The Effect of Simulating Different Intermediate Host Snail Species on the Link between Water Temperature and Schistosomiasis Risk

Introduction

A number of studies have attempted to predict the effects of climate change on schistosomiasis risk. The importance of considering different species of intermediate host snails separately has never previously been explored.

Methods

An agent-based model of water temperature and Biomphalaria pfeifferi population dynamics and Schistosoma mansoni transmission was parameterised to two additional species of snail: B. glabrata and B. alexandrina.

Results

Simulated B. alexandrina populations had lower minimum and maximum temperatures for survival than B. pfeifferi populations (12.5–29.5°C vs. 14.0–31.5°C). B. glabrata populations survived over a smaller range of temperatures than either B. pfeifferi or B. alexandrina (17.0°C–29.5°C). Infection risk peaked at 16.5°C, 25.0°C and 19.0°C respectively when B. pfeifferi, B. glabrata and B. alexandrina were simulated. For all species, infection risk increased sharply once a minimum temperature was reached.

Conclusions

The results from all three species suggest that infection risk may increase dramatically with small increases in temperature in areas at or near the currents limits of schistosome transmission. The effect of small increases in temperature in areas where schistosomiasis is currently found will depend both on current temperatures and on the species of snail acting as intermediate host(s) in the area. In most areas where B. pfeifferi is the host, infection risk is likely to decrease. In cooler areas where B. glabrata is the host, infection risk may increase slightly. In cooler areas where B. alexandrina is the host, infection risk may more than double with only 2°C increase in temperature. Our results show that it is crucial to consider the species of intermediate host when attempting to predict the effects of climate change on schistosomiasis.     

Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease

Introduction

The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans.

Methods

RA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the weighted risk-allele counts.

Results

After genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF) were tightly correlated between Cameroonian controls and YRI individuals (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456). Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001.

Conclusions

The MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in West/Central Africa. The genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility SNPs is significantly different between the UK and Africa with p<0.001. Taken together, these observations strengthen the hypothesis that the genetic architecture of RA susceptibility is different in different ethnic backgrounds.     

Using historical ecology to understand patterns of biodiversity in fragmented agricultural landscapes

Aim To enhance current attempts to understand biodiversity patterns by using an historical ecology approach to highlight the over‐riding influence of land‐use history in creating past, current and future patterns of biodiversity in fragmented agricultural landscapes. Methods We develop an integrative conceptual framework for understanding spatial and temporal variations in landscape patterns in fragmented agricultural landscapes by presenting five postulates (hypotheses) which highlight the important role of historical, anthropogenic disturbance regimes. We then illustrate each of these postulates with examples drawn from fragmented woodlands in agricultural areas of south‐eastern Australia, and discuss these findings in an international context. Location examples are drawn from agricultural areas in south‐eastern Australia. Results We conclude that there is limited potential to refine our understanding of patterns of biodiversity in human‐modified landscapes based on traditional concepts of island biogeography, or simple assumptions of ongoing destruction and degradation. Instead, we propose that in agricultural landscapes that were largely cleared over a century ago: (1) present‐day remnant vegetation patterns are not accidental, but are logically arrayed due to historic land‐use decisions, (2) historic anthropogenic disturbances have a major influence on current ecosystem conditions and diversity patterns, and (3) the condition of remnant ecosystems is not necessarily deteriorating rapidly. Main conclusions An historical ecology approach can enhance our understanding of why different species and ecosystem states occur where they do, and can explain internal variations in ecological conditions within remnant ecosystems, too often casually attributed to the ‘mess of history’. This framework emphasizes temporal changes (both past and future) in biotic patterns and processes in fragmented agricultural landscapes. Integration of spatially and temporally explicit historical land‐use information into ecological studies can prove extremely useful to test hypotheses of the effects of changes in landscape processes, and to enhance future research, restoration and conservation management activities.     

Development of a neuronal pressure sensor

Neuronal sensory systems are capable of performing very complex signal processing functions. Reconstruction of such sensory systems in vitro should enable whole-cell biological sensors to be generated that possess inherent signal processing capabilities. In this paper, the results of preliminary investigations to produce a mechanosensory neuronal network are presented. An in vitro network of rat dorsal root ganglion neurons has been produced on a microelectrode plate revealing an interesting rhythmical pattern of spontaneous discharges. This periodic activity has been shown to be disrupted following the application of a static pressure to the cell culture. These results indicate that neuronal networks represent a practical system that may be used for the development of intelligent, whole-cell, biological sensors.     

Terminal care: present services and future priorities.

Since 1975 hospices and other specialist services for terminal cancer have expanded rapidly. In December 1980 this survey found 72 such services in Britain providing 58 inpatient units, 32 home care teams, and eight hospital support teams. Many were outside the NHS. Inpatient units provided 1297 beds (modal size 21-25 beds) and dealt with under 7% of deaths from cancer. Home care teams provided 76.5 full-time equivalent nurses (modal size two nurses). Regional variations were considerable: from 10.9 beds/million population in Trent to 48.5 beds/million in South-west Thames; no home care nurses in Mersey and Wales, and 5.1 nurses/million in Wessex. Of 58 more services being planned, the 17 starting in 1981 will not substantially alter these regional imbalances. Respondents'' opinions suggest a target of 40-50 inpatient unit beds/million population. This might be reduced if hospitals were better equipped to deal with these patients. Suggested priorities are to redress regional inequalities, develop home care and hospital support teams rather than inpatient units, and improve teaching and training. Co-ordination of plans between the NHS and the voluntary sector is needed.     

Rhamnolipids modulate swarming motility patterns of Pseudomonas aeruginosa

Pseudomonas aeruginosa is capable of twitching, swimming, and swarming motility. The latter form of translocation occurs on semisolid surfaces, requires functional flagella and biosurfactant production, and results in complex motility patterns. From the point of inoculation, bacteria migrate as defined groups, referred to as tendrils, moving in a coordinated manner capable of sensing and responding to other groups of cells. We were able to show that P. aeruginosa produces extracellular factors capable of modulating tendril movement, and genetic analysis revealed that modulation of these movements was dependent on rhamnolipid biosynthesis. An rhlB mutant (deficient in mono- and dirhamnolipid production) and an rhlC mutant (deficient in dirhamnolipid production) exhibited altered swarming patterns characterized by irregularly shaped tendrils. In addition, agar supplemented with rhamnolipid-containing spent supernatant inhibited wild-type (WT) swarming, whereas agar supplemented with spent supernatant from mutants that do not make rhamnolipids had no effect on WT P. aeruginosa swarming. Addition of purified rhamnolipids to swarming medium also inhibited swarming motility of the WT strain. We also show that a sadB mutant does not sense and/or respond to other groups of swarming cells and this mutant was capable of swarming on media supplemented with rhamnolipid-containing spent supernatant or purified rhamnolipids. The abilities to produce and respond to rhamnolipids in the context of group behavior are discussed.     

Acute pH-dependent regulation of AE2-mediated anion exchange involves discrete local surfaces of the NH2-terminal cytoplasmic domain

We have previously defined in the NH2-terminal cytoplasmic domain of the mouse AE2/SLC4A2 anion exchanger a critical role for the highly conserved amino acids (aa) 336-347 in determining wild-type pH sensitivity of anion transport. We have now engineered hexa-Ala ((A)6) and individual amino acid substitutions to investigate the importance to pH-dependent regulation of AE2 activity of the larger surrounding region of aa 312-578. 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive 36Cl- efflux from AE2-expressing Xenopus oocytes was monitored during changes in pHi or pHo in HEPES-buffered and in 5% CO2/HCO3- -buffered conditions. Wild-type AE2-mediated 36Cl- efflux was profoundly inhibited at low pHo, with a pHo(50) value = 6.75 +/- 0.05 and was stimulated up to 10-fold by intracellular alkalinization. Individual mutation of several amino acid residues at non-contiguous sites preceding or following the conserved sequence aa 336-347 attenuated pHi and/or pHo sensitivity of 36Cl- efflux. The largest attenuation of pH sensitivity occurred with the AE2 mutant (A)6357-362. This effect was phenocopied by AE2 H360E, suggesting a crucial role for His360. Homology modeling of the three-dimensional structure of the AE2 NH2-terminal cytoplasmic domain (based on the structure of the corresponding region of human AE1) predicts that those residues shown by mutagenesis to be functionally important define at least one localized surface region necessary for regulation of AE2 activity by pH.     

Characterising the micro-mechanical behaviour of the carious dentine of primary teeth using nano-indentation

A better appreciation of the properties of carious dentine would be of clinical advantage in carious assessment and management. The aim of this study is to understand the deterioration of the mechanical properties of carious dentine as a result of bacterial demineralising process as well as change in dentine structures observed under scanning electronic microscope. Eight primary molar teeth with untreated carious dentine were axially sectioned and fine polished for nano-indentation. On each specimen, six lines of indentation, evenly distributed through the lesion, were made from the pulp to lesion cavity floor parallel to tubule direction using nano-indentation (Ultra Micro Indentation System, UMIS-2000), while another two indentation lines were made on an adjacent region of sound dentine in the same manner. All tests were conducted on hydrated specimens. Hardness and elastic modulus decreased significantly and progressively toward the cavity floor varying from 0.56 to 0.001 GPa and 14.55 to 0.015 GPa, respectively. The change in mechanical properties was in a specific pattern as a function of lesion depth, in which the hardness could be fitted to an exponential function, while the variation of the elastic modulus across the entire lesion was fitted to a power law relationship. More critical evaluation of the elastic modulus data indicated that two distinct exponential functions provided an excellent fit to the results. These changes in elastic modulus also matched the structural changes seen across a lesion, which were associated with a change from primarily peritubular to intertubular dissolution.