Color and pigment polymorphisms of northern leopard frogs on a prairie landscape

Variation allows populations to adapt to changing conditions. As human activities continue to alter environments and evolutionary processes, it becomes increasingly important to conserve standing genetic variation. Despite technical advances in population genetics, it is still useful to have inexpensive methods of detecting and monitoring genetic variation, particularly in traits that potentially influence fitness. In the Northern Leopard Frog, Lithobates pipiens (= Rana pipiens), genetically determined color (green [dominant: G] or brown [recessive: g]) and two pigment pattern polymorphisms (Burnsi/spotless [B] or spotted [b]; Kandiyohi/mottled [K] or non-mottled[k]) are hypothesized to have adaptive benefits. We assessed spatiotemporal patterns of these polymorphisms during two time periods in one of the largest remaining grasslands in North America. The frequency of the dominant green phenotype remained consistent from the early-to-late 2000s; however, we observed Kandiyohi phenotypes more frequently during 2001–2002 compared to 2009–2010. By contrast, we observed dominant Burnsi phenotypes more frequently in the latter time period. Although not statistically significant, we observed green phenotypes more frequently in areas with less water on the landscape and in locations closer to tree cover. Burnsi phenotypes were more common in wetlands that did not dry out and Kandiyohi phenotypes were more common in wetlands with aquatic vegetation, although not significantly. No pigment polymorphism was associated with body size. We found no indication of spatial structure, suggesting ample gene flow. The correlations were generally weak, but some were consistent with hypotheses of adaptive benefits. This genetically determined phenotypic variation could be important under changing climactic conditions or if land uses change

Magnetohydrodynamic Simulations of Shock Interactions with Radiative Clouds

We present results from two-dimensional numerical simulations of the interactions between magnetized shocks and radiative clouds. Our primary goal is to characterize the dynamical evolution of the shocked clouds. We perform runs in both the strong and weak magnetic field limits and consider three different field orientations. For the geometries considered, we generally find that magnetic fields external to, but concentrated near, the surface of the cloud suppress the growth of destructive hydrodynamic instabilities. External fields also increase the compression of the cloud by effectively acting as a confinement mechanism driven by the interstellar flow and local field stretching. This can have a dramatic effect on both the efficiency of radiative cooling, which tends to increase with increasing magnetic field strength, and on the size and distribution of condensed cooled fragments. In contrast, fields acting predominately internally to the cloud tend to resist compression, thereby inhibiting cooling. We observe that, even at modest strengths ({beta}{sub o} {approx}< 100), internal fields can completely suppress low-temperature (T < 100 K) cooling

Magnetohydrodynamic Simulations of Shock Interactions with Radiative Clouds

We present results from two-dimensional numerical simulations of the interactions between magnetized shocks and radiative clouds. Our primary goal is to characterize the dynamical evolution of the shocked clouds. We perform runs in both the strong and weak magnetic field limits and consider three different field orientations. For the geometries considered, we generally find that magnetic fields external to, but concentrated near, the surface of the cloud suppress the growth of destructive hydrodynamic instabilities. External fields also increase the compression of the cloud by effectively acting as a confinement mechanism driven by the interstellar flow and local field stretching. This can have a dramatic effect on both the efficiency of radiative cooling, which tends to increase with increasing magnetic field strength, and on the size and distribution of condensed cooled fragments. In contrast, fields acting predominately internally to the cloud tend to resist compression, thereby inhibiting cooling. We observe that, even at modest strengths, internal fields can completely suppress low-temperature cooling.Comment: 21 pages, 9 figures, to appear in The Astrophysical Journa

Measurement of Longitudinal Spin Transfer to Lambda Hyperons in Deep-Inelastic Lepton Scattering

Spin transfer in deep-inelastic Lambda electroproduction has been studied with the HERMES detector using the 27.6 GeV polarized positron beam in the HERA storage ring. For an average fractional energy transfer = 0.45, the longitudinal spin transfer from the virtual photon to the Lambda has been extracted. The spin transfer along the Lambda momentum direction is found to be 0.11 +/- 0.17 (stat) +/- 0.03 (sys); similar values are found for other possible choices for the longitudinal spin direction of the Lambda. This result is the most precise value obtained to date from deep-inelastic scattering with charged lepton beams, and is sensitive to polarized up quark fragmentation to hyperon states. The experimental result is found to be in general agreement with various models of the Lambda spin content, and is consistent with the assumption of helicity conservation in the fragmentation process.Comment: 8 pages, 3 figures; new version has an expanded discussion and small format change

Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns.

The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs-locomotor bouts-matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior

Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice

BackgroundEvery bout of exercise mobilizes and redistributes large numbers of effector lymphocytes with a cytotoxic and tissue migration phenotype. The frequent redistribution of these cells is purported to increase immune surveillance and play a mechanistic role in reducing cancer risk and slowing tumor progression in physically active cancer survivors. Our aim was to provide the first detailed single cell transcriptomic analysis of exercise-mobilized lymphocytes and test their effectiveness as a donor lymphocyte infusion (DLI) in xenogeneic mice engrafted with human leukemia.MethodsPeripheral blood mononuclear cells (PBMCs) were collected from healthy volunteers at rest and at the end of an acute bout of cycling exercise. Flow cytometry and single-cell RNA sequencing was performed to identify phenotypic and transcriptomic differences between resting and exercise-mobilized cells using a targeted gene expression panel curated for human immunology. PBMCs were injected into the tail vein of xenogeneic NSG-IL-15 mice and subsequently challenged with a luciferase tagged chronic myelogenous leukemia cell line (K562). Tumor growth (bioluminescence) and xenogeneic graft-versus-host disease (GvHD) were monitored bi-weekly for 40-days.ResultsExercise preferentially mobilized NK-cell, CD8+ T-cell and monocyte subtypes with a differentiated and effector phenotype, without significantly mobilizing CD4+ regulatory T-cells. Mobilized effector lymphocytes, particularly effector-memory CD8+ T-cells and NK-cells, displayed differentially expressed genes and enriched gene sets associated with anti-tumor activity, including cytotoxicity, migration/chemotaxis, antigen binding, cytokine responsiveness and alloreactivity (e.g. graft-versus-host/leukemia). Mice receiving exercise-mobilized PBMCs had lower tumor burden and higher overall survival (4.14E+08 photons/s and 47%, respectively) at day 40 compared to mice receiving resting PBMCs (12.1E+08 photons/s and 22%, respectively) from the same donors (p<0.05). Human immune cell engraftment was similar for resting and exercise-mobilized DLI. However, when compared to non-tumor bearing mice, K562 increased the expansion of NK-cell and CD3+/CD4-/CD8- T-cells in mice receiving exercise-mobilized but not resting lymphocytes, 1-2 weeks after DLI. No differences in GvHD or GvHD-free survival was observed between groups either with or without K562 challenge.ConclusionExercise in humans mobilizes effector lymphocytes with an anti-tumor transcriptomic profile and their use as DLI extends survival and enhances the graft-versus-leukemia (GvL) effect without exacerbating GvHD in human leukemia bearing xenogeneic mice. Exercise may serve as an effective and economical adjuvant to increase the GvL effects of allogeneic cell therapies without intensifying GvHD

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival