Hepatitis C Virus Phylogenetic Clustering Is Associated with the Social-Injecting Network in a Cohort of People Who Inject Drugs

It is hypothesized that social networks facilitate transmission of the hepatitis C virus (HCV). We tested for association between HCV phylogeny and reported injecting relationships using longitudinal data from a social network design study. People who inject drugs were recruited from street drug markets in Melbourne, Australia. Interviews and blood tests took place three monthly (during 2005–2008), with participants asked to nominate up to five injecting partners at each interview. The HCV core region of individual isolates was then sequenced and phylogenetic trees were constructed. Genetic clusters were identified using bootstrapping (cut-off: 70%). An adjusted Jaccard similarity coefficient was used to measure the association between the reported injecting relationships and relationships defined by clustering in the phylogenetic analysis (statistical significance assessed using the quadratic assignment procedure). 402 participants consented to participate; 244 HCV infections were observed in 238 individuals. 26 genetic clusters were identified, with 2–7 infections per cluster. Newly acquired infection (AOR = 2.03, 95% CI: 1.04–3.96, p = 0.037, and HCV genotype 3 (vs. genotype 1, AOR = 2.72, 95% CI: 1.48–4.99) were independent predictors of being in a cluster. 54% of participants whose infections were part of a cluster in the phylogenetic analysis reported injecting with at least one other participant in that cluster during the study. Overall, 16% of participants who were infected at study entry and 40% of participants with newly acquired infections had molecular evidence of related infections with at least one injecting partner. Likely transmission clusters identified in phylogenetic analysis correlated with reported injecting relationships (adjusted Jaccard coefficient: 0.300; p<0.001). This is the first study to show that HCV phylogeny is associated with the injecting network, highlighting the importance of the injecting network in HCV transmission.     

Robot-Mediated Interviews - How Effective Is a Humanoid Robot as a Tool for Interviewing Young Children?

Robots have been used in a variety of education, therapy or entertainment contexts. This paper introduces the novel application of using humanoid robots for robot-mediated interviews. An experimental study examines how children’s responses towards the humanoid robot KASPAR in an interview context differ in comparison to their interaction with a human in a similar setting. Twenty-one children aged between 7 and 9 took part in this study. Each child participated in two interviews, one with an adult and one with a humanoid robot. Measures include the behavioural coding of the children’s behaviour during the interviews and questionnaire data. The questions in these interviews focused on a special event that had recently taken place in the school. The results reveal that the children interacted with KASPAR very similar to how they interacted with a human interviewer. The quantitative behaviour analysis reveal that the most notable difference between the interviews with KASPAR and the human were the duration of the interviews, the eye gaze directed towards the different interviewers, and the response time of the interviewers. These results are discussed in light of future work towards developing KASPAR as an ‘interviewer’ for young children in application areas where a robot may have advantages over a human interviewer, e.g. in police, social services, or healthcare applications.     

Direct Synthesis of Pyrrole Nucleosides by the Stereospecific Sodium Salt Glycosylation Procedure

Abstract

A number of 1-β-D-arabinofuranosyl and l-(2-deoxy-β-D-erythro-pentofuranosyl) derivatives of substituted pyrroles have been prepared in good yields by the direct glycosylation of the sodium salt of a preformed fully aromatic pyrrole with an appropriate α-halogenose.     

Effect of different molecular species of phosphatidylcholine on the clearance of emulsion particle lipids

Studies were performed to assess the effect of changes in the molecular species composition of phosphatidylcholine (PC) on the clearance of emulsion particles that were made to approximate chylomicrons in size and lipid composition. Emulsions were prepared with free [14C]cholesterol, [3H]cholesteryl oleate, triolein, and one of four single PCs that differed in hydrophilic strength (as assessed by the relative rate of elution of these PCs from a reverse phase column). Emulsions were injected as an intravenous bolus into unanesthetized rats and the clearance of lipids was determined at 2-min intervals for 10 min. All emulsion lipids were cleared from the serum in parallel and in an order that closely corresponded to the relative hydrophilic strength of the particular PC that was administered. Fractional rates of clearance, calculated from log-linear plots, were 2- to 10-fold greater for all lipids for the emulsion that was made with the most hydrophilic PC compared to the least hydrophilic PC. Although hepatectomy, performed in acutely anesthetized animals, generally slowed the clearance of lipids, hepatectomy did not abolish differences in the clearance of triolein or specific PCs from emulsions prepared with the most and least hydrophilic PCs. These results indicate that a change in the composition of emulsion particle PCs, independent of any other change in the lipid composition of these particles, can significantly change the metabolism of the whole emulsion particle in the live animal. More specifically, these studies show that the rate of clearance of all emulsion lipids closely corresponds to the hydrophilic strength of the PCs that occupy the emulsion particle surface.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of DNA metabolic enzymes upon induction of preB cell development and V(D)J recombination: up-regulation of DNA polymerase delta.

Withdrawal of interleukin-7 from cultured murine preB lymphocytes induces cell differentiation including V(D)J immunoglobulin gene rearrangements and cell cycle arrest. Advanced steps of the V(D)J recombination reaction involve processing of coding ends by several largely unidentified DNA metabolic enzymes. We have analyzed expression and activity of DNA polymerases alpha, beta, delta and epsilon, proliferating cell nuclear antigen (PCNA), topoisomerases I and II, terminal deoxynucleotidyl transferase (TdT) and DNA ligases I, III and IV upon induction of preB cell differentiation. Despite the immediate arrest of cell proliferation, DNA polymerase delta protein levels remained unchanged for approximately 2 days and its activity was up-regulated several-fold, while PCNA was continuously present. Activity of DNA polymerases alpha,beta and epsilon decreased. Expression and activity of DNA ligase I were drastically reduced, while those of DNA ligases III and IV remained virtually constant. No changes in DNA topoisomerases I or II expression and activity occurred and TdT expression was moderately increased early after induction. Our results render DNA polymerase delta a likely candidate acting in DNA synthesis related to V(D)J recombination in lymphocytes.     

Amiloride does not alter NaCl avoidance in Fischer-344 rats

Fischer-344 (F-344) rats differ from other common rat strains in that they fail to show any preference for NaCl at any concentration in two- bottle preference tests. Because 100 microM amiloride partially blocks the NaCl-evoked chorda tympani (CT) response in electrophysiological studies, we tested NaCl preference (0.068-0.273 M) in F-344 rats with and without 100 microM amiloride solution as the solvent. A third group was tested with unadulterated NaCl solutions following CT transection. Amiloride had no significant effect on the NaCl preference-aversion function, whereas CT transection significantly reduced NaCl avoidance. These results suggest that the amiloride-sensitive component of the NaCl response is not necessary for F-344 rats to display avoidance of NaCl, but the entire CT input is.      

A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein.

Mammalian DNA polymerases alpha and beta lack 3' exonuclease activity and are unable to edit errors after DNA synthesis. However, editing exonucleases can be functions of separate polypeptides. We isolated a widely distributed DNA-specific 3' exonuclease from rabbit liver nuclei, sequenced tryptic peptides by mass spectrometry, and identified the corresponding human open reading frame. The protein expressed from the cloned human sequence exhibits 3' exonuclease activity. The human clone shares sequence homology with the editing function of the Escherichia coli DNA polymerase III holoenzyme, i.e., the DnaQ/MutD protein, and weakly with the editing 3' exonuclease domain of eukaryotic DNA polymerase epsilon. The gene maps to human chromosome 3p21.2-21.3. In a reconstituted human DNA repair system containing DNA polymerase beta and DNA ligase III-XRCC1, accurate rejoining of a 3' mismatched base residue at a single-strand break is dependent on addition of the exonuclease.