Cell cycle arrest induced by the bacterial adenylate cyclase toxins from Bacillus anthracis and Bordetella pertussis

Bacillus anthracis oedema toxin (ET) and Bordetella pertussis adenylate cyclase toxin (ACT) enter host cells and produce cAMP. To understand the cellular consequences, we exposed J774 cells to these toxins at ng ml(-1) (pM) concentrations, then followed cell number and changes in cell signalling pathways. Under these conditions, both toxins produce a concentration-dependent inhibition of cell proliferation without cytotoxicity. ET and ACT increase the proportion of cells in G(1) /G(0) and reduce S phase, such that a single addition of ET or ACT inhibits cell division for 3-6 days. Treatment with ET or ACT produces striking changes in proteins controlling cell cycle, including virtual elimination of phosphorylated ERK 1/2 and Cyclin D1 and increases in phospho-CREB and p27(Kip1) . Importantly, PD98059, a MEK inhibitor, elicits a comparable reduction in Cyclin D1 to that produced by the toxins and blocks proliferation. These data show that non-lethal concentrations of ET and ACT impose a prolonged block on the proliferation of J774 cells by impairment of the progression from G(1) /G(0) to S phase in a process involving cAMP-mediated increases in phospho-CREB and p27(Kip1) and reductions in phospho-ERK 1/2 and Cyclin D1. This phenomenon represents a new mechanism by which these toxins affect host cells.     

Short rotation coppice culture of willows and poplars as energy crops on metal contaminated agricultural soils

Phytoremediation, more precisely phytoextraction, has been placed forward as an environmental friendly remediation technique, that can gradually reduce increased soil metal concentrations, in particular the bioavailable fractions. The aim of this study was to investigate the possibilities of growing willows and poplars under short rotation coppice (SRC) on an acid, poor, sandy metal contaminated soil, to combine in this way soil remediation by phytoextraction on one hand, and production of biomass for energy purposes on the other. Above ground biomass productivities were low for poplars to moderate for willows, which was not surprising, taking into account the soil conditions that are not very favorable for growth of these trees. Calculated phytoextraction efficiency was much longer for poplars than these for willows. We calculated that for phytoextraction in this particular case it would take at least 36 years to reach the legal threshold values for cadmium, but in combination with production of feedstock for bioenergy processes, this type of land use can offer an alternative income for local farmers. Based on the data of the first growing cycle, for this particular case, SRC of willows should be recommended.     

Effects of heterogeneous and clustered contact patterns on infectious disease dynamics

The spread of infectious diseases fundamentally depends on the pattern of contacts between individuals. Although studies of contact networks have shown that heterogeneity in the number of contacts and the duration of contacts can have far-reaching epidemiological consequences, models often assume that contacts are chosen at random and thereby ignore the sociological, temporal and/or spatial clustering of contacts. Here we investigate the simultaneous effects of heterogeneous and clustered contact patterns on epidemic dynamics. To model population structure, we generalize the configuration model which has a tunable degree distribution (number of contacts per node) and level of clustering (number of three cliques). To model epidemic dynamics for this class of random graph, we derive a tractable, low-dimensional system of ordinary differential equations that accounts for the effects of network structure on the course of the epidemic. We find that the interaction between clustering and the degree distribution is complex. Clustering always slows an epidemic, but simultaneously increasing clustering and the variance of the degree distribution can increase final epidemic size. We also show that bond percolation-based approximations can be highly biased if one incorrectly assumes that infectious periods are homogeneous, and the magnitude of this bias increases with the amount of clustering in the network. We apply this approach to model the high clustering of contacts within households, using contact parameters estimated from survey data of social interactions, and we identify conditions under which network models that do not account for household structure will be biased.     

Evaluating paint rollers as an intervention for alopecia in monkeys in the laboratory (Macaca nemestrina)

Adult female macaques (Macaca nemestrina) in the laboratory with alopecia from known or suspected overgrooming were subjects in a study evaluating effectiveness of a grooming device. The intervention evaluated was a paint roller on a metal bar hung on the cage, replaced weekly for 6 weeks. In a within-subjects design, 6 monkeys were randomly assigned to first experience the paint roller (PR) and later the control (C) condition (roller bar only); 6 monkeys were randomly assigned to C followed by PR. Coat condition scores quantifying alopecia were taken cageside weekly. During PR, PR use was scored 3 times a week based on wear. Alopecia scores during PR did not differ significantly from C. Although all the monkeys used the paint rollers, PR use scores did not correlate significantly with improvement in coat condition. Paint rollers do not appear to be an effective intervention for alopecia from overgrooming.     

Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes

A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3-aPKC complex to leave the cortex. Our findings illustrate how microtubules, independently of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC.     

The skeletal organic matrix from Mediterranean coral Balanophyllia europaea influences calcium carbonate precipitation

Scleractinian coral skeletons are made mainly of calcium carbonate in the form of aragonite. The mineral deposition occurs in a biological confined environment, but it is still a theme of discussion to what extent the calcification occurs under biological or environmental control. Hence, the shape, size and organization of skeletal crystals from the cellular level through the colony architecture, were attributed to factors as diverse as mineral supersaturation levels and organic mediation of crystal growth. The skeleton contains an intra-skeletal organic matrix (OM) of which only the water soluble component was chemically and physically characterized. In this work that OM from the skeleton of the Balanophyllia europaea, a solitary scleractinian coral endemic to the Mediterranean Sea, is studied in vitro with the aim of understanding its role in the mineralization of calcium carbonate. Mineralization of calcium carbonate was conducted by overgrowth experiments on coral skeleton and in calcium chloride solutions containing different ratios of water soluble and/or insoluble OM and of magnesium ions. The precipitates were characterized by diffractometric, spectroscopic and microscopic techniques. The results showed that both soluble and insoluble OM components influence calcium carbonate precipitation and that the effect is enhanced by their co-presence. The role of magnesium ions is also affected by the presence of the OM components. Thus, in vitro, OM influences calcium carbonate crystal morphology, aggregation and polymorphism as a function of its composition and of the content of magnesium ions in the precipitation media. This research, although does not resolve the controversy between environmental or biological control on the deposition of calcium carbonate in corals, sheds a light on the role of OM, which appears mediated by the presence of magnesium ions.     

The first sequenced carnivore genome shows complex host-endogenous retrovirus relationships

Host-retrovirus interactions influence the genomic landscape and have contributed substantially to mammalian genome evolution. To gain further insights, we analyzed a female boxer (Canis familiaris) genome for complexity and integration pattern of canine endogenous retroviruses (CfERV). Intriguingly, the first such in-depth analysis of a carnivore species identified 407 CfERV proviruses that represent only 0.15% of the dog genome. In comparison, the same detection criteria identified about six times more HERV proviruses in the human genome that has been estimated to contain a total of 8% retroviral DNA including solitary LTRs. These observed differences in man and dog are likely due to different mechanisms to purge, restrict and protect their genomes against retroviruses. A novel group of gammaretrovirus-like CfERV with high similarity to HERV-Fc1 was found to have potential for active retrotransposition and possibly lateral transmissions between dog and human as a result of close interactions during at least 10.000 years. The CfERV integration landscape showed a non-uniform intra- and inter-chromosomal distribution. Like in other species, different densities of ERVs were observed. Some chromosomal regions were essentially devoid of CfERVs whereas other regions had large numbers of integrations in agreement with distinct selective pressures at different loci. Most CfERVs were integrated in antisense orientation within 100 kb from annotated protein-coding genes. This integration pattern provides evidence for selection against CfERVs in sense orientation relative to chromosomal genes. In conclusion, this ERV analysis of the first carnivorous species supports the notion that different mammals interact distinctively with endogenous retroviruses and suggests that retroviral lateral transmissions between dog and human may have occurred.     

Fish consumption measured during pregnancy and risk of cardiovascular diseases later in life: an observational prospective study

Previous studies have indicated a protective effect of long chain n-3 PUFAs against cardiovascular disease; however, the overall evidence remains uncertain, and there is a general lack of knowledge in the field of cardiovascular epidemiology in women. Therefore, the objective of this study was to explore the association between fish intake and cardiovascular disease among 7429 women from a prospective pregnancy cohort in Aarhus, Denmark, who were followed for 12-17 years. Exposure information derived from a questionnaire sent to the women in gestation week 16, and daily fish consumption was quantified based on assumptions of standard portion sizes and food tables. Information on admissions to hospital was obtained from the Danish National Patient Registry and diagnoses of hypertensive, cerebrovascular and ischaemic heart disease were used to define the outcome: cardiovascular disease. During the follow-up period 263 events of cardiovascular disease were identified. Overall, there was no association between cardiovascular disease and fish intake, confidence intervals for effect estimates in the different fish intake groups were wide, overlapped and for all but one they encompassed unity. Restricting the analysis to women who had reported the same fish intake in a questionnaire in gestation week 30 did not alter these findings. In conclusion, our data from a prospective cohort of relatively young and initially healthy women from Aarhus linked with information from registries could not substantiate a protective effect of fish intake against cardiovascular disease.