Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus

Increased levels of B lymphocyte stimulator (BLyS) are associated with systemic autoimmunity in animal models of spontaneous autoimmune disease, and transgenic animals expressing BLyS develop typical autoimmune disease. Here, we demonstrate significant elevations of BLyS in the patients with systemic lupus erythematosus (SLE). The BLyS isolated from the sera of SLE patients had the same m.w. as the natural soluble form and was able to stimulate B cell activation in vitro. Increased BLyS in SLE patients was partially associated with higher levels of anti-dsDNA Ab of the IgG, IgM, and IgA classes, but not associated with the disease activity. Our results suggest that BLyS may be a useful marker for early activation of an autoimmune diathesis and likely plays a critical role in triggering activation of self-Ag-driven autoimmune B cells in human SLE. BLyS may provide an effective therapeutic target in systemic autoimmunity.     

Multimodal Floral Signals and Moth Foraging Decisions

Background

Combinations of floral traits – which operate as attractive signals to pollinators – act on multiple sensory modalities. For Manduca sexta hawkmoths, how learning modifies foraging decisions in response to those traits remains untested, and the contribution of visual and olfactory floral displays on behavior remains unclear.

Methodology/Principal Findings

Using M. sexta and the floral traits of two important nectar resources in southwestern USA, Datura wrightii and Agave palmeri, we examined the relative importance of olfactory and visual signals. Natural visual and olfactory cues from D. wrightii and A. palmeri flowers permits testing the cues at their native intensities and composition – a contrast to many studies that have used artificial stimuli (essential oils, single odorants) that are less ecologically relevant. Results from a series of two-choice assays where the olfactory and visual floral displays were manipulated showed that naïve hawkmoths preferred flowers displaying both olfactory and visual cues. Furthermore, experiments using A. palmeri flowers – a species that is not very attractive to hawkmoths – showed that the visual and olfactory displays did not have synergistic effects. The combination of olfactory and visual display of D. wrightii, however – a flower that is highly attractive to naïve hawkmoths – did influence the time moths spent feeding from the flowers. The importance of the olfactory and visual signals were further demonstrated in learning experiments in which experienced moths, when exposed to uncoupled floral displays, ultimately chose flowers based on the previously experienced olfactory, and not visual, signals. These moths, however, had significantly longer decision times than moths exposed to coupled floral displays.

Conclusions/Significance

These results highlight the importance of specific sensory modalities for foraging hawkmoths while also suggesting that they learn the floral displays as combinatorial signals and use the integrated floral traits from their memory traces to mediate future foraging decisions.     

Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse

Uterine receptivity implies a dialogue between the hormonally primed maternal endometrium and the free-floating blastocyst. Endometrial stromal cells proliferate, avert apoptosis, and undergo decidualization in preparation for implantation; however, the molecular mechanisms that underlie differentiation into the decidual phenotype remain largely undefined. The Notch family of transmembrane receptors transduce extracellular signals responsible for cell survival, cell-to-cell communication, and differentiation, all fundamental processes for decidualization and pregnancy. Using a murine artificial decidualization model, pharmacological inhibition of Notch signaling by γ-secretase inhibition resulted in a significantly decreased deciduoma. Furthermore, a progesterone receptor (PR)-Cre Notch1 bigenic (Notch1(d/d)) confirmed a Notch1-dependent hypomorphic decidual phenotype. Microarray and pathway analysis, following Notch1 ablation, demonstrated significantly altered signaling repertoire. Concomitantly, hierarchical clustering demonstrated Notch1-dependent differences in gene expression. Uteri deprived of Notch1 signaling demonstrated decreased cellular proliferation; namely, reduced proliferation-specific antigen, Ki67, altered p21, cdk6, and cyclinD activity and an increased apoptotic-profile, cleaved caspase-3, Bad, and attenuated Bcl2. The results demonstrate that the preimplantation uterus relies on Notch signaling to inhibit apoptosis of stromal fibroblasts and regulate cell cycle progression, which together promotes successful decidualization. In summary, Notch1 signaling modulates multiple signaling mechanisms crucial for decidualization and these studies provide additional perspectives to the coordination of multiple signaling modalities required during decidualization.     

Research on arbuscular mycorrhizae in Mexico: an historical synthesis and future prospects

This review analyzes the historical development and advances of the research on arbuscular mycorrhizal fungi (AMF) in Mexico, as well as the prospects for future research. AMF-research has been focused on studying both diversity and functionality in several ecosystems of Mexico, but mainly in the tropical dry and rainy ecosystems, and the agricultural systems. In Mexico, 95 species of AMF have been recorded, representing 41% of the known species worldwide. The functional effects of AMF colonization have been examined in approximately 10% of the known host plants, but greenhouse studies continue to dominate over those conducted under field conditions. Even though research to date has been at the organismic level, further effort is needed due to the high plant diversity in Mexico. Studies on AMF biomass under field conditions and more taxonomic determination are required based on morphological features, biochemical determinations (fatty acids) and molecular tools. In addition, ecophysiological and ecological in situ studies would help in understanding the relationships among AMF, soil fauna, nutrients, and host plants. The contribution of AMF to ecosystemic processes is a priority line of research that requires an integrated approach (inter- and multidisciplinary) in order to define the role of AM symbioses for biogeochemical models. The creation of a Mexican mycorrhizal research network has and will help to identify the main challenges. Generating similar research protocols, and sharing databases and experience will assist mycorrhizologists working under the diverse financial and ecological contexts that is to be found in Mexico and Latin America.     

Capillary Filling at the Microscale: Control of Fluid Front Using Geometry

We propose an experimental and theoretical framework for the study of capillary filling at the micro-scale. Our methodology enables us to control the fluid flow regime so that we can characterise properties of Newtonian fluids such as their viscosity. In particular, we study a viscous, non-inertial, non-Washburn regime in which the position of the fluid front increases linearly with time for the whole duration of the experiment. The operating shear-rate range of our apparatus extends over nearly two orders of magnitude. Further, we analyse the advancement of a fluid front within a microcapillary in a system of two immiscible Newtonian liquids. We observe a non-Washburn regime in which the front can accelerate or decelerate depending on the viscosity contrast between the two liquids. We then propose a theoretical model which enables us to study and explain both non-Washburn regimes. Furthermore, our theoretical model allows us to put forward ways to control the emergence of these regimes by means of geometrical parameters of the experimental set-up. Our methodology allows us to design and calibrate a micro-viscosimetre which works at constant pressure.     

T-cell antigen-receptor stoichiometry: pre-clustering for sensitivity

The T-cell antigen receptor (TCR x CD3) is a multi-subunit complex that is responsible for triggering an adaptive immune response. It shows high specificity and sensitivity, while having a low affinity for the ligand. Furthermore, T cells respond to antigen over a wide concentration range. The stoichiometry and architecture of TCR x CD3 in the membrane have been under intense scrutiny because they might be the key to explaining its paradoxical properties. This review highlights new evidence that TCR x CD3 is found on intact unstimulated T cells in a monovalent form (one ligand-binding site per receptor) as well as in several distinct multivalent forms. This is in contrast to the TCR x CD3 stoichiometries determined by several biochemical means; however, these data can be explained by the effects of different detergents on the integrity of the receptor. Here, we discuss a model in which the multivalent receptors are important for the detection of low concentrations of ligand and therefore confer sensitivity, whereas the co-expressed monovalent TCR x CD3s allow a wide dynamic range.