Geographic and topographic determinants of local FMD transmission applied to the 2001 UK FMD epidemic

Background

Models of Foot and Mouth Disease (FMD) transmission have assumed a homogeneous landscape across which Euclidean distance is a suitable measure of the spatial dependency of transmission. This paper investigated features of the landscape and their impact on transmission during the period of predominantly local spread which followed the implementation of the national movement ban during the 2001 UK FMD epidemic. In this study 113 farms diagnosed with FMD which had a known source of infection within 3 km (cases) were matched to 188 control farms which were either uninfected or infected at a later timepoint. Cases were matched to controls by Euclidean distance to the source of infection and farm size. Intervening geographical features and connectivity between the source of infection and case and controls were compared.

Results

Road distance between holdings, access to holdings, presence of forest, elevation change between holdings and the presence of intervening roads had no impact on the risk of local FMD transmission (p > 0.2). However the presence of linear features in the form of rivers and railways acted as barriers to FMD transmission (odds ratio = 0.507, 95% CIs = 0.297,0.887, p = 0.018).

Conclusion

This paper demonstrated that although FMD spread can generally be modelled using Euclidean distance and numbers of animals on susceptible holdings, the presence of rivers and railways has an additional protective effect reducing the probability of transmission between holdings.

     

Binding, hydration, and decarboxylation of the reaction intermediate glutaconyl-coenzyme A by human glutaryl-CoA dehydrogenase.

Glutaconyl-coenzyme A (CoA) is the presumed enzyme-bound intermediate in the oxidative decarboxylation of glutaryl-CoA that is catalyzed by glutaryl-CoA dehydrogenase. We demonstrated glutaconyl-CoA bound to glutaryl-CoA dehydrogenase after anaerobic reduction of the dehydrogenase with glutaryl-CoA. Glutaryl-CoA dehydrogenase also has intrinsic enoyl-CoA hydratase activity, a property of other members of the acyl-CoA dehydrogenase family. The enzyme rapidly hydrates glutaconyl-CoA at pH 7.6 with a k(cat) of 2.7 s(-1). The k(cat) in the overall oxidation-decarboxylation reaction at pH 7.6 is about 9 s(-1). The binding of glutaconyl-CoA was quantitatively assessed from the K(m) in the hydratase reaction, 3 microM, and the K(i), 1.0 microM, as a competitive inhibitor of the dehydrogenase. These values compare with K(m) and K(i) of 4.0 and 12.9 microM, respectively, for crotonyl-CoA. Glu370 is the general base catalyst in the dehydrogenase that abstracts an alpha-proton of the substrate to initiate the catalytic pathway. The mutant dehydrogenase, Glu370Gln, is inactive in the dehydrogenation and the hydratase reactions. However, this mutant dehydrogenase decarboxylates glutaconyl-CoA to crotonyl-CoA without oxidation-reduction reactions of the dehydrogenase flavin. Addition of glutaconyl-CoA to this mutant dehydrogenase results in a rapid, transient increase in long-wavelength absorbance (lambda(max) approximately 725 nm), and crotonyl-CoA is found as the sole product. We propose that this 725 nm-absorbing species is the delocalized crotonyl-CoA anion that follows decarboxylation and that the decay is the result of slow protonation of the anion in the absence of the general acid catalyst, Glu370(H(+)). In the absence of detectable oxidation-reduction, the data indicate that oxidation-reduction of the dehydrogenase flavin is not essential for decarboxylation of glutaconyl-CoA.     

Recent shoreline changes in the Volta River delta,West Africa: the roles of natural processes and human impacts§

The Volta River delta developed as an asymmetric lobe in a tectonic offset on the coast of Ghana. The delta comprises a large curvilinear spit that widens in its central portion due to the adjunction of successive sandy beach ridges. The appearance of a distinct spit, in lieu of a continuous barrier from the present mouth of the Volta River to the Bight of Benin coast, may be an outgrowth of a natural change in the location of the mouth of the Volta. The spit marks a segmentation of the unique sand drift cell that hitherto prevailed on this bight coast. Spit growth has been accompanied by a wave of erosion over the last century of the immediate downdrift sector of the bight coast, endangering the town of Keta. Erosion since the 1960s may have been aggravated by the construction of the Akosombo hydropower dam. The tip of the spit has recently welded to the shoreline, thus assuring resumption of sand supply from the Volta towards the rest of this formerly sand-starved sector of the bight coast. Blocking of sediment by the Akosombo Dam is, in due course, likely to become the overarching factor in delta shoreline stability.     

Sexually dimorphic gall structures correspond to differential phytohormone contents in male and female wasp larvae

Sexually dimorphic galls are rare among gall‐inducing insects and the reason for their occurrence is unknown. The pteromalid wasp Trichilogaster acaciaelongifoliae, which induces galls on Acacia longifolia, is one such species. In the present study, the anatomical and physiological attributes of male and female galls of T. acaciaelongifoliae are examined and compared. Histological preparations are used to characterize anatomical differences between male and female gall chambers. Bioassays, high‐performance liquid chromatography‐mass spectrometry and an enzyme immunoassay are used to measure concentrations of auxin and cytokinin in normal buds, galled tissues, and larvae of both sexes. Female chambers are found to be 3.3‐fold larger, and are associated with 1.5‐fold more storage tissue and 3.5‐fold more vascular tissues than male chambers. Tissues from female chambers induce stronger cytokinin‐like bioactivity than tissues from male chambers. Female larvae have considerably higher concentrations of cytokinin free bases, ribosides, glucosides and monophosphates than male larvae; higher auxin‐like bioactivity than in normal or galled plant tissues; and almost twice the concentration of auxin than male larvae. Both male and female larvae contain much higher auxin concentrations than either galled or normal plant tissues. These findings suggest that differing levels of phytohormones are involved in the development of sexual dimorphism of gall structures in this species.     

Laparoscopic hysterectomy with or without pelvic lymphadenectomy or sampling in a high-risk series of patients with endometrial cancer

Background

The purpose of the study was to determine the outcome of all patients with endometrial adenocarcinoma cancer treated by laparoscopic hysterectomy at our institution, many of whom were high-risk for surgery.

Methods

Data was collected by a retrospective search of the case notes and Electronic Patient Records of the thirty eight patients who underwent laparoscopic hysterectomy for endometrial cancer at our institutions.

Results

The median body mass index was 30 (range 19–67). Comorbidities were present in 76% (29 patients); 40% (15 patients) had a single comorbid condition, whilst 18% (7 patients) had two, and a further 18% (7 patients) had more than two. Lymphadenectomy was performed in 45% (17 patients), and lymph node sampling in 21% (8 patients). Median operating time was 210 minutes (range 70–360 minutes). Median estimated blood loss was 200 ml (range 50–1000 ml). There were no intraoperative complications. Post-operative complications were seen in 21% (2 major, 6 minor). Blood transfusion was required in 5% (2 patients). The median stay was 4 post-operative nights (range 1–25 nights). In those patients undergoing lymphadenectomy, the mean number of nodes taken was fifteen (range 8–26 nodes). The pathological staging was FIGO stage I 76% (29 patients), stage II 8% (3 patients), stage III 16% (6 patients). The pathological grade was G1 31% (16 patients), G2 45% (17 patients), G3 24% (8 patients).

Conclusion

Laparoscopic hysterectomy can be safely carried out in patients at high risk for surgery, with no compromise in terms of outcomes, whilst providing all the benefits inherent in minimal access surgery.

     

Unexpected photobleaching of Alexa 488 in a fixed bacterial sample during 2-photon excitation

A sample of fixed bacterial cells was examined by immunofluorescence microscopy using an Alexa 488 conjugated secondary antibody for visualization. Excitation using visible light confirmed the expected photostability of this fluorophore; however, when using 2-photon excitation, Alexa 488 was rapidly and substantially photobleached. The unexpected instability of Alexa 488 under certain conditions may have deleterious consequences if not anticipated and accommodated in experimental protocols.     

Rhodnius prolixus and Rhodnius robustus–like (Hemiptera, Reduviidae) wing asymmetry under controlled conditions of population density and feeding frequency

Habitat change in Rhodnius spp may represent an environmental challenge for the development of the species, particularly when feeding frequency and population density vary in nature. To estimate the effect of these variables in stability on development, the degree of directional asymmetry (DA) and fluctuating asymmetry (FA) in the wing size and shape of R. prolixus and R. robustus–like were measured under laboratory controlled conditions. DA and FA in wing size and shape were significant in both species, but their variation patterns showed both inter-specific and sexual dimorphic differences in FA of wing size and shape induced by nutrition stress. These results suggest different abilities of the genotypes and sexes of two sylvatic and domestic genotypes of Rhodnius to buffer these stress conditions. However, both species showed non-significant differences in the levels of FA between treatments that simulated sylvan vs domestic conditions, indicating that the developmental noise did not explain the variation in wing size and shape found in previous studies. Thus, this result confirm that the variation in wing size and shape in response to treatments constitute a plastic response of these genotypes to population density and feeding frequency.     

Macrocyclic bisindolylmaleimides as inhibitors of protein kinase C and glycogen synthase kinase-3

Efficient methods were developed to synthesize a novel series of macrocyclic bisindolylmaleimides containing linkers with multiple heteroatoms. Potent inhibitors (single digit nanomolar IC(50)) for PKC-beta and GSK-3beta were identified, and compounds showed good selectivity over PKC-alpha, -gamma, -delta, -epsilon, and -zeta. Representative compound 5a also had high selectivity in a screening panel of 10 other protein kinases. In cell-based functional assays, several compounds effectively blocked interleukin-8 release induced by PKC-betaII and increased glycogen synthase activity by inhibiting GSK-3beta.