Dispersal of Deep-Sea Larvae from the Intra-American Seas: Simulations of Trajectories using Ocean Models

Using data on ocean circulation with a Lagrangian larval transport model, we modeled the potential dispersal distances for seven species of bathyal invertebrates whose durations of larval life have been estimated from laboratory rearing, MOCNESS plankton sampling, spawning times, and recruitment. Species associated with methane seeps in the Gulf of Mexico and/or Barbados included the bivalve "Bathymodiolus" childressi, the gastropod Bathynerita naticoidea, the siboglinid polychaete tube worm Lamellibrachia luymesi, and the asteroid Sclerasterias tanneri. Non-seep species included the echinoids Cidaris blakei and Stylocidaris lineata from sedimented slopes in the Bahamas and the wood-dwelling sipunculan Phascolosoma turnerae, found in Barbados, the Bahamas, and the Gulf of Mexico. Durations of the planktonic larval stages ranged from 3 weeks in lecithotrophic tubeworms to more than 2 years in planktotrophic starfish. Planktotrophic sipunculan larvae from the northern Gulf of Mexico were capable of reaching the mid-Atlantic off Newfoundland, a distance of more than 3000?km, during a 7- to 14-month drifting period, but the proportion retained in the Gulf of Mexico varied significantly among years. Larvae drifting in the upper water column often had longer median dispersal distances than larvae drifting for the same amount of time below the permanent thermocline, although the shapes of the distance-frequency curves varied with depth only in the species with the longest larval trajectories. Even species drifting for >2 years did not cross the ocean in the North Atlantic Drift.     

Cardiomyocyte Antihypertrophic Effect of Adipose Tissue Conditioned Medium from Rats and Its Abrogation by Obesity is Mediated by the Leptin to Adiponectin Ratio

White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin–dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels.     

HIV-1 Nef disrupts antigen presentation early in the secretory pathway

Human immunodeficiency virus, type 1 Nef disrupts viral antigen presentation and promotes viral immune evasion from cytotoxic T lymphocytes. There is evidence that Nef acts early in the secretory pathway to redirect major histocompatibility complex class I (MHC-I) from the trans-Golgi network to the endolysosomal pathway. However, a competing model suggests that Nef acts much later by accelerating MHC-I turnover at the cell surface. Here we demonstrate that Nef targets early forms of MHC-I molecules in the endoplasmic reticulum by preferentially binding hypophosphorylated cytoplasmic tails. The Nef-MHC-I complex migrates normally into the Golgi apparatus but subsequently fails to arrive at the cell surface and become phosphorylated. Cell type-specific differences in the rate of MHC-I transport through the secretory pathway correlate with responsiveness to Nef and co-precipitation of adaptor protein 1 with the Nef.MHC-I complex. We propose that the assembly of a Nef.MHC-I.adaptor protein 1 complex early in the secretory pathway is important for Nef activity.     

The intestinal heme transporter revealed

The iron-containing porphyrin heme provides a rich source of dietary iron for mammals. The fact that animals can derive iron from heme implies the existence of a transporter that would transport heme from the gut lumen into intestinal epithelial cells. In this issue of Cell, Shayeghi, McKie, and co-workers (Shayeghi et al., 2005) now describe a heme transporter that is expressed in the apical region of epithelial cells in the mouse duodenum. Their identification of heme carrier protein 1 (HCP1) provides a major missing piece in our understanding of iron uptake and mammalian nutrition.     

Risk assessment for engineered bacteria used in biocontrol of fungal disease in agricultural crops

A plant growth promoting rhizobacterium (PGPR)Pseudomonas fluorescens SBW25 (WT) protects a number of crop plant species from damping-off caused by Pythium ultimum. A genetically modified, phenazine-1-carboxylic acid (PCA) producing variant, 23.10, carries on its chromosome a single copy of phzABCDEFG, under the control of the P tac constitutive promoter. The genetically modified biological control agent (GM-BCA), 23.10, has improved biocontrol activity when compared to wild type SBW25, and can effectively suppress Pythium spp. present at up to 100 times normal field infestations. GM-BCA inocula establish high population densities which persist well in the phytosphere of several crop plants including pea, wheat and sugar beet, effectively suppressed infection and promoted increase in total plant biomass. It also has an improved spectrum of activity over other plant phytopathogens such as Fusarium spp. Gaeumannomyces graminis var. tritici, Phytophtora cinnamomi and Rhizoctonia solani. However in developing BCAs and in particular GMBCAs it is important to determine whether their use has any adverse effect in the environment. Any observed changes following inoculation with wild type BCA or GM BCA in microbial diversity (bacteria and fungi) were negligible when assessed by either quantitive selective plate count methods (CFU/g) or culture independent molecular assays (SSU rRNA based PCR-DGGE). Rhizosphere community diversity profiles (DGGE) in infected plants in the presence of inocula were highly similar to disease free systems. Histological assessment of the impact of inocula on established functional mycorrhizae associations were conducted on cores collected from an established field margin grassland pasture. No adverse impact on mycorrhizal colonization and root infection were recorded after addition of WT or GM-BCA bacterial inocula as a soil drench. This approach and the related culturable and culture independent methods have recorded only a minor, transient perturbation to microbial communities, but as far as we are aware this is the first direct demonstration that a functional, AFC producing GMM also has only a transient impact on mycorrhizal associations in established plant communities. In all instances studied the plant species, plant stage of development and disease, damping-off, had a greater impact on changes in rhizosphere diversity than the presence of an introduced GM bacterial inocula.     

The contribution of Plasmodium chabaudi to our understanding of malaria

Malaria kills close to a million people every year, mostly children under the age of five. In the drive towards the development of an effective vaccine and new chemotherapeutic targets for malaria, field-based studies on human malaria infection and laboratory-based studies using animal models of malaria offer complementary opportunities to further our understanding of the mechanisms behind malaria infection and pathology. We outline here the parallels between the Plasmodium chabaudi mouse model of malaria and human malaria. We will highlight the contribution of P. chabaudi to our understanding of malaria in particular, how the immune response in malaria infection is initiated and regulated, its role in pathology, and how immunological memory is maintained. We will also discuss areas where new tools have opened up potential areas of exploration using this invaluable model system.     

Medicinal chemistry approaches to avoid aldehyde oxidase metabolism

Aldehyde oxidase (AO) is a molybdenum-containing enzyme distributed throughout the animal kingdom and capable of metabolising a wide range of aldehydes and N-heterocyclic compounds. Although metabolism by this enzyme in man is recognised to have significant clinical impact where human AO activity was not predicted by screening in preclinical species, there is very little reported literature offering real examples where drug discoverers have successfully designed away from AO oxidation. This article reports on some strategies adopted in the Pfizer TLR7 agonist programme to successfully switch off AO metabolism that was seen principally in the rat.     

Physiological costs of growing fast: does accelerated growth reduce pay-off in adult fitness?

Accumulating evidence suggests that, in contrast to earlier assumptions, juvenile growth rates are optimised by means of natural and sexual selection rather than maximised to be as fast as possible. Owing to the generally accepted advantage of growing fast to adulthood, such adaptive variation strongly implies the existence of costs attached to rapid growth. By using four populations of protandrous copper butterflies with known differences in intrinsic growth rates within and across populations, we investigate a potential trade-off between rapid growth and the proportionate weight loss at metamorphosis. While controlling for effects of pupal time and mass, we demonstrate that (1) protandrous males, exhibiting higher growth rates, suffer a higher weight loss than females throughout, that (2) population differences in weight loss generally follow known differences in growth rates, and that (3) males have by 6 higher metabolic rates than females during pupal development. These results support the notion that a higher weight loss during the development to adulthood may comprise a physiological cost of rapid development, with the pay-off of accelerated growth being reduced by a disproportionally smaller adult sizeCo-ordinating editor: Leimer     

Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1

Macrophages are essential for normal wound repair and many of their effects on healing wounds are likely to be mediated by the secretion of cytokines. This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers. RNA for all four cytokines can be detected in wound inflammatory cells by polymerase chain reaction amplification throughout the first 7 days. Cachectin/TNF and IL 1 protein levels peaked on the first day after wound chamber implantation, and MIP-1 and MIP-2 were detected only on day 3. The data suggest that these cytokines participate in the early inflammatory response to wounding.