Expression of mammalian GPCRs in C. elegans generates novel behavioural responses to human ligands

Background  

G-protein-coupled receptors (GPCRs) play a crucial role in many biological processes and represent a major class of drug targets. However, purification of GPCRs for biochemical study is difficult and current methods of studying receptor-ligand interactions involve in vitro systems. Caenorhabditis elegans is a soil-dwelling, bacteria-feeding nematode that uses GPCRs expressed in chemosensory neurons to detect bacteria and environmental compounds, making this an ideal system for studying in vivo GPCR-ligand interactions. We sought to test this by functionally expressing two medically important mammalian GPCRs, somatostatin receptor 2 (Sstr2) and chemokine receptor 5 (CCR5) in the gustatory neurons of C. elegans.     

Biological Control of Sheep Parasites using Duddingtonia flagrans: Trials on Commercial Farms in Sweden

   

Trials were conducted on 3 commercial sheep farms in Sweden to assess the effect of administering spores of the nematode trapping fungus, Duddingtonia flagrans, together with supplementary feed to lactating ewes for the first 6 weeks from turn-out on pastures in spring. Also control groups of ewes, receiving only feed supplement, were established on all 3 farms. Groups were monitored by intensive parasitological investigation. The ewes and their lambs were moved in late June to saved pastures for summer grazing, the lambs receiving an anthelmintic treatment at this time. After approximately 6 weeks on summer pasture the lambs were weaned, treated a second time with anthelmintic, and returned to their original lambing pastures for finishing. Decisions as to when lambs were to be marketed were entirely at the discretion of the farmer co-operators. No difference in lamb performance was found between the two treatments on all three farms. This was attributed to the high levels of nutrition initially of the ewes limiting their post-partum rise in nematode faecal egg counts in spring, which in turn resulted in low levels of nematode infection on pastures throughout the autumn period. Additionally, pastures were of good quality for the lambs during the finishing period, so they grew at optimal rates as far as the farmers were concerned.     

Fertility assurance through extrapair fertilizations and male paternity defense

Extrapair paternity has been observed in many formally monogamous species. Male pursuit of extrapair fertilizations is explained by the advantages of having offspring that receive essential paternal care from other males. Since females are capable of exercising a degree of control over the post-copulatory sperm competition, extrapair paternity cannot persist unless it confers fitness benefits on cuckolding females. Thus, extrapair paternity involves cooperation between mated females and extrapair males. On the other hand, paired males frequently exhibit strategies that minimize their loss of paternity and/or conserve paternal investment if paternity is lost. Hence, extrapair attributes of diverse species and populations reported in the literature are particular solutions of evolutionary games involving gender-specific cuckolding/anti-cuckolding strategies. Here we use methods of evolutionary game theory to study the role of male paternity guarding strategies in situations where females seek extrapair fertilizations for reasons of genetic compatibility and/or in pursuit of genetic diversity for their offspring. Our results indicate that in these circumstances pursuit of extrapair fertilizations is the only evolutionary stable female strategy. Males, on the other hand, have two, mutually exclusive, evolutionary stable strategies: full time pursuit of extrapair fertilizations and a compromise strategy wherein they protect in-pair paternity during their mate's fertile periods and pursue extrapair paternity the rest of the time. The relative merits of these two strategies are determined by the efficiency of male in-pair paternity defense, breeding synchrony, fitness advantages of extrapair over in-pair offspring, and the intensity of competition for extrapair fertilizations from floater males.     

Cytologic appearance of toxic nodular goiter after thyrostatic treatment. A karyometric study

OBJECTIVE: To assess whether the cytologic appearance of aspirates from toxic nodular goiter is substantially modified during the course of therapy with thyrostatic drugs. STUDY DESIGN: Morphometric features of thyrocyte nuclei in aspirates obtained from nontoxic nodular goiter (NTNG), toxic nodular goiter before treatment (TNG-untreated) and toxic nodular goiter during thyrostatic administration (TNG-treated) were examined. The relationship between the degree of morphologic changes and the duration of therapy was evaluated. An analysis of the composition of aspirates was also performed. RESULTS: The sizes of thyrocyte nuclei in the TNG-untreated group were larger than in the NTNG and TNG-treated groups, and treatment with thyrostatics was accompanied by a gradual decrease in the sizes of thyrocyte nuclei. However, karyometric features showed a tendency to increase again in patients treated for longer than 1 year, with the variability of nuclear size in a smear (anisokaryosis) increasing more markedly than the mean size of nuclei. Moreover, in those patients, nuclei with visible nucleoli were found. CONCLUSION: Only long-term therapy with thyrostatic drugs leads to changes in the microscopic appearance of smears obtained by fine needle aspiration biopsy (FNAB) of the thyroid relevant to cytologic diagnosis. Thus, FNAB can be performed successfully after the onset of treatment with thyrostatics if the cytologist is informed of the time scale of treatment in each case.     

Bottom-up excitable models of phytoplankton blooms

A simple nutrient-phytoplankton model is used to explore the dynamics of phytoplankton blooms. The model exhibits excitable behaviour in the sense that a large scale outbreak can only be triggered when a critical nutrient threshold is exceeded. The model takes into account several features often neglected but whose combined effect proves very important: (i) rapid nutrient recycling associated with the microbial loop and patch formation; (ii) self-shading; and (iii) a bottom-up approach, whereby nutrient levels are responsible for both the triggering and the demise of the bloom. Although the literature is replete with studies of ‘top-down’ models in which zooplankton grazing control the triggering and demise of the bloom, bottom-up models are nevertheless appropriate in many circumstances. We provide a full mathematical investigation of the effects of these three different features in an excitable system framework.     

Immune response and virus population composition: HIV as a case study

Based on the current understanding of the immune response, we present what we believe to be a new model of intrahost virus dynamics. The model takes into account the relationship between virus replication rate and the level of antigen displayed by infected cells, and shows how the cell-directed immune response controls both virus load and virus replication rate. In contrast to conventional wisdom, it shows that the predominant virus variant does not necessarily have the highest replication rate. A strong immune response produces a selective advantage for latent viruses, whereas a deteriorating immune response invites in viruses of higher replication rates. The model is analysed in light of the well-studied HIV/AIDS disease progression, and shows how a wide range of major, seemingly unrelated issues in the study of HIV may be accounted for in a simple and unified manner.     

A model of phytoplankton blooms

A simple model that describes the dynamics of nutrient-driven phytoplankton blooms is presented. Apart from complicated simulation studies, very few models reported in the literature have taken this "bottom-up" approach. Yet, as discussed and justified from a theoretical standpoint, many blooms are strongly controlled by nutrients rather than by higher trophic levels. The analysis identifies an important threshold effect: a bloom will only be triggered when nutrients exceed a certain defined level. This threshold effect should be generic to both natural blooms and most simulation models. Furthermore, predictions are given as to how the peak of the bloom Pmax is determined by initial conditions. A number of counterintuitive results are found. In particular, it is shown that increasing initial nutrient or phytoplankton levels can act to decrease Pmax. Correct predictions require an understanding of such factors as the timing of the bloom and the period of nutrient buildup before the bloom.     

Modeling polio as a disease of development

Poliomyelitis is a disease which began to appear in epidemic proportions in the late 19th century, paradoxically, just at the time when living conditions and developments in health were transforming enormously for the better. We present a simple age-class model that explains this "disease of development" as a threshold phenomenon. Epidemics arise when improved conditions in hygiene are able to reduce disease transmission of polio amongst children below a critical threshold level. This generates a large susceptible adult population in which, under appropriate conditions, epidemics can propagate. The polio model is analysed in terms of its bifurcation properties and in terms of its non-equilibrium outbreak dynamics.