Local and cross‐seasonal associations of climate and land use with abundance of monarch butterflies Danaus plexippus

Quantifying how climate and land use factors drive population dynamics at regional scales is complex because it depends on the extent of spatial and temporal synchrony among local populations, and the integration of population processes throughout a species’ annual cycle. We modeled weekly, site‐specific summer abundance (1994–2013) of monarch butterflies Danaus plexippus at sites across Illinois, USA to assess relative associations of monarch abundance with climate and land use variables during the winter, spring, and summer stages of their annual cycle. We developed negative binomial regression models to estimate monarch abundance during recruitment in Illinois as a function of local climate, site‐specific crop cover, and county‐level herbicide (glyphosate) application. We also incorporated cross‐seasonal covariates, including annual abundance of wintering monarchs in Mexico and climate conditions during spring migration and breeding in Texas, USA. We provide the first empirical evidence of a negative association between county‐level glyphosate application and local abundance of adult monarchs, particularly in areas of concentrated agriculture. However, this association was only evident during the initial years of the adoption of herbicide‐resistant crops (1994–2003). We also found that wetter and, to a lesser degree, cooler springs in Texas were associated with higher summer abundances in Illinois, as were relatively cool local summer temperatures in Illinois. Site‐specific abundance of monarchs averaged approximately one fewer per site from 2004–2013 than during the previous decade, suggesting a recent decline in local abundance of monarch butterflies on their summer breeding grounds in Illinois. Our results demonstrate that seasonal climate and land use are associated with trends in adult monarch abundance, and our approach highlights the value of considering fine‐resolution temporal fluctuations in population‐level responses to environmental conditions when inferring the dynamics of migratory species.     

Histamine selectively interrupts VE-cadherin adhesion independently of capacitive calcium entry

Histamine is an important agent of innate immunity, transiently increasing the flux of immune-competent molecules from the vascular space to the tissues and then allowing rapid restoration of the integrity of the endothelial barrier. In previous work we found that histamine alters the endothelial barrier by disrupting cell-cell adhesion and identified VE-cadherin as an essential participant in this process. The previous work did not determine whether histamine directly interrupted VE-cadherin adhesion, whether the effects of histamine were selective for cadherin adhesion, or whether capacitive calcium flux across the cell membrane was necessary for the effects of histamine on cell-cell adhesion. In the current work we found that histamine directly interrupts adhesion of L cells expressing the type 1 histamine (H1) receptor and VE-cadherin to a VE-cadherin-Fc fusion protein. In contrast, integrin-mediated adhesion to fibronectin of the same L cells expressing the H1 receptor was not affected by histamine, demonstrating that the effects of histamine are selective for cadherin adhesion. Some of the effects of many edemagenic agonists on endothelium are dependent on the capacitive flux of calcium across the endothelial cell membrane. Blocking capacitive calcium flux with LaCl3 did not prevent histamine from interrupting VE-cadherin adhesion of transfected L cells, nor did it prevent histamine from interrupting cell-cell adhesion of human umbilical vein endothelial cells. These data support the contentions that histamine directly and selectively interrupts cadherin adhesion and this effect on cadherin adhesion is independent of capacitive calcium flux.     

Amyloidosis: a model of misfolded protein disorder

Amyloidosis bears many characteristics of orphan diseases. Its diagnosis is difficult and often delayed. The main reasons thereof are its quite various clinical presentation: amyloidosis behaves as a new great masquerader, and the need to get a tissue sample to submit to specific dyes. Although we have been able for a long time to recognize amyloid, its intimate nature has remained quite completely enigmatic until recently. In fact, major advances in this way have appeared only in the last decade and it is now possible to consider the mechanisms of amyloidosis as a multistep phenomenon. Amyloidosis is no more thought only as a < storage disease > of the extracellular space. This archaic viewpoint has shifted to the emerging paradigm of misfolded protein disorders. Amyloid proteins thus appear as a subgroup of misfolded proteins, where misfolding leads to subsequent aggregation. This aggregation may be a generic property of polypeptide chains possibly linked to their common peptide backbone that does not depend on specific amino acid sequences. And, in fact, many proteins can in vitro form amyloid-like aggregates, while in vivo, only 20 amyloid proteins have been so far identified. Although misfolding and aggregation are quite well studied in vitro, the last step of amyloid deposition, i.e. anchorage to the extracellular matrix, can not be so easily approached. Proteoglycans and serum amyloid P component have nevertheless been identified as key elements involved in extracellular deposition of amyloid proteins. These advances have opened new avenues in the therapeutic of amyloid disorders. Current treatment consists of support or replacement of impaired organ function and measures to reduce the production of amyloidogenic precursor proteins. Potential novel therapeutic strategies include stabilisation of the native fold of precursor proteins with targeted small molecules, reversion of misfolded proteins to their native state with < beta-sheet breakers >, inhibition of amyloid fibril propagation and enhancement of amyloid clearance either through immunotherapy or by reducing the stability of deposits through depletion of serum amyloid P component, and breaking the anchorage to the extracellular matrix with glycosaminoglycan analogs.     

The Three-dimensional structure of a superantigen-like protein,SET3, from a pathogenicity island of the Staphylococcus aureus genome

The staphylococcal enterotoxin-like toxins (SETs) are a family of proteins encoded within the Staphylococcus aureus genome that were identified by their similarity to the well described bacterial superantigens. The first crystal structure of a member of the SET family, SET3, has been determined to 1.9 A (R = 0.205, R(free) = 0.240) and reveals a fold characteristic of the superantigen family but with significant differences. The SET proteins are secreted at varying levels by staphylococcal isolates, and seroconversion studies of normal individuals indicate that they are strongly antigenic to humans. Recombinant SETs do not exhibit any of the properties expected of superantigens such as major histocompatibility complex class II binding or broad T-cell activation, suggesting they have an entirely different function. The fact that the whole gene family is clustered within the pathogenicity island SaIn2 of the S. aureus genome suggests that they are involved in host/pathogen interactions.     

Mapping of quantitative trait loci for canopy-wilting trait in soybean (Glycine max L. Merr)

Drought stress adversely affects [Glycine max (L.) Merr] soybean at most developmental stages, which collectively results in yield reduction. Little information is available on relative contribution and chromosomal locations of quantitative trait loci (QTL) conditioning drought tolerance in soybean. A Japanese germplasm accession, PI 416937, was found to possess drought resistance. Under moisture-deficit conditions, PI 416937 wilted more slowly in the field than elite cultivars and has been used as a parent in breeding programs to improve soybean productivity. A recombinant inbred line (RIL) population was derived from a cross between PI 416937 and Benning, and the population was phenotyped for canopy wilting under rain-fed field conditions in five distinct environments to identify the QTL associated with the canopy-wilting trait. In a combined analysis over environments, seven QTL that explained 75?% of the variation in canopy-wilting trait were identified on different chromosomes, implying the complexity of this trait. Five QTL inherited their positive alleles from PI 416937. Surprisingly, the other two QTL inherited their positive alleles from Benning. These putative QTL were co-localized with other QTL previously identified as related to plant abiotic stresses in soybean, suggesting that canopy-wilting QTL may be associated with additional morpho-physiological traits in soybean. A locus on chromosome 12 (Gm12) from PI 416937 was detected in the combined analysis as well as in each individual environment, and explained 27?% of the variation in canopy-wilting. QTL identified in PI 416937 could provide an efficient means to augment field-oriented development of drought-tolerant soybean cultivars.     

Total internal reflection fluorescence correlation spectroscopy: effects of lateral diffusion and surface-generated fluorescence

Fluorescence correlation spectroscopy with total internal reflection excitation (TIR-FCS) is a promising method with emerging biological applications for measuring binding dynamics of fluorescent molecules to a planar substrate as well as diffusion coefficients and concentrations at the interface. Models for correlation functions proposed so far are rather approximate for most conditions, since they neglect lateral diffusion of fluorophores. Here we propose accurate extensions of previously published models for axial correlation functions taking into account lateral diffusion through detection profiles realized in typical experiments. In addition, we consider the effects of surface-generated emission in objective-based TIR-FCS. The expressions for correlation functions presented here will facilitate quantitative and accurate measurements with TIR-FCS.     

Butterfly edge effects are predicted by a simple model in a complex landscape

Edge responses have been studied for decades and form a critical component of our understanding of how organisms respond to landscape structure and habitat fragmentation. Until recently, however, the lack of a general, conceptual framework has made it difficult to make sense of the patterns and variability reported in the edge literature. We present a test of an edge effects model which predicts that organisms should avoid edges with less-preferred habitat, show increased abundance near edges with preferred habitat or habitat containing complementary resources, and show no response to edges with similar-quality habitat that offers only supplementary resources. We tested the predictions of this model against observations of the edge responses of 15 butterfly species at 12 different edge types within a complex, desert riparian landscape. Observations matched model predictions more than would be expected by chance for the 211 species/edge combinations tested over 3 years of study. In cases where positive or negative edge responses were predicted, observed responses matched those predictions 70% of the time. While the model tends to underpredict neutral results, it was rare that an observed edge response contradicted that predicted by the model. This study also supported the two primary ecological mechanisms underlying the model, although not equally. We detected a positive relationship between habitat preferences and the slope of the observed edge response, suggesting that this basic life history trait underlies edge effects and influences their magnitude. Empirical evidence also suggested the presence of complementary resources underlies positive edge responses, but only when completely confined to the adjacent habitat. This multi-species test of a general edge effects model at multiple edge types shows that resource-based mechanisms can explain many edge responses and that a modest knowledge of life history attributes and resource availability is sufficient for predicting and understanding many edge responses in complex landscapes. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Chronic immune activation in HIV-1 infection contributes to reduced interferon alpha production via enhanced CD40:CD40 ligand interaction

Although a signature of increased interferon (IFN-)alpha production is observed in HIV-1 infection, the response of circulating plasmacytoid dendritic cells (PDC) to Toll-like receptor ligand stimulation is substantially impaired. This functional PDC deficit, which we specifically observed in HIV-1 infected individuals with less than 500 CD4+ T cells/µl, is not well understood. We provide evidence that the peripheral IFN-alpha production in HIV-1 infection is actively suppressed by the enhanced interaction of CD40 ligand (CD40L), a member of the tumor necrosis factor family, and its receptor CD40, which are both upregulated upon immune activation. Plasma levels of soluble CD40L were significantly higher in untreated HIV-1 infected individuals (n = 52) than in subjects on long-term antiretroviral therapy (n = 62, p<0.03) and in uninfected control donors (n = 16, p<0.001). Concomitantly, cell-associated CD40L and the expression of the receptor CD40 on the PDC were significantly upregulated in HIV-1 infection (p<0.05). Soluble and cell-associated CD40L inhibited the PDC-derived IFN-alpha production by CpG oligodeoxynucleotides dose-dependently. This suppressive effect was observed at much lower, physiological CD40L concentrations in peripheral blood mononuclear cells (PBMC) of HIV-1 infected individuals compared to controls (p<0.05). The CpG-induced IFN-alpha production in PBMC of HIV-1 infected donors was directly correlated with PDC and CD4+ T cell counts, and inversely correlated with the viral loads (p<0.001). In HIV-1 infected donors with less than 500 CD4+ T cells/µl, the CpG-induced IFN-alpha production was significantly correlated with the percentage of CD40-expressing PDC and the level of CD40 expression on these cells (p<0.05), whereas CD40L plasma levels played a minor role. In addition, low-dose CD40L contributed to the enhanced production of interleukin 6 and 8 in PBMC of HIV-1 infected donors compared to controls. Our data support the conclusion that the chronic immune activation in HIV-1 infection impairs peripheral PDC innate immune responses at least in part via enhanced CD40:CD40L interactions.     

Allosteric antibody inhibition of human hepsin protease

Hepsin is a type II transmembrane serine protease that is expressed in several human tissues. Overexpression of hepsin has been found to correlate with tumour progression and metastasis, which is so far best studied for prostate cancer, where more than 90% of such tumours show this characteristic. To enable improved future patient treatment, we have developed a monoclonal humanized antibody that selectively inhibits human hepsin and does not inhibit other related proteases. We found that our antibody, hH35, potently inhibits hepsin enzymatic activity at nanomolar concentrations. Kinetic characterization revealed non-linear, slow, tight-binding inhibition. This correlates with the crystal structure we obtained for the human hepsin-hH35 antibody Fab fragment complex, which showed that the antibody binds hepsin around α3-helix, located far from the active centre. The unique allosteric mode of inhibition of hH35 is distinct from the recently described HGFA (hepatocyte growth factor activator) allosteric antibody inhibition. We further explain how a small change in the antibody design induces dramatic structural rearrangements in the hepsin antigen upon binding, leading to complete enzyme inactivation.