Bateman Gradients and Alternative Mating Strategies in a Marine Isopod

The “Bateman gradient” provides a means for estimating the strength of sexual selection. Although widely used for this purpose, this approach has not been applied to examine the covariance between mate numbers and offspring numbers among alternative mating strategies. Differences in this covariance could exist if the average fitnesses of different mating phenotypes were unequal, as has been suggested for “alternative mating tactics.” We tested this hypothesis in Paracerceis sculpta, a sexually dimorphic marine isopod in which three male morphs coexist. We found no significant differences in sexual competency and no significant differences in Bateman gradients among morphs, that is, the average morph fitnesses were equivalent. However, with data pooled among morphs, we found a significant sex difference in Bateman gradients, as expected for dimorphic species; females gained no additional fitness from mating with multiple males, whereas male fitness increased with increasing mate numbers. In nature, the fitnesses of the three morphs are variable due to differences in the availability of receptive females. Our results suggest that differences in mate availability, not differences in sexual competency, are responsible for observed variance in fitness within, and for the equality of fitnesses among, the three male morphs in this species

Alternative Mating Tactics in Socially Monogamous Prairie Voles, Microtus ochrogaster

Alternative mating tactics appear to evolve when sexual selection is strong. Because such conditions are usually observed in species with polygynous or polyandrous mating systems, alternative mating tactics in monogamous mating systems are seldom documented and are poorly understood. In prairie voles, Microtus ochrogaster, a species widely known for forming monogamous pair-bonds, the expression of territoriality within each sex is dimorphic, and includes non-territorial “wanderers” as well as territorial “residents.” To explore the variance in fitness, measured in offspring numbers, among breeding individuals expressing these alternative mating tactics, we compiled parentage data over 3 years for male and female prairie voles from natural populations in Indiana and Kansas, USA. We found that: (1) the average fitnesses of males and females within each population were identical when adjusted by the sex ratio; (2) the variance in fitness in male and female prairie voles was comparable to that of highly polygynous species; (3) The average fitnesses of male tactics, and of female tactics, were equivalent within and among years within each location; (4) consistent with negative frequency-dependent selection acting on mating phenotypes, the between-tactic variance in fitness for male and female mating tactics decreased with increasing study duration; (5) consistent with negative assortative mating, resident males, and wanderer females produced offspring primarily in monogamous partnerships, whereas wanderer males and resident females produced offspring primarily in polygamous partnerships. Our results show that the conditions necessary for the persistence of alternative mating tactics are indistinguishable from those for phenotypically less flexible alternative mating strategies, and that alternative mating tactics can evolve in both sexes in monogamous species when fitness variance within each sex is large

A Comparison of Genetic Variation in Two Endemic Thermal Spring Isopods, <em>Thermosphaeroma thermophilum</em> and <em>T. milleri</em> (Crustacea - Isopoda: Sphaeromatidae)

Populations with reduced gene flow and restricted population size are expected to show reduced genetic variation. Using starch gel electrophoresis, we examined allozyme variation at 12 loci in two species of freshwater, sphaeromatid isopods. Thermosphaeroma thermophilum, an endangered species, inhabits a single thermal spring in central New Mexico, USA; and T. milleri, inhabits a more complex thermal spring system in northern Chihuahua, México. We found no significant differences in allelic variation between the sexes within each species. Between species, electromorphs at each locus differed significantly in both number and moiety on the gel, with T. milleri showing greater polymorphism and greater heterozygosity than T. thermophilum. Nei’s unbiased genetic distance, calculated using the nine loci common to both populations (D = 0.75), was consistent with morphological classification of T. thermophilum and T. milleri as separate species, as well as with molecular analyses suggesting that these populations have been separated since the late Cretaceous (88 myr). Moreover, consistent with the theoretical expectation that small, isolated populations will exhibit reduced genetic variation, T. thermophilum, an endangered species, exhibited significantly less genetic variation than the more numerous and less confined T. milleri. We compare our results with other recent studies using this approach to understand the population genetics of natural populations

Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "super responders" (24-month C-peptide ≥ baseline), and "nonresponders" (12-month C-peptide &lt; baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4+ T cells and CD4+/CD8+ T-cell ratio and increased CD16+CD56hi natural killer cells (NK), CD4+ effector memory T cells (Tem), CD4+PD-1+ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3+Helios+ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G-CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G-CSF as a prevention strategy in high-risk subjects

UIML: an appliance-independent xml user interface language

Abstract Today&apos;s Internet appliances feature user interface technologies almost unknown a few years ago: touch screens, styli, handwriting and voice recognition, speech synthesis, tiny screens, and more. This richness creates problems. First, different appliances use different languages: WML for cell phones; SpeechML, JSML, and VoxML for voice enabled devices such as phones; HTML and XUL for desktop computers, and so on. Thus, developers must maintain multiple source code families to deploy interfaces to one information system on multiple appliances. Second, user interfaces differ dramatically in complexity (e.g, PC versus cell phone interfaces). Thus, developers must also manage interface content. Third, developers risk writing appliance-specific interfaces for an appliance that might not be on the market tomorrow. A solution is to build interfaces with a single, universal language free of assumptions about appliances and interface technology. This paper introduces such a language, the User Interface Markup Language (UIML), an XML-compliant language. UIML insulates the interface designer from the peculiarities of different appliances through style sheets. A measure of the power of UIML is that it can replace hand-coding of Java AWT or Swing user interfaces

MMS observations of storm‐time magnetopause boundary layers in the vicinity of the Southern cusp

80MSFC20C0019 - NASAPublished versio

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