Priority resource access mediates competitive intensity between an invasive weevil and native floral herbivores

Mechanisms underlying invasive species impacts remain incompletely understood. We tested the hypothesis that priority resource access by an invasive biocontrol weevil, Rhinocyllus conicus, intensifies and alters the outcome of competition with native floral herbivores over flower head resources of the non-target, native host plant Cirsium canescens, specifically with the predominant, synchronous tephritid fly Paracantha culta. Four main results emerged. First, we documented strong, asymmetric competition, with R. conicus out-competing P. culta. Second, weevil priority access to floral resources accelerated competitive suppression of P. culta. Evidence for competitive suppression with increased weevil priority included decreases in both the numbers and the total biomass of native flies, plus decreases in individual P. culta fly mass and, so, potential fitness. Third, we found evidence for three concurrent mechanisms underlying the competitive suppression of P. culta by R. conicus. Prior use of a flower head by R. conicus interfered with P. culta pre-oviposition behavior. Once oviposition occurred, the weevil also reduced fly post-oviposition performance. Preemptive resource exploitation occurred, shown by the significant effect of flower head size on the total number of insects developing and in the magnitude of R. conicus effects on P. culta. Interference also occurred, shown by a spatial shift of surviving P. culta individuals away from the preferred receptacle resources as R. conicus priority increased. Finally, fourth, using an individual-based model (IBM), we found that the competitive interactions documented have the potential for imposing demographic consequences, causing a reduction in P. culta population sizes. Thus, priority resource access by an invasive insect increased competitive impact on the predominant native insect in the invaded floral guild. This study also provides the first experimental evidence for non-target effects of a weed biological control agent on an associated native insect herbivore.     

Extracellular ADP is a powerful osteolytic agent: evidence for signaling through the P2Y(1) receptor on bone cells.

There is increasing evidence that extracellular nucleotides act on bone cells via P2 receptors. This study investigated the action of ADP and 2-methylthioADP, a potent ADP analog with selectivity for the P2Y(1) receptor, on osteoclasts, the bone-resorbing multinuclear cells. Using three different assays, we show that ADP and 2-methylthioADP at nanomolar to submicromolar levels caused up to fourfold to sixfold increases in osteoclastic bone resorption. On mature rat osteoclasts, cultured for 1 day on polished dentine disks, peak effects on resorption pit formation were observed between 20 nM and 2 microM of ADP. The same concentrations of ADP also stimulated osteoclast and resorption pit formation in 10-day mouse marrow cultures on dentine disks. In 3-day explant cultures of mouse calvarial bones, the stimulatory effect of ADP on osteoclast-mediated Ca(2+) release was greatest at 5-50 microM and equivalent to the maximal effects of prostaglandin E(2). The ADP effects were blocked in a nontoxic manner by MRS 2179, a P2Y(1) receptor antagonist. Using in situ hybridization and immunocytochemistry, we found evidence for P2Y(1) receptor expression on both osteoclasts and osteoblasts; thus, ADP could exert its actions both directly on osteoclasts and indirectly via P2Y(1) receptors on osteoblasts. As a major ATP degradation product, ADP is a novel stimulator of bone resorption that could help mediate inflammatory bone loss in vivo.     

Bayesian profiling for cost with zeros to decompose total cost into probability of cost and mean nonzero cost

Cost of health care can vary substantially across hospitals, centers, or providers. Data from electronic health records provide information for studying patterns of cost variation and identifying high or low cost centers. Cost data often include zero values when patients receive no care, and joint two-part models have been developed for clustered cost data with zeros. Standard methods for center comparisons, sometimes called profiling, can use these methods to incorporate zero values into total cost. However, zero costs also provide opportunities to further examine sources of cost variation and outliers. For example, a hospital may have high (or low) cost due to frequency of nonzero cost, amount of nonzero cost, or a combination of those. We give methods for decomposing hospital differences in total cost with zeros into components for probability of use (i.e., of nonzero cost) and for cost of use (mean of nonzero cost). The components multiply to total cost and quantify components on the same easily interpreted multiplicative scales. The methods are based on Bayesian hierarchical models and counterfactual arguments, with Markov chain Monte Carlo estimation. We used simulated data to illustrate use, interpretation, and visualization of the methods in diverse situations, and applied the methods to 30,024 patients at 57 US Veterans Administration hospitals to characterize outlier hospitals in one year cost of inpatient care following a cardiac procedure. Twenty eight percent of patients had zero cost. These methods are useful in providing insight into cost variation and outliers for planning future studies or interventions.     

Spatio-temporal cross-correlation analysis of catfish retinal neurons

1. The receptive field properties of visual neurons in the retina of the catfish are studied by a white noise spatio-temporal stimulus. The spatial and temporal inputs of the stimulus are independent and lead to complete linear characterizations and local nonlinear characterizations of the neural response. 2. Horizontal cells, bipolar cells, and sustained or Type N amacrine cells all yield spatially coherent linear correlations. The horizontal cells have the shortest latency by these methods and exhibit a late depolarizing component that is wider in spatial extent than the initial hyperpolarizing component. Depolarizing Type N neurons have center-hyperpolarizing local nonlinearity. 3. Transient or Type C amacrine cells do not correlate well with the intensity of the stimulus, even though the Fast variety responds vigorously to the stimulus. 4. Ganglion cells are classified into Excitatory, Inhibitory and Biphasic classes based upon their linear correlations. Some ganglions exhibit responses dependent upon the orientation of stimulus. Although linear correlation of the Excitatory class is similar to that of the depolarizing Type N cell, the locally nonlinear character of these cell types is distinct. The receptive field of the Inhibitory ganglion cells has strong locally excitatory nonlinearity.     

Synthesis of protoporphyrin IX induced by 5-aminolevulinic acid in yeast cells in the presence of 2,2;-dipyridyl

5-Aminolevulinic acid (ALA), a precursor of porphyrin synthesis, increased the production of various porphyrin compounds in Candida guilliermondii cells. Metalloporphyrins and protoporphyrin IX (PPIX) were predominantly accumulated, respectively, at ALA concentrations of 0.2-0.4 mM and at those higher than 1.5 mM. 2,2;-Dipyridyl which complexed with bivalent metals significantly increased the content of endogenous PPIX even at ALA concentrations lower than 0.5 mM. Under these conditions, the yeast sensitivity to photodynamic effect of visible light (400-600 nm) dramatically increased due to photosensitization by endogenous PPIX.     

Induction of autophagy through CLEC4E in combination with TLR4: an innovative strategy to restrict the survival of Mycobacterium tuberculosis

ABSTRACT

Host-directed therapies are gaining considerable impetus because of the emergence of drug-resistant strains of pathogens due to antibiotic therapy. Therefore, there is an urgent need to exploit alternative and novel strategies directed at host molecules to successfully restrict infections. The C-type lectin receptor CLEC4E and Toll-like receptor TLR4 expressed by host cells are among the first line of defense in encountering pathogens. Therefore, we exploited signaling of macrophages through CLEC4E in association with TLR4 agonists (C₄.T₄) to control the growth of Mycobacterium tuberculosis (Mtb). We observed significant improvement in host immunity and reduced bacterial load in the lungs of Mtb-infected mice and guinea pigs treated with C₄.T₄ agonists. Further, intracellular killing of Mtb was achieved with a 10-fold lower dose of isoniazid or rifampicin in conjunction with C₄.T₄ than the drugs alone. C₄.T₄ activated MYD88, PtdIns3K, STAT1 and RELA/NFKB, increased lysosome biogenesis, decreased Il10 and Il4 gene expression and enhanced macroautophagy/autophagy. Macrophages from autophagy-deficient (atg5 knockout or Becn1 knockdown) mice showed elevated survival of Mtb. The present findings also unveiled the novel role of CLEC4E in inducing autophagy through MYD88, which is required for control of Mtb growth. This study suggests a unique immunotherapeutic approach involving CLEC4E in conjunction with TLR4 to restrict the survival of Mtb through autophagy.     

Regulation of costimulation in the era of butyrophilins

The butyrophilin and butyrophilin-like superfamily of molecules has garnered attention in the immunology world in the past few years as a result of the observation that the butyrophilin-like 2 molecule, BTNL2, can alter T cell responsiveness. Additional interest in this superfamily solidified following the discovery that genetic polymorphisms in BTNL2 are associated with predisposition to many human diseases. In this review, we will provide an overview of the members comprising the butyrophilin superfamily of molecules. We will then discuss BTNL2 immunomodulatory function, and BTNL2 structural associations with other costimulatory molecules. We will then draw your attention to some of the lesser-known butyrophilin superfamily members by describing the expression patterns of these molecules in human tissues and cells. And we will finish by hypothesizing on the potential influence on general immune homeostasis that might be mediated by this, thus-far little-studied, family of molecules.