Predictive Value of Species Sensitivity Distributions for Effects of Herbicides in Freshwater Ecosystems

In this article we present a review of the laboratory and field toxicity of herbicides to aquatic ecosystems. Single-species acute toxicity data and (micro)mesocosm data were collated for nine herbicides. These data were used to investigate the importance of test species selection in constructing species sensitivity distributions (SSDs), and in estimating hazardous concentrations (i.e., HC5) protective for freshwater aquatic ecosystems. A lognormal model was fitted to toxicity data (acute EC50s and chronic NOECs) and the resulting distribution used to estimate lower (95% confidence), median (50% confidence), and upper (5% confidence), HC5 values. The taxonomic composition of the species assemblage used to construct the SSD does have a significant influence on the assessment of hazard and only sensitive primary producers should be included for the risk assessment of herbicides. No systematic difference in sensitivity between standard and non-standard test species was observed. Hazardous concentrations estimated using laboratory-derived acute and chronic toxicity data for sensitive freshwater primary producers were compared to the response of herbicide-stressed freshwater ecosystems using a similar exposure regime. The lower limit of the acute HC5 and the median value of the chronic HC5 were protective of adverse effects in aquatic micro/mesocosms even under a long-term exposure regime. The median HC5 estimate based on acute data was protective of adverse ecological effects in freshwater ecosystems when a pulsed or short-term exposure regime was used in the microcosm and mesocosm experiments. There was also concordance between the predictions from the effect model PERPEST and the concentrations at which clear effects started to emerge in laboratory and field studies. However, compared to the SSD concept, the PERPEST model is able to provide more information on ecological risks when a common toxicological mode of action is evaluated as it considers both recovery and indirect effects.     

Scope for growth in Gammarus pulex,a freshwater benthic detritivore

Although toxic substances affect the physiological processes of individual organisms, their ecological impacts occur at the population and community levels. However, physiological processes can often be assessed more easily and precisely than population and community ones. Here we argue that scope for growth, the difference between the energy input to an organism from its food and the output from respiratory metabolism, can give a good physiological measure of stress that, at least in principle, is straightforwardly related to population and community processes. We describe, in detail, how scope for growth can be measured in Gammarus pulex (Crustacea, Amphipoda). The results indicate that both zinc and low pH can significantly reduce the scope for growth of individuals and that the most sensitive component of the energy budget is food absorption.     

A novel retinoid-response gene set in vascular smooth muscle cells

A modified suppression subtractive hybridization assay was performed to uncover genes induced by all-trans retinoic acid in cultured smooth muscle cells (SMC). Northern blotting studies confirmed the induction of 14 genes, many of which have heretofore been unrecognized as retinoid-inducible. Temporal expression and cycloheximide studies allowed us to categorize these genes as either immediate-early (LOX-1, endolyn, Stoned B/TFIIA alpha/beta-like factor, Src Suppressed C Kinase Substrate, and tissue transglutaminase) or delayed (cathepsin-L, ceruloplasmin, epithelin, importin alpha, alpha(8)-integrin, lactate dehydrogenase B, retinol dehydrogenase, spermidine/spermine N(1)-acetyltransferase, and VCAM-1) retinoid-response genes. A survey of rat tissues showed two of the genes (tissue transglutaminase and alpha(8)-integrin) to be highly restricted to vascular tissue. In situ hybridization verified expression of both tissue transglutaminase and alpha(8)-integrin to SMC in balloon-injured rat carotid artery. These findings unveil a new retinoid-response gene set that should be exploited to define molecular pathways involved in the antagonistic effects of retinoids on SMC growth and neointimal formation.     

Use of a Monoclonal Antibody-Based Immunoassay for the Detection and Quantification of Heliscus lugdunensis Colonizing Alder Leaves and Roots

A genus-specific monoclonal antibody, NG-CF10, raised in a previous study to the fungal pathogen Nectria galligena, was found to recognize the aquatic hyphomycete Heliscus lugdunensis (anamorph) and its teleomorph Nectria lugdunensis. Using this MAb in a plate trapped antigen- ELISA we could detect and determine the biomass of Heliscus lugdunensis in mixed assemblages in both naturally occurring and artificially inoculated leaves and roots of Alnus glutinosa trees. Initial studies indicate that the biomass associated with naturally occurring leaf material is significantly lower than that recorded with laboratory inoculated leaves, suggesting that biomass production is limited in the natural environment. Significantly lower biomass was associated with roots when compared with leaf material, which supports the proposition that rather than a major substrate for the growth of aquatic hyphomycetes, roots act as a refugium for fungal growth.     

Mast cells in tumor growth: Angiogenesis,tissue remodelling and immune-modulation

There is a growing acceptance that tumor-infiltrating myeloid cells play an active role in tumor growth and mast cells are one of the earliest cell types to infiltrate developing tumors. Mast cells accumulate at the boundary between healthy tissues and malignancies and are often found in close association with blood vessels within the tumor microenvironment. They express many pro-angiogenic compounds, and may play an early role in angiogenesis within developing tumors. Mast cells also remodel extracellular matrix during wound healing, and this function is subverted in tumor growth, promoting tumor spread and metastasis. In addition, mast cells modulate immune responses by dampening immune rejection or directing immune cell recruitment, depending on local stimuli. In this review, we focus on key roles for mast cells in angiogenesis, tissue remodelling and immune modulation and highlight recent findings on the integral role that mast cells play in tumor growth. New findings suggest that mast cells may serve as a novel therapeutic target for cancer treatment and that inhibiting mast cell function may lead to tumor regression.     

Periodic ultraviolet-C illumination for marine sensor antifouling

Ultraviolet light has intriguing potential as a marine antifoulant, targeting almost any species and applicable to almost any surface, while not accumulating in the environment. This study field-tested the effects of periodic ultraviolet-C illumination on marine macrofouling. Across four experiments, several UV illumination duty cycles were tested against controls with no illumination. Duty cycles between 1:2 (time with UV:total time per cycle) and 1:20 were all similarly effective, inhibiting almost all macrofouling at three different temperate Northeast Pacific and Northwest Atlantic sites. Susceptible taxa included barnacles, bryozoans, tunicates (colonial and solitary), and, to a slightly lesser extent, mussels. Duty cycles of 1:30 and 1:60 reduced but did not eliminate biofouling. Measurements of ultraviolet illumination on oceanographic sensors showed similar results. The results suggest further investigation of ultraviolet light as an antifoulant for marine sensors, including susceptibility of other taxa, optimizing illumination patterns, and exploring the potential for evolved resistance.     

Dendritic iodinated contrast agents with PEG-cores for CT imaging: synthesis and preliminary characterization

The purpose of this study was to design, synthesize, and initially characterize a representative set of novel constructs for large-molecular radiographic/computed tomography (CT) contrast agents, intended for a primarily intravascular distribution. A new assembly of well-known and biocompatible components consists of paired, symmetrical dendritic polylysines initiated from both ends of a poly(ethylene glycol) (PEG) core, yielding an array of multiple free amino groups to which were conjugated highly soluble and stable triiodophthalamide ("triiodo") moieties. An array of six dendritic contrast agents was synthesized originally, using three different PEG cores (3, 6, 12 kDa) with t-Boc lysine-generated dendrimer "amplifiers" (from three to five generations) containing 16 to 64 amino groups for conjugation with reactive triiodo moieties. A clinically used, nonionic, small molecular CT contrast agent, iobitridol, was derivatized via a hydroxyl protection/deprotection strategy, introducing a new carboxyl group available for conjugation to the lysine amino groups of dendrimers. Final products were purified by size exclusion chromatography and characterized by NMR, UV, HPLC, and elemental analysis. Preliminary evaluations were conducted for physicochemical characterization and in vivo CT contrast enhancement in a rat model. All six iodinated PEG-core dendrimer conjugates were synthesized in good yields, with a high degree of size monodispersity, large apparent molecular weight, favored physicochemical properties. A representative compound, PEG12000-carbamate-Gen4-IOB conjugate, 27% (w%) rich in iodine, demonstrated a desirable strong and persistent intravascular enhancement with a monoexponential blood half-life of approximately 35 min assayed by dynamic CT imaging and also showed high water solubility (>550 mg/mL at 25 degrees C), large apparent molecular size (comparable to a 143-kDa protein), high hydrophilicity (butanol-water partition coefficient 0.015), and stability to autoclaving conditions. This study showed the synthetic feasibility, desired basic characteristics, and potential utility for CT contrast enhancement achieved with a new type of iodinated, large-molecular PEG-core dendritic construct. Further development of this class of macromolecular contrast agents will be required to define the optimal formulation, pharmacology, safety profile, and the full range of diagnostic applications including tumor microvascular quantitative characterization by CT imaging.     

Identification and developmental expression analysis of a novel homeobox gene closely linked to the mouse Twirler mutation

The Twirler mutation arose spontaneously and causes inner ear defects in heterozygous and cleft lip and/or cleft palate in homozygous mutant mice, providing a unique animal model for investigating the molecular mechanisms of inner ear and craniofacial development. Here, we report the identification of a novel homeobox gene, Iroquois-related homeobox like-1 (Irxl1), from the Twirler locus. Irxl1 encodes a TALE-family homeodomain protein with its homeodomain exhibiting the highest amino acid sequence identity (54%) to those of invertebrate Iroquois and vertebrate Irx subfamily members. The putative Irxl1 protein lacks the Iro-box, a conserved motif in all known members of the Irx subfamily. Searching the databases showed that Irxl1 orthologs exist in Xenopus, chick, and mammals. In situ hybridization analyses of mouse embryos at various developmental stages showed that Irxl1 mRNA is highly expressed in the frontonasal process and palatal mesenchyme during primary and secondary palate development. In addition, Irxl1 mRNA is strongly expressed in mesenchyme surrounding the developing inner ear, in discrete regions of the developing mandible, in the dermamyotome during somite differentiation, and in a subset of muscular structures in late embryonic stages. The developmental expression pattern indicates that Irxl1 is a good candidate gene for the Twirler gene.