When one is not necessarily a lonely number: initial colonization dynamics of Adelges tsugae on eastern hemlock, Tsuga canadensis

The ability to establish successfully in a new area can vary considerably among species. In addition to the well-recognized importance of propagule pressure in driving the rates of establishment of biological invaders, the life history strategy of a species can also affect establishment success, such as in the extent to which Allee effects (positive density-dependence), and environmental and demographic stochasticity manifest themselves. We quantified the establishment success of Adelges tsugae, a non-native insect currently invading North American hemlock. We inoculated eastern hemlock host trees with varying densities of this parthenogenetic insect, from 1 to >500 progrediens ovisacs. The number of settled sistens (the subsequent generation) was positively related to the initial density. More interesting, however, was that we recorded successful establishment from released progrediens ovisacs, and the subsequent initiation of the next generation (sistens), in ≈39 % of host trees inoculated with 1 ovisac. The observation that successful establishment can be accomplished by a single ovisac produced by a single individual has important implications in the invasion dynamics and management of A. tsugae.     

Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: Exploring a new role of haptoglobin in the tumoral microenvironment

Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly “preparing” these cells for the potential induction of the metastatic phenotype.     

Plant domestication slows pest evolution

Agricultural practices such as breeding resistant varieties and pesticide use can cause rapid evolution of pest species, but it remains unknown how plant domestication itself impacts pest contemporary evolution. Using experimental evolution on a comparative phylogenetic scale, we compared the evolutionary dynamics of a globally important economic pest – the green peach aphid (Myzus persicae) – growing on 34 plant taxa, represented by 17 crop species and their wild relatives. Domestication slowed aphid evolution by 13.5%, maintained 10.4% greater aphid genotypic diversity and 5.6% higher genotypic richness. The direction of evolution (i.e. which genotypes increased in frequency) differed among independent domestication events but was correlated with specific plant traits. Individual‐based simulation models suggested that domestication affects aphid evolution directly by reducing the strength of selection and indirectly by increasing aphid density and thus weakening genetic drift. Our results suggest that phenotypic changes during domestication can alter pest evolutionary dynamics.     

Examination of the active secondary structure of the peptide 101.10, an allosteric modulator of the interleukin‐1 receptor,by positional scanning using β‐amino γ‐lactams

The relationship between the conformation and biological activity of the peptide allosteric modulator of the interleukin‐1 receptor 101.10 (D ‐Arg‐D ‐Tyr‐D ‐Thr‐D ‐Val‐D ‐Glu‐D ‐Leu‐D ‐Ala‐NH₂) has been studied using (R)‐ and (S)‐Bgl residues. Twelve Bgl peptides were synthesized using (R)‐ and (S)‐cyclic sulfamidate reagents derived from L ‐ and D ‐aspartic acid in an optimized Fmoc‐compatible protocol for efficient lactam installment onto the supported peptide resin. Examination of these (R)‐ and (S)‐Bgl 101.10 analogs for their potential to inhibit IL‐1β‐induced thymocyte cell proliferation using a novel fluorescence assay revealed that certain analogs exhibited retained and improved potency relative to the parent peptide 101.10. In light of previous reports that Bgl residues may stabilize type II′β‐turn‐like conformations in peptides, CD spectroscopy was performed on selected compounds to identify secondary structure necessary for peptide biological activity. Results indicate that the presence of a fold about the central residues of the parent peptide may be important for activity. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Tracking Single Cells in Live Animals Using a Photoconvertible Near-Infrared Cell Membrane Label

We describe a novel photoconversion technique to track individual cells in vivo using a commercial lipophilic membrane dye, DiR. We show that DiR exhibits a permanent fluorescence emission shift (photoconversion) after light exposure and does not reacquire the original color over time. Ratiometric imaging can be used to distinguish photoconverted from non-converted cells with high sensitivity. Combining the use of this photoconvertible dye with intravital microscopy, we tracked the division of individual hematopoietic stem/progenitor cells within the calvarium bone marrow of live mice. We also studied the peripheral differentiation of individual T cells by tracking the gain or loss of FoxP3-GFP expression, a marker of the immune suppressive function of CD4⁺ T cells. With the near-infrared photoconvertible membrane dye, the entire visible spectral range is available for simultaneous use with other fluorescent proteins to monitor gene expression or to trace cell lineage commitment in vivo with high spatial and temporal resolution.     

Hermitian splines for modeling biological soft tissue systems that exhibit nonlinear force-elongation curves

Numerical simulation of soft tissue mechanical properties is a critical step in developing valuable biomechanical models of live organisms. A cubic Hermitian spline optimization routine is proposed in this paper to model nonlinear experimental force-elongation curves of soft tissues, in particular when modeled as lumped elements. Boundary conditions are introduced to account for the positive definiteness and the particular curvature of the experimental curve to be fitted. The constrained least-square routine minimizes user intervention and optimizes fitting of the experimental data across the whole fitting range. The routine provides coefficients of a Hermitian spline or corresponding knots that are compatible with a number of constraints that are suitable for modeling soft tissue tensile curves. These coefficients or knots may become inputs to user-defined component properties of various modeling software. Splines are particularly advantageous over the well-known exponential model to account for the traction curve flatness at low elongations and to allow for more flexibility in the fitting process. This is desirable as soft tissue models begin to include more complex physical phenomena.     

Polyfunctionality of a DKK1 self-antigen-specific CD8<Superscript>+</Superscript> T lymphocyte clone in lung cancer

Polyfunctionality is the capacity of a T-cell to execute a variety of effector functions mainly mediated by production of cytokines, chemokines, and cytolytic enzymes. Studies in anti-viral immunity have acknowledged the importance of polyfunctionality in the clearance of infections and maintenance of protection. Although accepted in the field, this concept has not been as well characterized in cancer immunology. Here, we report the polyfunctionality profile analysis of a CD8⁺ T-cell clone isolated from a lung cancer patient and directed against Dickkopf-1, a potentially new tumor-associated antigen (TAA). The clone showed Tc1/Th1 effector tendencies confirmed by secretion of cytokines such as IFN-γ, IP-10, MIP-1β, MIP-1α, IL-2, GM-CSF, and expression of cytolytic enzyme granzyme B. This secretion profile is of particular interest in the context of an anti-tumor response. Although secretion of IL-5 and IL-13 was also detected, absence of IL-4 and IL-10 opposes the idea of cytokine-dependent Th1 inhibition. Establishing a comprehensive cytokine secretion profile may help predict T cells’ specific response against a novel TAA in a peptide vaccination context. It may further help in selecting clones with an optimal functional profile from the peripheral blood of cancer patients for expansion and adoptive cell transfer therapy.     

Optimization of triazoles as novel and potent nonphlorizin SGLT2 inhibitors

Previous efforts have led to the identification of a potent, selective, and nonphlorizin based SGLT2 inhibitor 1. This Letter describes efforts to further optimize the potency, microsomal stability, solubility and pharmacokinetic properties of this series of SGLT2 inhibitors. From these efforts, compounds 28 and 32 have improved solubility and pharmacokinetic properties compared to compound 1