Soybean Aphid Predators in Québec and the Suitability of Aphis glycines as Prey for Three Coccinellidae

Since its invasion of North America in 2000, the soybean aphid, Aphis glycines Matsumura (Homoptera: Aphididae) has notably changed the arthropod community of the soybean agroecosystem. The objectives of this study were to characterize the foliar predatory fauna associated with A. glycines in commercial soybean fields in Québec, Canada, and to evaluate the suitability of A. glycines as prey for three coccinellid species: Harmonia axyridis Pallas, Propylea quatuordecimpunctata L. and Coleomegilla maculata lengi Timberlake (Coleoptera: Coccinellidae). Field surveys showed that several predators responded rapidly to expanding and increasing populations of the soybean aphid. Coccinellidae were the most important aphidophagous predators observed in 2002 (58.6%) and 2003 (44.8%), with mainly four native and naturalized species co-occurring with the soybean aphid throughout the growing season. Measurement of fitness parameters under laboratory conditions (survival, development time, longevity, fecundity) indicated that A. glycines is an excellent prey for the development and reproduction of all three of the coccinellid species studied. The intrinsic rate of natural increase (r_m) was highest for H. axyridis (0.238 d⁻¹), intermediate for P. quatuordecimpunctata (0.215 d⁻¹) and lowest for C. maculata (0.134 d⁻¹).     

Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages

Invariant natural killer T (iNKT) cells are non-conventional lipid-reactive αβ T lymphocytes that play a key role in host responses during viral infections, in particular through the swift production of cytokines. Their beneficial role during experimental influenza A virus (IAV) infection has recently been proposed, although the mechanisms involved remain elusive. Here we show that during in vivo IAV infection, mouse pulmonary iNKT cells produce IFN-γ and IL-22, a Th17-related cytokine critical in mucosal immunity. Although permissive to viral replication, IL-22 production by iNKT cells is not due to IAV infection per se of these cells but is indirectly mediated by IAV-infected dendritic cells (DCs). We show that activation of the viral RNA sensors TLR7 and RIG-I in DCs is important for triggering IL-22 secretion by iNKT cells, whereas the NOD-like receptors NOD2 and NLRP3 are dispensable. Invariant NKT cells respond to IL-1β and IL-23 provided by infected DCs independently of the CD1d molecule to release IL-22. In vitro, IL-22 protects IAV-infected airway epithelial cells against mortality but has no role on viral replication. Finally, during early IAV infection, IL-22 plays a positive role in the control of lung epithelial damages. Overall, IAV infection of DCs activates iNKT cells, providing a rapid source of IL-22 that might be beneficial to preserve the lung epithelium integrity.     

Discovery of a series of imidazopyrazine small molecule inhibitors of the kinase MAPKAPK5, that show activity using in vitro and in vivo models of rheumatoid arthritis

MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds.     

Bench and mathematical modeling of the effects of breathing a helium/oxygen mixture on expiratory time constants in the presence of heterogeneous airway obstructions

ABSTRACT: BACKGROUND: Expiratory time constants are used to quantify emptying of the lung as a whole, and emptying of individual lung compartments. Breathing low-density helium/oxygen mixtures may modify regional time constants so as to redistribute ventilation, potentially reducing gas trapping and hyperinflation for patients with obstructive lung disease. In the present work, bench and mathematical models of the lung were used to study the influence of heterogeneous patterns of obstruction on compartmental and whole-lung time constants. METHODS: A two-compartment mechanical test lung was used with the resistance in one compartment held constant, and a series of increasing resistances placed in the opposite compartment. Measurements were made over a range of lung compliances during ventilation with air or with a 8/22% mixture of helium/oxygen. The resistance imposed by the breathing circuit was assessed for both gases. Experimental results were compared with predictions of a mathematical model applied to the test lung and breathing circuit. In addition, compartmental and whole-lung time constants were compared with those reported by the ventilator. RESULTS: Time constants were greater for larger minute ventilation, and were reduced by substituting helium/oxygen in place of air. Notably, where time constants were long due to high lung compliance (i.e. low elasticity), helium/oxygen improved expiratory flow even for a low level of resistance representative of healthy, adult airways. In such circumstances, the resistance imposed by the external breathing circuit was significant. Mathematical predictions were in agreement with experimental results. Time constants reported by the ventilator were wellcorrelated with those determined for the whole-lung and for the low-resistance compartment, but poorly correlated with time constants determined for the high-resistance compartment. CONCLUSIONS: It was concluded that breathing a low-density gas mixture, such as helium/oxygen, can improve expiratory flow from an obstructed lung compartment, but that such improvements will not necessarily affect time constants measured by the ventilator. Further research is required to determine if alternative measurements made at the ventilator level are predictive of regional changes in ventilation. It is anticipated that such efforts will be aided by continued development of mathematical models to include pertinent physiological and pathophysiological phenomena that are difficult to reproduce in mechanical test systems.     

Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells

To assess the genetic consequences of induced pluripotent stem cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. We detected hundreds of single nucleotide variants (SNVs) in every clone, with an average of 11 in coding regions. In two experiments, all SNVs were unique for each clone and did not cluster in pathways, but in the third, all four iPSC clones contained 157 shared genetic variants, which could also be detected in rare cells (<1 in 500) within the parental MEF pool. These data suggest that most of the genetic variation in iPSC clones is not caused by reprogramming per se, but is rather a consequence of cloning individual cells, which "captures" their mutational history. These findings have implications for the development and therapeutic use of cells that are reprogrammed by any method.     

Inferring Processes from Spatial Patterns: The Role of Directional and Non–Directional Forces in Shaping Fish Larvae Distribution in a Freshwater Lake System

Larval dispersal is a crucial factor for fish recruitment. For fishes with relatively small-bodied larvae, drift has the potential to play a more important role than active habitat selection in determining larval dispersal; therefore, we expect small-bodied fish larvae to be poorly associated with habitat characteristics. To test this hypothesis, we used as model yellow perch (Perca flavescens), whose larvae are among the smallest among freshwater temperate fishes. Thus, we analysed the habitat association of yellow perch larvae at multiple spatial scales in a large shallow fluvial lake by explicitly modelling directional (e.g. due to water currents) and non-directional (e.g. due to aggregation) spatial patterns. This allowed us to indirectly assess the relative roles of drift (directional process) and potential habitat choice on larval dispersal. Our results give weak support to the drift hypothesis, whereas yellow perch show a strong habitat association at unexpectedly small sizes, when compared to other systems. We found consistent non-directional patterns in larvae distributions at both broad and medium spatial scales but only few significant directional components. The environmental variables alone (e.g. vegetation) generally explained a significant and biologically relevant fraction of the variation in fish larvae distribution data. These results suggest that (i) drift plays a minor role in this shallow system, (ii) larvae display spatial patterns that only partially covary with environmental variables, and (iii) larvae are associated to specific habitats. By suggesting that habitat association potentially includes an active choice component for yellow perch larvae, our results shed new light on the ecology of freshwater fish larvae and should help in building more realistic recruitment models.     

Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations. Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4-67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.     

Chimeric β-Lactamases: Global Conservation of Parental Function and Fast Time-Scale Dynamics with Increased Slow Motions

Enzyme engineering has been facilitated by recombination of close homologues, followed by functional screening. In one such effort, chimeras of two class-A β-lactamases – TEM-1 and PSE-4 – were created according to structure-guided protein recombination and selected for their capacity to promote bacterial proliferation in the presence of ampicillin (Voigt et al., Nat. Struct. Biol. 2002 9:553). To provide a more detailed assessment of the effects of protein recombination on the structure and function of the resulting chimeric enzymes, we characterized a series of functional TEM-1/PSE-4 chimeras possessing between 17 and 92 substitutions relative to TEM-1 β-lactamase. Circular dichroism and thermal scanning fluorimetry revealed that the chimeras were generally well folded. Despite harbouring important sequence variation relative to either of the two ‘parental’ β-lactamases, the chimeric β-lactamases displayed substrate recognition spectra and reactivity similar to their most closely-related parent. To gain further insight into the changes induced by chimerization, the chimera with 17 substitutions was investigated by NMR spin relaxation. While high order was conserved on the ps-ns timescale, a hallmark of class A β-lactamases, evidence of additional slow motions on the µs-ms timescale was extracted from model-free calculations. This is consistent with the greater number of resonances that could not be assigned in this chimera relative to the parental β-lactamases, and is consistent with this well-folded and functional chimeric β-lactamase displaying increased slow time-scale motions.