Evidence for acyl homoserine lactone signal production in bacteria associated with marine sponges

We report for the first time the production of acyl homoserine lactones (AHLs) by bacteria associated with marine sponges. Given the involvement of AHLs in bacterial colonization of many higher organisms, we speculate that such quorum sensing signals could play a part in interactions between sponges and the dense bacterial communities living within them.     

Distribution of the invasive New Zealand mudsnail (Potamopyrgus antipodarum) in the Columbia River Estuary and its first recorded occurrence in the diet of juvenile Chinook salmon (Oncorhynchus tshawytscha)

Estuaries play an important role as nurseries and migration corridors for Chinook salmon and other fishes. The invasive New Zealand mudsnail, Potamopyrgus antipodarum (Gray, 1843), has been noted in the Columbia River Estuary and other estuaries in the western USA, yet no studies have addressed the estuarine impacts of this invader. Our data show P. antipodarum is currently found in five peripheral bays and many tributaries of the Columbia River Estuary, where it can constitute a major portion of the benthic invertebrate biomass and where it co-occurs with native amphipod species. We review the history of the P. antipodarum invasion in the Columbia River Estuary and discuss potential impacts on estuarine food webs. We also report the first occurrence of P. antipodarum in the diet of juvenile Chinook salmon from the Columbia River Estuary. Although present in Chinook diets at very low frequencies, our observations of P. antipodarum in Chinook gut contents may represent early stages of food web change due to the establishment of dense estuarine snail populations. Additional research is needed to determine the effects of P. antipodarum on benthic resources, native benthic invertebrates, and benthic predators. We encourage biologists working in western USA estuaries to be alert to the possibility of encountering P. antipodarum in benthic habitats and predator diets.

A phase II trial of murine monoclonal antibody 17-1A and interferon-γ: Clinical and immunological data

Summary A group of 15 patients with metastatic colorectal adenocarcinoma received a combination of interferon (0.1 mg/m², days 1–15) and the murine monoclonal antibody 17-1A (400 mg, days 5, 7, 9 and 12). The treatment was tolerated with minimal toxicity. Of the 14 evaluable patients, 13 developed human antibody to murine 17-1A, with 11 patients demonstrating antibody to the variable region of 17-1A (anti-idiotype). Antibody to the variable region was inhibited by 17-1A but not by mouse immunoglobulin. Sera from patients with substantial anti-idiotype reactivity were capable of inhibiting the binding of murine 17-1A to antigen expressing LS174-T cells thus indicating the presence of antibody directed against the 17-1A combining site (mirror-image anti-idiotype). The median survival of the whole group was 56 weeks and there was no correlation between clinical response/survival and the development of anti-idiotype antibody.Supported by the Veterans Administration Medical Center and by Public Health Services grant CA 45 232 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services     

Enzymatic evidence for involvement of the methylmalonyl-CoA pathway in propionate oxidation by Syntrophobacter wolinii

Enzyme measurements were carried out with crude cell-free extracts of the propionate oxidizing coculture of Syntrophobacter wolinii and Desulfovibrio G11. Using cell-free extracts of a pure culture of Desulfovibrio G11 as a blank, most of the enzymes involved in the methylmalonyl-CoA pathway for propionate oxidation, including a propionyl-CoA: oxaloacetate transcarboxylase, were demonstrated in S. wolinii.     

Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals

The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.     

Highly Efficient Flexible Hybrid Nanocrystal‐Cu(In,Ga)Se2 (CIGS) Solar Cells

A novel scheme for hybridizing inkjet‐printed thin film Cu(In,Ga)Se₂ (CIGS) solar cells with self‐assembled clusters of nanocrystal quantum dots (NQDs), which provides a 10.9% relative enhancement of the photon conversion efficiency (PCE), is demonstrated. A non‐uniform layer of NQD aggregates is deposited between the transparent conductive oxide and a CdS/CIGS p‐n junction using low cost pulsed‐spray deposition. Hybridization significantly improves the external quantum efficiency of the hybrid devices in the absorption range of the NQDs and in the red to near‐IR parts of the spectrum. The low wavelength response enhancement is found to be induced by luminescent down‐shifting (LDS) from the NQD layer, while the increase at longer wavelengths is attributed to internal scattering from NQD aggregates. LDS is demonstrated using time‐resolved spectroscopy, and the morphology of the NQD layer is investigated in fluorescence microscopy and cross‐sectional transmission electron microscopy. The influence of the NQD dose on the PCE of the hybrid devices is investigated and an optimum value is obtained. The low costs and limited material consumptions associated with pulsed‐spray deposition make these flexible hybrid devices promising candidates to help push thin‐film photovoltaic technology towards grid parity.     

Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening

trans-Sialidase from Trypanosoma cruzi (TcTS) has emerged as a potential drug target for treatment of Chagas disease. Here, we report the results of virtual screening for the discovery of novel TcTS inhibitors, which targeted both the sialic acid and sialic acid acceptor sites of this enzyme. A library prepared from the Evotec database of commercially available compounds was screened using the molecular docking program GOLD, following the application of drug-likeness filters. Twenty-three compounds selected from the top-scoring ligands were purchased and assayed using a fluorimetric assay. Novel inhibitor scaffolds, with IC₅₀ values in the submillimolar range were discovered. The 3-benzothiazol-2-yl-4-phenyl-but-3-enoic acid scaffold was studied in more detail, and TcTS inhibition was confirmed by an alternative sialic acid transfer assay. Attempts to obtain crystal structures of these compounds with TcTS proved unsuccessful but provided evidence of ligand binding at the active site.