Spatio-temporal analysis of cetacean strandings and bycatch in a UK fisheries hotspot

Marine vertebrate strandings data can provide insights into the long-term dynamics of cetacean populations, and the threats they face. We investigate whether the spatio-temporal patterns of cetacean strandings around Cornwall, SW Britain, have changed in the past century. Analysis of strandings from 1911 to 2006 (n = 2,257) show that, since the mid-1970s, the relative frequency of strandings of common dolphins (Delphinus delphis), harbour porpoises (Phocoena phocoena) and pilot whales (Globicephala melas) has increased significantly. Seasonal peaks in strandings frequencies are apparent, between December and March for harbour porpoises and common dolphins, and between November and January for pilot whales. There were significant positive trends in the number of common dolphin and harbour porpoise strandings, as a proportion of total strandings, over time. Strandings of common dolphins, porpoises and all other species occur more frequently on the south coast of Cornwall. A total of 415 cetaceans were subject to full veterinary necropsy to determine cause of death, between 1990 and 2006, and 253 (61%) of these individuals were determined to have died due to bycatch in fishing gear. Analyses of industrialised fishing pressure in UK waters show the seas around Cornwall to be one of the most heavily fished areas of the UK. We suggest a number of factors that could be responsible for the recent increases in cetacean strandings in southwest UK waters in recent years, including survey effort, as well as abundance and range shifts that are potentially linked with climate change. Although detectable levels of bycatch rate have not increased over time, fisheries interactions are in significant part responsible for mortality patterns and are worthy of more detailed investigation. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Overexpression of the lemon basil alpha-zingiberene synthase gene increases both mono- and sesquiterpene contents in tomato fruit

alpha-Zingiberene synthase (ZIS), a sesquiterpene synthase gene that was isolated from lemon basil (Ocimum basilicum L.), encodes an enzyme that catalyzes the formation of alpha-zingiberene, and other sesquiterpenes, from farnesyl diphosphate. Transgenic tomato fruits overexpressing ZIS under the control of the fruit ripening-specific tomato polygalacturonase promoter (PG) accumulated high levels of alpha-zingiberene (224-1000 ng g(-1) fresh weight) and other sesquiterpenes, such as alpha-bergamotene, 7-epi-sesquithujene, beta-bisabolene and beta-curcumene, whereas no sesquiterpenes were detected in non-transformed control fruits. The ZIS-transgenic fruits also produced monoterpenes, such as alpha-thujene, alpha-pinene, beta-phellandrene and gamma-terpinene (1-22 ng g(-1) fresh weight), which were either not detected or were found only in minute concentrations in control fruits. Recombinant ZIS overexpressed in Escherichia coli catalyzed the formation of these monoterpenes from geranyl diphosphate. As the ZIS protein apparently lacks a transit peptide, and is localized in the cytosol, the production of monoterpenes in the transgenic tomatoes suggests that a pool of geranyl diphosphate is available in the cytosol. The phenotype of the ZIS-transgenic tomatoes was the same as that for wild-type tomatoes, with regard to plant vigor and shape, but transgenic plants exhibited a small decrease in lycopene content. This study thus showed that the synthesis of both mono- and sesquiterpenes can be enhanced by the ectopic expression of a single transgene in tomato fruit, and it further demonstrated the interconnection between the pools of terpenoid precursors in the plastids and the cytosol.     

BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character

This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures.     

Neuronal nitric oxide synthase knock-out mice show impaired cognitive performance.

Nitric oxide (NO) plays a role in a series of neurobiological functions, underlying behavior and memory. The functional role of nNOS derived NO in cognitive functions, however, is elusive. We decided to study cognitive functions in the Morris water maze (MWM) and the multiple T-maze (MTM) in 3-month-old male nNOS-knock-out mice (nNOS KO). To study the influence of neurology and behavior, we performed tests in an observational battery, the rota-rod, the elevated plus maze (EPM), the open field (OF), and a social interaction test. In the memory and relearning task of the MWM, most nNOS KO failed whereas performing better in the MTM. nNOS KO displayed significantly increased frequency of grooming, center crossings, and entries into the center in the OF. The observational battery revealed significantly increased scores for touch-escape reaction, body position, locomotion, and pelvic- and tail-elevation together with reduced vocalization. In the EPM, the time spent in the closed arm and the grooming frequency were significantly increased whereas urination was absent. We conclude that nNOS KO show impaired spatial performance in the MWM and herewith confirm the role of nNOS in cognitive functions such as processing, maintenance, and recall of memory. It must be taken into account that the major behavioral findings of increased grooming and anxiety-related behaviors may have led to impaired function in the MWM. The fact that nNOS KO performed well in the MTM, reflecting a low stress situation points to the interpretation that nNOS inhibition affects cognitive functions under stressful conditions (MWM) only.     

Type V protein secretion pathway: the autotransporter story.

Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function.     

Detection of HSV type-1 and type-2 IgG using an in vitro PCA based homogeneous immunoassay

Enzyme immunoassays (EIAs) are widely used in the clinical laboratory and research institutes for the detection of biologically relevant analytes. Almost all EIAs are heterogeneous in nature and require multiple steps of process. In contrast, homogeneous immunoassays (HA) offer a simplified one-step approach with a number of potential advantages over contemporary heterogeneous EIAs such as higher throughput and greater clinical utility. Utilizing TEM-1 β-lactamase as a reporter enzyme, we have developed HAs based on in vitro protein fragment complementation (PCA) for the detection of antibodies and potentially be used for antigens or other biomarkers. In this proof-of-principle study we demonstrate the successful in vitro differentiation of anti-herpes simplex virus (HSV) type-1 and type-2 Immunoglobulin G (IgG) in human serum with high sensitivity and specificity.     

Proinflammatory activity of TWEAK on human dermal fibroblasts and synoviocytes: blocking and enhancing effects of anti-TWEAK monoclonal antibodies

Human tumour necrosis factor (TNF)-like weak inducer of apoptosis (hTWEAK) and two anti-hTWEAK mAbs were tested for their ability to elicit or block inflammatory responses in cultured human dermal fibroblasts and synoviocytes. Incubation with hTWEAK increased the production of prostaglandin E₂, matrix metalloproteinase-1 (MMP-1), IL-6, and the chemokines IL-8, RANTES (regulated on activation, normal T expressed and secreted) and interferon-γ-inducible protein-10 (IP-10) in culture supernatant of fibroblasts and synoviocytes. In combination with TNF or IL-1β, hTWEAK further stimulated the secretion of prostaglandin E₂, MMP-1, IL-6 and IL-8 up to fourfold, and IP-10 and RANTES up to 70-fold compared to TNF or IL-1β alone. An anti-hTWEAK mAb, BCB10, blocked the effects of hTWEAK, whereas hTWEAK crosslinked by the anti-hTWEAK mAb, BEB3, further stimulated the inflammatory response of fibroblasts and synoviocytes. The anti-hTWEAK mAbs were ineffective in blocking or increasing the responses of TNF or IL-1β and blocking anti-TNF mAb was ineffective in preventing the responses to TWEAK. These results were also confirmed at the RNA level for MMP-1, macrophage chemoattractant protein-1, RANTES, macrophage inflammatory protein-1α, IP-10 and IL-8. TWEAK in synergism with IL-1 and TNF may be an additional cytokine that plays a role in destructive chronic arthritic diseases.