GARN: Sampling RNA 3D Structure Space with Game Theory and Knowledge-Based Scoring Strategies

Cellular processes involve large numbers of RNA molecules. The functions of these RNA molecules and their binding to molecular machines are highly dependent on their 3D structures. One of the key challenges in RNA structure prediction and modeling is predicting the spatial arrangement of the various structural elements of RNA. As RNA folding is generally hierarchical, methods involving coarse-grained models hold great promise for this purpose. We present here a novel coarse-grained method for sampling, based on game theory and knowledge-based potentials. This strategy, GARN (Game Algorithm for RNa sampling), is often much faster than previously described techniques and generates large sets of solutions closely resembling the native structure. GARN is thus a suitable starting point for the molecular modeling of large RNAs, particularly those with experimental constraints. GARN is available from: http://garn.lri.fr/.     

Is There a Link between Exertional Heat Stroke and Susceptibility to Malignant Hyperthermia?

Objective

The identification of a predisposition toward malignant hyperthermia (MH) as a risk factor for exertional heat stroke (EHS) remains a matter of debate. Such a predisposition indicates a causal role for MH susceptibility (MHS) after EHS in certain national recommendations and has led to the use of an in vitro contracture test (IVCT) to identify the MHS trait in selected or unselected EHS patients. The aim of this study was to determine whether the MHS trait is associated with EHS.

Methods

EHS subjects in the French Armed Forces were routinely examined for MHS after experiencing an EHS episode. This retrospective study compared the features of IVCT-diagnosed MHS (iMHS) EHS subjects with those of MH-normal EHS patients and MH patients during the 2004–2010 period. MHS status was assessed using the European protocol.

Results

During the study period, 466 subjects (median age 25 years; 31 women) underwent MHS status investigation following an EHS episode. None of the subjects reported previous MH events. An IVCT was performed in 454 cases and was diagnostic of MHS in 45.6% of the study population, of MH susceptibility to halothane in 18.5%, of MH susceptibility to caffeine in 9.9%, and of MH susceptibility to halothane and caffeine in 17.2%. There were no differences in the clinical features, biological features or outcomes of iMHS EHS subjects compared with those of MH-normal or caffeine or halothane MHS subjects without known prior EHS episode. The recurrence rate was 12.7% and was not associated with MH status or any clinical or biological features. iMHS EHS patients exhibited a significantly less informative IVCT response than MH patients.

Conclusions

The unexpected high prevalence of the MHS trait after EHS suggested a latent disturbance of calcium homeostasis that accounted for the positive IVCT results. This study did not determine whether EHS patients have an increased risk of MH, and it could not determine whether MH susceptibility is a risk factor for EHS.     

Evaluation of the Diagnostic Accuracy of a New Dengue IgA Capture Assay (Platelia Dengue IgA Capture,Bio-Rad) for Dengue Infection Detection

Considering the short lifetime of IgA antibodies in serum and the key advantages of antibody detection ELISAs in terms of sensitivity and specificity, Bio-Rad has just developed a new ELISA test based on the detection of specific anti-dengue IgA. This study has been carried out to assess the performance of this Platelia Dengue IgA Capture assay for dengue infection detection. A total of 184 well-characterized samples provided by the French Guiana NRC sera collection (Laboratory of Virology, Institut Pasteur in French Guiana) were selected among samples collected between 2002 and 2013 from patients exhibiting a dengue-like syndrome. A first group included 134 sera from confirmed dengue-infected patients, and a second included 50 sera from non-dengue infected patients, all collected between day 3 and day 15 after the onset of fever. Dengue infection diagnoses were all confirmed using reference assays by direct virological identification using RT-PCR or virus culture on acute sera samples or on paired acute-phase sera samples of selected convalescent sera. This study revealed: i) a good overall sensitivity and specificity of the IgA index test, i.e., 93% and 88% respectively, indicating its good correlation to acute dengue diagnosis; and ii) a good concordance with the Panbio IgM capture ELISA. Because of the shorter persistence of dengue virus-specific IgA than IgM, these results underlined the relevance of this new test, which could significantly improve dengue diagnosis accuracy, especially in countries where dengue virus is (hyper-) endemic. It would allow for additional refinement of dengue diagnostic strategy.     

Synthesis of Novel Thiopurine Pyranonucleosides: Evaluation of Their Bioactivity

We report the synthesis of novel thiopurine pyranonucleosides. Direct coupling of silylated 6-mercaptopurine and 6-thioguanine with the appropriate pyranoses 1a–e via Vorbrüggen nucleosidation, gave the N-9 linked mercaptopurine 2a–e and thioguanine 4a–e nucleosides, while their N-7 substituted congeners 10a–e and 7a–e, were obtained through condensation of the same acetates with 6-chloro and 2-amino-6-chloropurines, followed by subsequent thionation. Nucleosides 3a–e, 5a–e, 8a–e, and 11a–e were evaluated for their cytostatic activity in three different tumor cell proliferative assays.     

Engineering temporal accumulation of a low recalcitrance polysaccharide leads to increased C6 sugar content in plant cell walls

Reduced cell wall recalcitrance and increased C6 monosaccharide content are desirable traits for future biofuel crops, as long as these biomass modifications do not significantly alter normal growth and development. Mixed‐linkage glucan (MLG), a cell wall polysaccharide only present in grasses and related species among flowering plants, is comprised of glucose monomers linked by both β‐1,3 and β‐1,4 bonds. Previous data have shown that constitutive production of MLG in barley (Hordeum vulgare) severely compromises growth and development. Here, we used spatio‐temporal strategies to engineer Arabidopsis thaliana plants to accumulate significant amounts of MLG in the cell wall by expressing the rice CslF6 MLG synthase using secondary cell wall and senescence‐associated promoters. Results using secondary wall promoters were suboptimal. When the rice MLG synthase was expressed under the control of a senescence‐associated promoter, we obtained up to four times more glucose in the matrix cell wall fraction and up to a 42% increase in saccharification compared to control lines. Importantly, these plants grew and developed normally. The induction of MLG deposition at senescence correlated with an increase of gluconic acid in cell wall extracts of transgenic plants in contrast to the other approaches presented in this study. MLG produced in Arabidopsis has an altered structure compared to the grass glucan, which likely affects its solubility, while its molecular size is unaffected. The induction of cell wall polysaccharide biosynthesis in senescing tissues offers a novel engineering alternative to enhance cell wall properties of lignocellulosic biofuel crops.     

Altitudinal variation in fertility and vegetative growth in the invasive plant Rubus alceifolius Poiret (Rosaceae), on Réunion island.

Rubus alceifolius Poiret (Rosaceae) was introduced to the island of Réunion in the southeastern Indian Ocean about 1850 and is now highly invasive. This bramble, native from southeastern Asia and Malaysia, has invaded a wide variety of habitats (lowland rainforest, mountain and submountain rainforest, Acacia heterophylla rainforest) from sea level to 1700 m. It is suspected to be monoclonal so, its remarkable success may be due in part to great phenotypic plasticity. On Réunion, bud, flower, fruit and seed production, the duration of the flowering period and the importance of the seed bank were found to be negatively correlated with elevation (50-1500 m a.s.l.). At a lowland site, fruit production in mature stands averaged between 30 and 80 fruits/m² during 1999 and 2000. No fruit set occurred above 1100 m. This fruit production pattern was similar over two years. Although the number of leaves per unit area is similar along the whole gradient studied, decrease of fruit set in upland areas might be compensated for by an increase in vegetative growth. Temperature variation is very sharp along the elevation gradient and may control the fruit and the seed production. Fruit production allows establishment of new populations all around the island via bird dissemination. Once established, R. alceifolius maintains dense patches that can grow vegetatively. Our results may be relevant for eradication programs that should take into account variation in reproductive strategy in lowland vs. highland habitats.     

A Basis for Spatial and Social Patterns in Ant Species: Dynamics and Mechanisms of Aggregation

Aggregation is usually studied in functional terms, forgetting mechanisms. In this paper, experimental results on the ant Lasius niger, complemented by a model, allow us to understand the mechanisms responsible for aggregation and to study the influence of the population density on this phenomenon. The results show (1) a high level of aggregation and the emergence of a large cluster; (2) that aggregation results from an amplification mechanism—the greater the number of ants inside a cluster, the greater the time spent by one ant in this cluster; and (3) that population density has only a weak influence on the aggregation process. This method of analysis and these results can certainly be extended not only in social insects but also in other species, like subsocial arthropods.