Sheep Movement Networks and the Transmission of Infectious Diseases

Background and Methodology

Various approaches have been used to investigate how properties of farm contact networks impact on the transmission of infectious diseases. The potential for transmission of an infection through a contact network can be evaluated in terms of the basic reproduction number, R ₀. The magnitude of R ₀ is related to the mean contact rate of a host, in this case a farm, and is further influenced by heterogeneities in contact rates of individual hosts. The latter can be evaluated as the second order moments of the contact matrix (variances in contact rates, and co-variance between contacts to and from individual hosts). Here we calculate these quantities for the farms in a country-wide livestock network: >15,000 Scottish sheep farms in each of 4 years from July 2003 to June 2007. The analysis is relevant to endemic and chronic infections with prolonged periods of infectivity of affected animals, and uses different weightings of contacts to address disease scenarios of low, intermediate and high animal-level prevalence.

Principal Findings and Conclusions

Analysis of networks of Scottish farms via sheep movements from July 2003 to June 2007 suggests that heterogeneities in movement patterns (variances and covariances of rates of movement on and off the farms) make a substantial contribution to the potential for the transmission of infectious diseases, quantified as R ₀, within the farm population. A small percentage of farms (<20%) contribute the bulk of the transmission potential (>80%) and these farms could be efficiently targeted by interventions aimed at reducing spread of diseases via animal movement.     

Purinergic Membrane Receptors as Targets for the Effect of Purotoxin 1, a Component of Venom of Spiders from the <Emphasis Type="Italic">Geolycosa</Emphasis> Genus

We examined effects of purotoxin 1 (PT1), a component of the venom of Geolycosa spiders, on a few voltageand ligand-operated ion channels present in the plasma membrane of sensory neurons from the rat dorsal root ganglia (DRGs). Purotoxin 1 in a 100 nM concentration evoked no changes in ion currents through voltage-operated sodium, potassium, and calcium channels in the membranes of isolated sensory neurons. This agent was also found to be ineffective with respect to capsaicin-sensitive receptor-channel complexes (TRPV1). Testing of the effects of PT1 on purinergic receptor-channel complexes P2X3, P2X2, and P2X2/3 showed that this toxin is a highly selective blocker of exclusively P2X3 receptors. The selectivity of action of PT1 demonstrated in our experiments shows that it is a unique agent, which opens up new prospects in the studies of structural/functional peculiarities of receptor-channel complexes P2X3 as a peripheral link of the nociception system.     

Recognition sites of monoclonal antibodies A4 and A24 in the α-latrotoxin molecule

α-Latrotoxin (α-LTX) binding sites to functionally active monoclonal antibodies (MA) A4 and A24 were localized using three approaches: hydrolysis of the toxin followed by theN-terminal sequencing of immunoreactive peptides; the study of antibody interaction with several recombinant α-LTX fragments; Western immunoblotting of synthetic overlapping peptides (6–8 aa) whose structures correspond to that of the immunoreactive α-LTX fragment. It was shown that the MA A4 epitope is located within the F²³⁴-M²⁹⁴ protein fragment and that MA A24 interacts with the fragment³⁴⁷FDKDIT³⁵².     

EXAFS studies of the calcium salts of natural DNA and polydA:polydT

Preliminary EXAFS experiments were carried out on film of the Ca salts of the synthetic polynucleotide polydA:polydT at 95%, 81%, and 76% relative humidity (r.h.) and for the Ca salt of chicken erythrocyte DNA at 81% r.h. (approximately 43% GC pairs). Detailed analysis of EXAFS data shows that the Ca2+ ion is in fairly close proximity (within 4 A) to a number of phosphorous atoms. This is in contradiction with the recently proposed model, which assumes a close coordination between the cations and the purine and pyrimidine bases deep inside the polynucleotide molecule, so that the distance to the nearest phosphorous atoms must not be less than 5 A. Instead, the EXAFS results suggest that the Ca2+ ions are, for the most part, located at the periphery of individual polydA:polydT (or DNA) molecules, possibly serving as intermolecular links.     

Production of monoclonal antibodies to the prion protein and their characterization

Antibodies to the prion protein (PrP), particularly, monoclonal antibodies, are necessary tools in the diagnostics and study of prion diseases and potential means of their immunotherapy. For the production of monoclonal antibodies, BALB/c mice were immunized by a recombinant bovine PrP. Three stable hybridomas producing antibodies of IgM class were prepared. The antibodies were bound to PrP in a solid-phase enzyme immunoassay and immunoblotting. The epitope mapping accomplished with the use of synthetic peptides showed that an epitope located in region 25–36 of PrP corresponds to one antibody, and epitopes located in region 222–229, to the other two. The antibodies to fragment 222–229 purified by affinity chromatography recognized with a high specificity conglomerates of a pathogenic prion in the brain tissue of cows suffering from spongiform encephalopathy. Thus, in nontransgenic mice, PrP-specific monoclonal antibodies were produced, useful in studies and diagnostics of prion diseases.     

Last glacial maximum biomes reconstructed from pollen and plant macrofossil data from northern Eurasia

Pollen and plant macrofossil data from northern Eurasia were used to reconstruct the vegetation of the last glacial maximum (LGM: 18,000 ± 2000 ¹⁴C yr bp ) using an objective quantitative method for interpreting pollen data in terms of the biomes they represent ( Prentice et al., 1996 ). The results confirm previous qualitative vegetation reconstructions at the LGM but provide a more comprehensive analysis of the data. Tundra dominated a large area of northern Eurasia (north of 57°N) to the west, south and east of the Scandinavian ice sheet at the LGM. Steppe‐like vegetation was reconstructed in the latitudinal band from western Ukraine, where temperate deciduous forests grow today, to western Siberia, where taiga and cold deciduous forests grow today. The reconstruction shows that steppe graded into tundra in Siberia, which is not the case today. Taiga grew on the northern coast of the Sea of Azov, about 1500 km south of its present limit in European Russia. In contrast, taiga was reconstructed only slightly south of its southern limit today in south‐western Siberia. Broadleaved trees were confined to small refuges, e.g. on the eastern coast of the Black Sea, where cool mixed forest was reconstructed from the LGM data. Cool conifer forests in western Georgia were reconstructed as growing more than 1000 m lower than they grow today. The few scattered sites with LGM data from the Tien‐Shan Mountains and from northern Mongolia yielded biome reconstructions of steppe and taiga, which are the biomes growing there today.     

Nitric oxide donor increases the efficiency of cytostatic therapy and retards the development of drug resistance.

The potentiality to increase the chemotherapeutic effectiveness of some cytostatics in low, subtherapeutic doses in combination with nitric oxide (NO) donor has been shown. This type of combined therapy results in significant increase in life span and number of survivors among mice bearing leukemias P388 and L-1210. A similar effect was observed for intracerebral leukemia P388 transplantation. In this case the life span of mice treated with cyclophosphamide and NO donor increased by three times in comparison to therapy with cyclophosphamide alone. The coinjection of nitric oxide donor and cytostatics improved the antimetastatic activity of the cytostatics: the index of melanoma B16 metastasis inhibition at the cyclophosphamide monotherapy is 50%; on addition of NO donor the index is over 80%. Comparative studies of NO donor (organic nitrate) and a similar compound in which ONO(2) moieties were replaced by OH groups demonstrated that the presence of NO(2) is required for adjuvant activity of compounds and confirmed that nitric oxide modifies the antitumor effects of cytostatics. It is shown also that nitric oxide donor retards the development of drug resistance to cyclophosphamide.     

Action of surface-active substances on biological membranes IV. Hemolytic and membrane-perturbing action of homologous series of β-d-glucopyranosyl-1-alkylphosphates

The hemolytic action of a homologous series of β-d-glucopyranosyl-1-alkylphosphates on human erythrocytes has been examined. The agent's affinity for the red cell membrane and the mean number of the agent's molecules which, upon interaction with an erythrocyte, make it undergo hemolysis have been measured. The contribution of the head group and that of a CH₂ group of the surfactants to the free energy of the agents' binding to the cell membrane have been estimated. The effect of the surfactants on the red cell volume and the lytic concentrations of the agents have been measured. The contribution of a CH₂ group to the free energy of the interaction of the amphiphiles embedded in the membrane bilayer with their environment has been evaluated and is proposed to be used as a measure of the membrane matrix stability.