Lambda and Antilambda polarization from deep inelastic muon scattering

We report results of the first measurements of Lambda and Antilambda polarization produced in deep inelastic polarized muon scattering on the nucleon. The results are consistent with an expected trend towards positive polarization with increasing x_F. The polarizations of Lambda and Antilambda appear to have opposite signs. A large negative polarization for Lambda at low positive x_F is observed and is not explained by existing models.A possible interpretation is presented.Comment: 9 pages, 2 figure

Combining Antigen-Based Therapy with GABA Treatment Synergistically Prolongs Survival of Transplanted ß-Cells in Diabetic NOD Mice

Antigen-based therapies (ABTs) very effectively prevent the development of type 1 diabetes (T1D) when given to young nonobese diabetic (NOD) mice, however, they have little or no ability to reverse hyperglycemia in newly diabetic NOD mice. More importantly, ABTs have not yet demonstrated an ability to effectively preserve residual ß-cells in individuals newly diagnosed with type 1 diabetes (T1D). Accordingly, there is great interest in identifying new treatments that can be combined with ABTs to safely protect ß-cells in diabetic animals. The activation of γ-aminobutyric acid (GABA) receptors (GABA-Rs) on immune cells has been shown to prevent T1D, experimental autoimmune encephalomyelitis (EAE) and rheumatoid arthritis in mouse models. Based on GABA's ability to inhibit different autoimmune diseases and its safety profile, we tested whether the combination of ABT with GABA treatment could prolong the survival of transplanted ß-cells in newly diabetic NOD mice. Newly diabetic NOD mice were untreated, or given GAD/alum (20 or 100 µg) and placed on plain drinking water, or water containing GABA (2 or 6 mg/ml). Twenty-eight days later, they received syngenic pancreas grafts and were monitored for the recurrence of hyperglycemia. Hyperglycemia reoccurred in the recipients given plain water, GAD monotherapy, GABA monotherapy, GAD (20 µg)+GABA (2 mg/ml), GAD (20 µg)+GABA (6 mg/ml) and GAD (100 µg)+GABA (6 mg/ml) about 1, 2-3, 3, 2-3, 3-8 and 10-11 weeks post-transplantation, respectively. Thus, combined GABA and ABT treatment had a synergistic effect in a dose-dependent fashion. These findings suggest that co-treatment with GABA (or other GABA-R agonists) may provide a new strategy to safely enhance the efficacy of other therapeutics designed to prevent or reverse T1D, as well as other T cell-mediated autoimmune diseases

Two Lysines in the Forkhead Domain of Foxp3 Are Key to T Regulatory Cell Function

Background: The forkhead box transcription factor, Foxp3, is master regulator of the development and function of CD4+CD25+ T regulatory (Treg) cells that limit autoimmunity and maintain immune homeostasis. The carboxyl-terminal forkhead (FKH) domain is required for the nuclear localization and DNA binding of Foxp3. We assessed how individual FKH lysines contribute to the functions of Foxp3 in Treg cells. Methodology/Principal Findings: We found that mutation of FKH lysines at position 382 (K17) and at position 393 (K18) impaired Foxp3 DNA binding and inhibited Treg suppressive function in vivo and in vitro. These lysine mutations did not affect the level of expression of Foxp3 but inhibited IL-2 promoter remodeling and had important and differing effects on Treg-associated gene expression. Conclusions/Significance: These data point to complex effects of post-translational modifications at individual lysines within the Foxp3 FKH domain that affect Treg function. Modulation of these events using small molecule inhibitors ma

Double trouble at high density::Cross-level test of ressource-related adaptive plasticity and crowding-related fitness.

Population size is often regulated by negative feedback between population density and individual fitness. At high population densities, animals run into double trouble: they might concurrently suffer from overexploitation of resources and also from negative interference among individuals regardless of resource availability, referred to as crowding. Animals are able to adapt to resource shortages by exhibiting a repertoire of life history and physiological plasticities. In addition to resource-related plasticity, crowding might lead to reduced fitness, with consequences for individual life history. We explored how different mechanisms behind resource-related plasticity and crowding-related fitness act independently or together, using the water flea Daphnia magna as a case study. For testing hypotheses related to mechanisms of plasticity and crowding stress across different biological levels, we used an individual-based population model that is based on dynamic energy budget theory. Each of the hypotheses, represented by a sub-model, is based on specific assumptions on how the uptake and allocation of energy are altered under conditions of resource shortage or crowding. For cross-level testing of different hypotheses, we explored how well the sub-models fit individual level data and also how well they predict population dynamics under different conditions of resource availability. Only operating resource-related and crowding-related hypotheses together enabled accurate model predictions of D. magna population dynamics and size structure. Whereas this study showed that various mechanisms might play a role in the negative feedback between population density and individual life history, it also indicated that different density levels might instigate the onset of the different mechanisms. This study provides an example of how the integration of dynamic energy budget theory and individual-based modelling can facilitate the exploration of mechanisms behind the regulation of population size. Such understanding is important for assessment, management and the conservation of populations and thereby biodiversity in ecosystems

Marine Cyanobacteria Compounds with Anticancer Properties: Implication of Apoptosis

Marine cyanobacteria have been proved to be an important source of potential anticancer drugs. Although several compounds were found to be cytotoxic to cancer cells in culture, the pathways by which cells are affected are still poorly elucidated. For some compounds, cancer cell death was attributed to an implication of apoptosis through morphological apoptotic features, implication of caspases and proteins of the Bcl-2 family, and other mechanisms such as interference with microtubules dynamics, cell cycle arrest and inhibition of proteases other than caspases

The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in nonobese diabetic mice at different ages.

The nonobese diabetic (NOD) mouse spontaneously develops several autoimmune diseases, including type 1 diabetes and to a lesser extent thyroiditis and sialitis. Imbalance between effector T cells (Teffs) and regulatory T cells (Tregs) has recently been proposed as a mechanism for the disease pathogenesis in NOD mice, but previous studies have shown the various outcomes by different timing and methods of Treg-depletion. This study was, therefore, designed to compare the consequences of Treg-depletion by the same method (anti-CD25 antibody) on the spectrum of organ-specific autoimmune diseases in NOD mice of different ages. Treg-depletion by anti-CD25 antibody at 10 days of age accelerated development of all three diseases we examined (insulitis/diabetes, thyroiditis, and sialitis); Treg-depletion at 4 weeks of age accelerated only diabetes but not thyroiditis or sialitis; and Treg-depletion at 12 weeks of age hastened only development of thyroiditis and exhibited little influence on diabetes or sialitis. Increased levels of insulin autoantibodies (IAA) were, however, observed in mice depleted of Tregs at 10 days of age, not in those at 4 weeks. Thus, the consequences of Treg-depletion on the spectrum of organ-specific autoimmune diseases depend on the timing of anti-CD25 antibody injection in NOD mice. Aging gradually tips balance between Teffs and Tregs toward Teff-dominance for diabetes, but this balance for thyroiditis and sialitis likely alters more intricately. Our data also suggest that the levels of IAA are not necessarily correlated with diabetes development

Mammalian sex determination—insights from humans and mice

Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models