The Genetic Basis of Host Preference and Resting Behavior in the Major African Malaria Vector,Anopheles arabiensis

Malaria transmission is dependent on the propensity of Anopheles mosquitoes to bite humans (anthropophily) instead of other dead end hosts. Recent increases in the usage of Long Lasting Insecticide Treated Nets (LLINs) in Africa have been associated with reductions in highly anthropophilic and endophilic vectors such as Anopheles gambiae s.s., leaving species with a broader host range, such as Anopheles arabiensis, as the most prominent remaining source of transmission in many settings. An. arabiensis appears to be more of a generalist in terms of its host choice and resting behavior, which may be due to phenotypic plasticity and/or segregating allelic variation. To investigate the genetic basis of host choice and resting behavior in An. arabiensis we sequenced the genomes of 23 human-fed and 25 cattle-fed mosquitoes collected both in-doors and out-doors in the Kilombero Valley, Tanzania. We identified a total of 4,820,851 SNPs, which were used to conduct the first genome-wide estimates of “SNP heritability” for host choice and resting behavior in this species. A genetic component was detected for host choice (human vs cow fed; permuted P = 0.002), but there was no evidence of a genetic component for resting behavior (indoors versus outside; permuted P = 0.465). A principal component analysis (PCA) segregated individuals based on genomic variation into three groups which were characterized by differences at the 2Rb and/or 3Ra paracentromeric chromosome inversions. There was a non-random distribution of cattle-fed mosquitoes between the PCA clusters, suggesting that alleles linked to the 2Rb and/or 3Ra inversions may influence host choice. Using a novel inversion genotyping assay, we detected a significant enrichment of the standard arrangement (non-inverted) of 3Ra among cattle-fed mosquitoes (N = 129) versus all non-cattle-fed individuals (N = 234; χ², p = 0.007). Thus, tracking the frequency of the 3Ra in An. arabiensis populations may be of use to infer selection on host choice behavior within these vector populations; possibly in response to vector control. Controlled host-choice assays are needed to discern whether the observed genetic component has a direct relationship with innate host preference. A better understanding of the genetic basis for host feeding behavior in An. arabiensis may also open avenues for novel vector control strategies based on driving genes for zoophily into wild mosquito populations.     

A comparison of acylation, phosphorylation and binding in related substrates and inhibitors of serum cholinesterase

1. The K_m and catalytic-centre activities for human serum cholinesterase and methyl, ethyl, n-propyl and n-butyl butyrate substrates were determined and compared with the related inhibition constants of a similarly substituted organophosphate inhibitor series based on malaoxon. The results indicated that the catalytic-centre activities approximated to k_+2(a), the acylation rate constant, and that K_m approximated to the equilibrium binding constant. The inhibition constants measured were K_a, the equilibrium binding constant, and k_+2(p), the phosphorylation rate constant. 2. The effects of the alkyl substituents on k_+2(p) and k_+2(a) were closely parallel, and the decreasing order in each case was: n-butyl; methyl; n-propyl; ethyl. The Taft constants did not follow this order, suggesting that alkyl substituents did not primarily effect acylation or phosphorylation by electron induction. 3. For comparable homologues, the k_+2(a) values were on average 435 times the k_+2(p) values. The k_+2(p) values at 25° and pH7·6 ranged from 6·6min.⁻¹ for the diethyl member to 22·6min.⁻¹ for the di-n-butyl member. 4. The effect of the alkyl substituents on K_a and K_m were closely paralleled. The increasing order in each case was: n-butyl; n-propyl; ethyl; methyl. The K_a values were about 100 times less than the comparable K_m values. 5. Consideration of the binding energies suggested that only one of the two alkyl groups on the malaoxon homologues bound to the active site. 6. The possibility that malaoxon acted as a substrate as well as an inhibitor for cholinesterase was also investigated, but no evidence of a substrate reaction was found.     

Tick-borne Kemerovo group orbiviruses in a Newfoundland seabird colony

Five new isolates of Kemerovo group viruses were recovered from Ixodes uriae collected on Great Island, Witless Bay Seabird Sanctuary, Newfoundland, Canada, during July 1985. This brings the total number of Orbivirus isolates on Great Island to 18 isolates including the 7 from 1971 and 6 from 1972. Genomic segments of several strains were compared by polyacrylamide gel electrophoresis. The degree of variation in each segment of these viruses was calculated. Great Island and Bauline viruses exhibited a great degree of variation in dsRNA migration patterns. Great Island and Bauline genomes averaged 11.60 (SD = 0.107) and 11.69 megadaltons (SD = 0.075), respectively. Variation was observed in all 10 segments of Great Island and Bauline viruses. These findings were compared with serologic and protein gel data.     

Symptoms and signs: physical disease or illness behaviour?

The amount of treatment received by 380 patients with backache was found to have been influenced more by their distress and illness behaviour than by the actual physical disease. Patients showing a large amount of inappropriate illness behaviour had received significantly more treatment (p less than 0.001). The symptoms and signs of illness behaviour need to be clearly distinguished from those of physical disease, and better assessment of illness behaviour is essential if everyday clinical practice is to fulfil the ideal of treating patients as well as diseases.     

Sex-dimorphic moderate hypoglycemia preconditioning effects on Hippocampal CA1 neuron bio-energetic and anti-oxidant function

Molecular and Cellular Biochemistry - Hypoglycemia is a detrimental complication of rigorous management of type 1 diabetes mellitus. Moderate hypoglycemia (MH) preconditioning of male rats...     

Management of chronic hepatitis C: clinical audit of biopsy based management algorithm.

OBJECTIVE: To assess the attendance, outcome, compliance with treatment, and response to interferon alfa in patients with chronic hepatitis C who attended during 1995 and were treated according to a biopsy based algorithm. DESIGN: Retrospective audit of all patients with chronic hepatitis C attending outpatient clinics over one year. SETTING: The liver unit at a London teaching hospital. SUBJECTS: 255 patients with chronic hepatitis C. MAIN OUTCOME MEASURES: Patient survival, attendance, and compliance with diagnostic and therapeutic regimens. Response to interferon alfa treatment, based on loss of viraemia three months after cessation of treatment. RESULTS: A large proportion of patients (39%) with newly diagnosed chronic hepatitis C infection do not want to undergo further investigation. Of those patients who do attend for further treatment, a large proportion with severe hepatic fibrosis (42%) do not want to undergo currently available treatment. The response rate to interferon (21%) in treated patients was similar to that previously reported in a trial setting. There was no significant difference in response rates in patients with or without severe fibrosis not amounting to cirrhosis. In patients with cirrhosis there was a high incidence of hepatocellular carcinoma (18%) over a follow up period of 20 months. CONCLUSION: Current strategies aimed at investigating and treating patients with chronic hepatitis C are not acceptable to a large proportion of patients. Many patients with cirrhosis related to hepatitis C infection develop hepatic neoplasms, and management strategies to deal with this problem are urgently required.