A common fold mediates vertebrate defense and bacterial attack

Proteins containing membrane attack complex/perforin (MACPF) domains play important roles in vertebrate immunity, embryonic development, and neural-cell migration. In vertebrates, the ninth component of complement and perforin form oligomeric pores that lyse bacteria and kill virus-infected cells, respectively. However, the mechanism of MACPF function is unknown. We determined the crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens, to 2.0 angstrom resolution. The MACPF domain reveals structural similarity with poreforming cholesterol-dependent cytolysins (CDCs) from Gram-positive bacteria. This suggests that lytic MACPF proteins may use a CDC-like mechanism to form pores and disrupt cell membranes. Sequence similarity between bacterial and vertebrate MACPF domains suggests that the fold of the CDCs, a family of proteins important for bacterial pathogenesis, is probably used by vertebrates for defense against infection.     

A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6). The proline-to-glutamine substitution at position 112, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II and appears to alter the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest an alternative mechanism for the pathogenesis of glomerular disease.     

Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension

The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone cells reach the olfactory bulb (OB) in rodents. However, the RMS in the adult human brain has been elusive. We demonstrate the presence of a human RMS, which is unexpectedly organized around a lateral ventricular extension reaching the OB, and illustrate the neuroblasts in it. The RMS ensheathing the lateral olfactory ventricular extension, as seen by magnetic resonance imaging, cell-specific markers, and electron microscopy, contains progenitor cells with migratory characteristics and cells that incorporate 5-bromo-2'-deoxyuridine and become mature neurons in the OB.     

On the Chemistry,Toxicology and Genetics of the Cyanobacterial Toxins,Microcystin, Nodularin,Saxitoxin and Cylindrospermopsin

The cyanobacteria or “blue-green algae”, as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Many aquatic, bloom-forming species of cyanobacteria are capable of producing biologically active secondary metabolites, which are highly toxic to humans and other animals. From a toxicological viewpoint, the cyanotoxins span four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins (irritant toxins). However, structurally they are quite diverse. Over the past decade, the biosynthesis pathways of the four major cyanotoxins: microcystin, nodularin, saxitoxin and cylindrospermopsin, have been genetically and biochemically elucidated. This review provides an overview of these biosynthesis pathways and additionally summarizes the chemistry and toxicology of these remarkable secondary metabolites.     

Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites

In the present study, 13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau’amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas genera have been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau’amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds. In addition, evaluation of the activity of the test alkaloids (2–14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids.     

Potato Cultivar and Seed Type Affect the Development of Systemic <Emphasis Type="Italic">Potato virus Y</Emphasis> (PVY<Superscript>N-Wi</Superscript>) Infection

Potato virus Y (PVY) infection is one of the greatest challenges to seed potato production in the United States. To determine how cultivar and seed type affect the development of systemic PVY infection, Russet Burbank and Russet Norkotah Colorado 3 cultivars were grown from two types of pre-nuclear seed (i.e., plantlets and minitubers) and Generation 3 (G3) tubers and challenged with PVY strain Wilga (PVY^N-Wi). Systemic PVY infection was measured by assaying spread of virus from the inoculation site to upper non-inoculated leaves. The Burbank cultivar had a lower incidence of systemic PVY infection compared to the incidence of systemic PVY that developed in the Colorado 3 cultivar. Furthermore, Burbank plants grown from G3 tubers had a lower incidence of systemic PVY infection, as compared to Burbank plants grown from plantlets. Together our results indicate that both cultivar and seed type affect the development of systemic PVY^N-Wi infections post-inoculation.     

Comparison of conventional and molecular techniques to investigate the intestinal microflora of rainbow trout (Oncorhynchus mykiss)

The concept of the use of probiotic organisms or prebiotic compounds to modify the fish gut microflora is becoming a popular topic for investigation. A major flaw in many such studies is a failure to consider fully the nature of the established microflora, which is to be modified pre-, or probiotically. Since it is widely accepted that a large proportion of bacteria are non-culturable, the use of conventional bacteriological (culture) techniques alone to investigate fish intestinal microflora may be expected to bias results. We report a study designed to investigate the normal intestinal microflora of rainbow trout (Oncorhynchus mykiss) using both conventional bacteriological and molecular methods.Over an 18 month period, the intestinal microflora of a single population of laboratory-raised rainbow trout was investigated. Bacteria isolated using bacteriological techniques were identified using the BiOLOG system and 16S rRNA gene sequencing. Dominant bacteria consistently were Aeromonas sp. and Carnobacterium piscicola, demonstrating that the microflora is stable in fish kept in defined conditions. Restriction Fragment Length Polymorphism (RFLP) and 16S rRNA gene sequence analysis was used to investigate anaerobic and non-culturable bacteria. An obligate anaerobe, Clostridium gasigenes, was shown to be among the dominating intestinal microflora.     

Fishes that rule the world: circumtropical distributions revisited

Briggs ( 1960 ) published the first checklist of circumtropical fishes with 107 species. This work served for a half century as the most comprehensive checklist of globally distributed fishes, but the intervening years witnessed many discoveries, and molecular data have changed the way we evaluate species. Here, we update the list guided by taxonomic revisions, phylogenies, phylogeographic data and DNA barcodes. The resulting list now includes 284 species. The dramatic increase is primarily due to two trends: (i) continued oceanic exploration leading to range revisions and species discoveries and (ii) public databases such as FishBase and the Catalogue of Fishes make range data more accessible. Five species were removed from the list as closer scrutiny revealed multiple taxa, 14 were removed due to updated range information, and 35 more are suspected to be species complexes. The species listed here are mostly pelagic and bathypelagic fishes. Euryhaline, anadromous, catadromous, freshwater, and with few exceptions, reef fishes do not achieve global distributions. The most species‐rich family of marine fishes (Gobiidae) is absent. The fishes with the longest pelagic larval stage (Anguillidae) are absent. In contrast, requiem sharks (Carcharhinidae), tunas (Scombridae), jacks (Carangidae), remoras (Echeneidae) and especially lanternfishes (Myctophidae) have multiple representatives. The combined evidence indicates that high mobility as an adult is a key requirement to achieve a global distribution. Many others are members of monotypic genera or families, indicating old lineages that did not diversify. We conclude that global ranges may promote persistence over evolutionary timescales, but also reduce opportunities for speciation.     

The Effects of Live and Artificial Diets on Feeding Performance of Cultured Winter Flounder,Pseudopleuronectes americanus,in the Wild: Survival,Feeding, Growth,and Nucleic Acid Analyses

This research, which is part of a larger study designed to assess the feasibility of winter flounder, Pseudopleuronectes americanus, stock enhancement in New Hampshire, identifies hatchery feeds that optimize feeding‐related performance of fish once released in the wild. Fish reared on post‐nauplii of brine shrimp, Artemia sp., white worms, Enchytraeus albidus, common burrower amphipods, Leptocheirus plumulosus, and formulated pellets were evaluated post‐release from in situ cages using survival, growth rate, feeding onset and incidence, stomach fullness, diet composition, and nucleic acid‐based condition as indicators of hatchery diet suitability. Amphipod‐reared fish had the highest mean stomach content index of all feed types, including wild fish. Wild and worm‐reared fish exhibited the most similar survival, overall stomach fullness, and diet composition profiles over time. Amphipod‐reared fish ranked highest in overall performance; however, if wild fish performance is viewed as the ideal for a stocked fish, worm‐reared fish performed optimally. This study describes hatchery feeding strategies that may ease the transition of flatfish released into the wild for stock enhancement.     

Using a well‐being approach to develop a framework for an integrated socio‐economic evaluation of professional fishing

The principles of Ecologically Sustainable Development and Ecosystem Based Fisheries Management require that fisheries be managed for social as well as environmental and economic objectives. Comprehensive assessments of the success of fisheries in achieving all three objectives are, however, rare. There are three main barriers to achieving integrated assessments of fisheries. Firstly, disciplinary divides can be considered “too hard” to bridge with inherent conflicts between the predominately empirical and deductive traditions of economics and biophysical sciences and the inductive and interpretative approach of much of the social sciences. Secondly, understanding of the social pillar of sustainability is less well developed. And finally, in‐depth analysis of the social aspects of sustainability often involves qualitative analysis and there are practical difficulties in integrating this with largely quantitative economic and ecological assessments. This article explores the social well‐being approach as a framework for an integrated evaluation of the social and economic benefits that communities in New South Wales, Australia, receive from professional fish harvesting. Using a review of existing literature and qualitative interviews with more than 160 people associated with the fishing industry the project was able to identify seven key domains of community well‐being to which the industry contributes. Identification of these domains provided a framework through which industry contributions could be further explored, through quantitative surveys and economic analysis. This framework enabled successful integration of social and economic, and both qualitative and quantitative information in a manner that enabled a comprehensive assessment of the value of the fishery.