamine, and analyzing isotopic enrichment in key pathways using mass spectrometry. In contrast to previous findings, we found that carbon skeletons derived from both glucose and glutamine are catabolized in a canonical oxidative TCA cycle in both the asexual and sexual blood stages. Flux of glucose carbon skeletons into the TCA cycle is low in the asexual blood stages, with glutamine providing most of the carbon skeletons, but increases dramatically in the gametocyte stages. Increased glucose catabolism in the gametocyte TCA cycle was associated with increased glucose uptake, suggesting that the energy requirements of this stage are high. Significantly, whereas chemical inhibition of the TCA cycle had little effect on the growth or viability of asexual stages, inhibition of the gametocyte TCA cycle led to arrested development and death. CONCLUSIONS: Our metabolomics approach has allowed us to revise current models of P. falciparum carbon metabolism. In particular, we found that both asexual and sexual blood stages utilize a conventional TCA cycle to catabolize glucose and glutamine. Gametocyte differentiation is associated with a programmed remodeling of central carbon metabolism that may be required for parasite survival either before or after uptake by the mosquito vector. The increased sensitivity of gametocyte stages to TCA-cycle inhibitors provides a potential target for transmission-blocking drugs

Multiple courses of stereotactic re-irradiation in recurrent oligodendroglioma: a case report

INTRODUCTION: High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit. CASE PRESENTATION: In this report, we describe a 37-year-old Caucasian male initially diagnosed with a grade IV oligodendroglioma, who received multiple courses of re-irradiation and experienced a survival of 10 years with minimal cognitive or neurologic deficits. CONCLUSION: Significant toxicity with multiple courses of radiation does not always occur. Re-irradiation should be considered in a salvage setting

Gravitational waves from binary supermassive black holes missing in pulsar observations.

This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aab1910Gravitational waves are expected to be radiated by supermassive black hole binaries formed during galaxy mergers. A stochastic superposition of gravitational waves from all such binary systems would modulate the arrival times of pulses from radio pulsars. Using observations of millisecond pulsars obtained with the Parkes radio telescope, we constrained the characteristic amplitude of this background, A(c,yr), to be <1.0 × 10(-15) with 95% confidence. This limit excludes predicted ranges for A(c,yr) from current models with 91 to 99.7% probability. We conclude that binary evolution is either stalled or dramatically accelerated by galactic-center environments and that higher-cadence and shorter-wavelength observations would be more sensitive to gravitational waves.The PPTA project was initiated with support from R.N.M.’s Australian Research Council (ARC) Federation Fellowship (grant FF0348478) and from CSIRO under that fellowship program. The PPTA project has also received support from ARC through Discovery Project grants DP0985272 and DP140102578. N.D.R.B. acknowledges support from a Curtin University research fellowship. G.H. and Y.L. are recipients of ARC Future Fellowships (respectively, grants FT120100595 and FT110100384). S.O. is supported by the Alexander von Humboldt Foundation. R.M.S. acknowledges travel support from CSIRO through a John Philip Award for excellence in early-career research. The authors declare no conflicts of interest. Data used in this analysis can be accessed via the Australian National Data Service (www.ands.org.au)

Time-Course Analysis of Cyanobacterium Transcriptome: Detecting Oscillatory Genes

The microarray technique allows the simultaneous measurements of the expression levels of thousands of mRNAs. By mining these data one can identify the dynamics of the gene expression time series. The detection of genes that are periodically expressed is an important step that allows us to study the regulatory mechanisms associated with the circadian cycle. The problem of finding periodicity in biological time series poses many challenges. Such challenge occurs due to the fact that the observed time series usually exhibit non-idealities, such as noise, short length, outliers and unevenly sampled time points. Consequently, the method for finding periodicity should preferably be robust against such anomalies in the data. In this paper, we propose a general and robust procedure for identifying genes with a periodic signature at a given significance level. This identification method is based on autoregressive models and the information theory. By using simulated data we show that the suggested method is capable of identifying rhythmic profiles even in the presence of noise and when the number of data points is small. By recourse of our analysis, we uncover the circadian rhythmic patterns underlying the gene expression profiles from Cyanobacterium Synechocystis

Barriers and supports to implementation of MDI/spacer use in nine Canadian pediatric emergency departments: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Despite recent research supporting the use of metered dose inhalers with spacer devices (MDI/spacers) in pediatric emergency departments (PEDs) for acute exacerbations of asthma, uptake of this practice has been slow. The objectives of this study were to determine the barriers and supports to implementing MDI/spacer research and to identify factors associated with early and late adoption of MDI/spacers in Canadian PEDs.</p> <p>Methods</p> <p>Using a comparative case study design, we classified nine tertiary care pediatric hospital PEDs based on their stage of implementation. Data were collected using focus group interviews with physicians, registered nurses (RNs), and respiratory therapists (RTs), and individual interviews with both patient care and medical directors at each site. Initial coding was based on the Ottawa Model of Research Use (OMRU) categories of elements known to influence the uptake of innovations.</p> <p>Results</p> <p>One hundred and fifty healthcare professionals from nine different healthcare institutions participated in this study. Lack of leadership in the form of a research champion, a lack of consensus about the benefits of MDI/spacers among staff, perceived resistance from patients/parents, and perceived increased cost and workload associated with MDI/spacer use were the most prevalent barriers to the adoption of the MDI/spacer. Common strategies used by early-adopting sites included the active participation of all professional groups in the adoption process in addition to a well-planned and executed educational component for staff, patients, and families. Early adopter sites were also more likely to have the MDI/spacer included in a clinical protocol/pathway.</p> <p>Conclusion</p> <p>Potential barriers and supports to implementation have been identified that will help EDs adopt MDI/spacer use. Future interventions intended to increase MDI/spacer use in PEDs will need to be sensitive to the barriers identified in this study.</p

The quest for the solar g modes

Solar gravity modes (or g modes) -- oscillations of the solar interior for which buoyancy acts as the restoring force -- have the potential to provide unprecedented inference on the structure and dynamics of the solar core, inference that is not possible with the well observed acoustic modes (or p modes). The high amplitude of the g-mode eigenfunctions in the core and the evanesence of the modes in the convection zone make the modes particularly sensitive to the physical and dynamical conditions in the core. Owing to the existence of the convection zone, the g modes have very low amplitudes at photospheric levels, which makes the modes extremely hard to detect. In this paper, we review the current state of play regarding attempts to detect g modes. We review the theory of g modes, including theoretical estimation of the g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the techniques that have been used to try to detect g modes. We review results in the literature, and finish by looking to the future, and the potential advances that can be made -- from both data and data-analysis perspectives -- to give unambiguous detections of individual g modes. The review ends by concluding that, at the time of writing, there is indeed a consensus amongst the authors that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie

Social and Structural Factors Associated with HIV Infection among Female Sex Workers Who Inject Drugs in the Mexico-US Border Region

BACKGROUND: FSWs who inject drugs (FSW-IDUs) can acquire HIV through high risk sexual and injection behaviors. We studied correlates of HIV infection among FSW-IDUs in northern Mexico, where sex work is quasi-legal and syringes can be legally obtained without a prescription. METHODS: FSW-IDUs>18 years old who reported injecting drugs and recent unprotected sex with clients in Tijuana and Ciudad Juarez underwent surveys and HIV/STI testing. Logistic regression identified correlates of HIV infection. RESULTS: Of 620 FSW-IDUs, prevalence of HIV, gonorrhea, Chlamydia, trichomonas, syphilis titers ≥1:8, or any of these infections was 5.3%, 4%, 13%, 35%, 10% and 72%, respectively. Compared to other FSW-IDUs, HIV-positive women were more likely to: have syphilis titers ≥1:8 (36% vs. 9%, p<0.001), often/always inject drugs with clients (55% vs. 32%, p = 0.01), and experience confiscation of syringes by police (49% vs. 28%, p = 0.02). Factors independently associated with HIV infection were syphilis titers ≥1:8, often/always injecting with clients and police confiscation of syringes. Women who obtained syringes from NEPs (needle exchange programs) within the last month had lower odds of HIV infection associated with active syphilis, but among non-NEP attenders, the odds of HIV infection associated with active syphilis was significantly elevated. CONCLUSIONS: Factors operating in both the micro-social environment (i.e., injecting drugs with clients) and policy environment (i.e., having syringes confiscated by police, attending NEPs) predominated as factors associated with risk of HIV infection, rather than individual-level risk behaviors. Interventions should target unjustified policing practices, clients' risk behaviors and HIV/STI prevention through NEPs

Mesoporous monoliths of inverse bicontinuous cubic phases of block copolymer bilayers

Solution self-assembly of block copolymers into inverse bicontinuous cubic mesophases is a promising new approach for creating porous polymer films and monoliths with highly organized bicontinuous mesoporous networks. Here we report the direct self-assembly of block copolymers with branched hydrophilic blocks into large monoliths consisting of the inverse bicontinuous cubic structures of the block copolymer bilayer. We suggest a facile and scalable method of solution self-assembly by diffusion of water to the block copolymer solution, which results in the unperturbed formation of mesoporous monoliths with large-pore (&gt;25nm diameter) networks weaved in crystalline lattices. The surface functional groups of the internal large-pore networks are freely accessible for large guest molecules such as protein complexes of which the molecular weight exceeded 100kDa. The internal double-diamond (Pn3m) networks of large pores within the mesoporous monoliths could be replicated to self-supporting three-dimensional skeletal structures of crystalline titania and mesoporous silica.open2

Is there a role for workplaces in reducing employees' driving to work? Findings from a cross-sectional survey from inner-west Sydney, Australia

<p>Abstract</p> <p>Background</p> <p>The role of workplaces in promoting active travel (walking, cycling or using public transport) is relatively unexplored. This study explores the potential for workplaces to reduce employees' driving to work in order to inform the development of workplace interventions for promoting active travel.</p> <p>Methods</p> <p>An analysis of a cross-sectional survey was conducted using data from parents/guardians whose children participated in the Central Sydney Walk to School Program in inner-west Sydney, Australia. A total of 888 parents/guardians who were employed and worked outside home were included in this analysis. The role of the workplace in regards to active travel was assessed by asking the respondents' level of agreement to eight statements including workplace encouragement of active travel, flexible working hours, public transport availability, convenient parking, shower and change rooms for employees and whether they lived or worked in a safe place. Self-reported main mode of journey to work and demographic data were collected through a self-administrated survey. Binary logistic regression modelling was used to ascertain independent predictors of driving to work.</p> <p>Results</p> <p>Sixty nine per cent of respondents travelled to work by car, and 19% agreed with the statement, "My workplace encourages its employees to go to and from work by public transport, cycling and/or walking (active travel)." The survey respondents with a workplace encouraging active travel to work were significantly less likely to drive to work (49%) than those without this encouragement (73%) with an adjusted odds ratio (AOR) of 0.41 (95% CI 0.23-0.73, P = 0.002). Having convenient public transport close to the workplace or home was also an important factor that could discourage employees from driving to work with AOR 0.17 (95% CI 0.09-0.31, P < 0.0001) and AOR 0.50 (95% CI 0.28-0.90, P = 0.02) respectively. In contrast, convenient parking near the workplace significantly increased the likelihood of respondents driving to work (AOR 4.6, 95% CI 2.8-7.4, P < 0.0001).</p> <p>Conclusions</p> <p>There is a significant inverse association between the perception of workplace encouragement for active travel and driving to work. Increases in the number of workplaces that encourage their employees to commute to work via active travel could potentially lead to fewer employees driving to work. In order to make active travel more appealing than driving to work, workplace interventions should consider developing supportive workplace policies and environments.</p