Dissociating mere exposure and repetition priming as a function of word type

The mere exposure effect is defined as enhanced attitude toward a stimulus that has been repeatedly exposed. Repetition priming is defined as facilitated processing of a previously exposed stimulus. We conducted a direct comparison between the two phenomena to test the assumption that the mere exposure effect represents an example of repetition priming. In two experiments, having studied a set of words or nonwords, participants were given a repetition priming task (perceptual identification) or one of two mere exposure (affective liking or preference judgment) tasks. Repetition printing was obtained for both words and nonwords, but only nonwords produced a mere exposure effect. This demonstrates a key boundary for observing the mere exposure effect, one not readily accommodated by a perceptual representation systems (Tulving & Schacter, 1990) account, which assumes that both phenomena should show some sensitivity to nonwords and words.

Effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk: the RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial

Background: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain. Objective: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome. Design: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets. Results: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 × 10−4 mL · μU−1 · min−1 (interquartile range: 2.0, 4.2 × 10−4 mL · μU−1 · min−1), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, −4% (−12.7%, 5.3%); for the HM/HGI group, 2.1% (−5.8%, 10.7%); for the HM/LGI group, −3.5% (−10.6%, 4.3%); for the LF/HGI group, −8.6% (−15.4%, −1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations. Conclusions: This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

Development of peptide-conjugated morpholino oligomers as pan-arenavirus inhibitors

Members of the Arenaviridae are a threat to public health and can cause meningitis and hemorrhagic fever, yet treatment options remain limited by a lack of effective antivirals. In this study, we found that peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) complementary to viral genomic RNA were effective in reducing arenavirus replication in cell cultures and in vivo. PPMO complementary to the Junín virus genome were designed to interfere with viral RNA synthesis, translation, or both. However, only PPMO designed to potentially interfere with translation were effective in reducing virus replication. PPMO complementary to sequence that is highly conserved across arenaviruses and located at the 5’-termini of both genomic segments were effective against Junín, Tacaribe, Pichinde and Lymphocytic Choriomeningitis arenavirus-infected cell cultures, and suppressed viral titers in the livers of LCMV-infected mice. These results suggest that arenavirus 5’-genomic-termini represent promising targets for pan-arenavirus antiviral therapeutic development.

A hydrogen-1 nuclear magnetic resonance, mass spectral and extended Hückel study of some olefin complexes of rhodium(I) and iridium(I) and the crystal and molecular structure of η4-2,4-dimethylpenta-1,4-diene(η5-formylcyclopentadienyl)rhodium(I)

A 1H NMR study of monosubstituted η-cyclopentadienyl-rhodium(I) complexes of type LLRh(C5H4X) and -iridium(I) complexes of type L2Ir(C5H4X) (L = ethene, LL = 1,3- or 1,5-diolefin; X = C(C6H5)3, CHO, or COOCH3) has been carried out. For complexes of both metals in which the neutral ligand is ethene or a non-conjugated diolefin the NMR spectra of the cyclopentadienyl protons are unusual in that H(2), H(5) resonate to high field either at room temperature or below. The corresponding NMR spectra for the cyclopentadienyl ring protons of complexes where the neutral ligand is a conjugated diene are, with one exception, normal. A single crystal X-ray structural analysis of (η4-2,4-dimethylpenta-1,4-diene)(η5-formylcyclopentadienyl)rhodium(I) (which exhibits an abnormal 1H NMR spectrum) reveals substantial localisation of electron density in the C(3)C(4) Cp ring bond (1.283(33) Å) which may be consistent with a contribution from an ‘allyl-ene’ rotamer to the ring—metal bonding scheme. An extended Hückel calculation with self consistent charge iteration was performed on this complex. The results predict a greater Mulliken overlap population for the C(3)C(4) bond in the cyclopentadienyl ring and show that the localisation is dependent on both the Cp ring substituent and the nature of the diolefin. The mass spectral fragmentation patterns of some representative diene complexes of iridium(I) and rhodium(I) are presented.

Comparison of the rheology of mozzarella-type curd made from buffalo and cows’ milk

Curd rheology and calcium distribution in buffalo and cows’ milk, were compared at their natural pH and during acidification (pH 6.5–5.6). Buffalo milk displays a curd structure and rheology different from that of cows’ milk and the casein-bound calcium, as well as the contents of fat, protein and calcium, are also higher. Due to these higher amounts of casein-bound calcium, the overall curd strength with buffalo milk (as indicated by the dynamic moduli) was higher, at similar pH values, than those of equivalent gels produced from cows’ milk. The curd rheology was adversely affected at lower pH (5.8–5.6) in both of the milk types, due to the loss of casein-bound calcium from casein micelles. The degree of solubilisation of calcium in buffalo milk during acidification is quite different from that observed in cows’ milk with a lower proportion of the calcium being solubilised in the former. The maximum curd firmness was obtained at pH 6.0 in both milk types. For both species, these rheological and micellar changes were qualitatively the same but quantitatively different, due to the different milk compositions.

Effective elements of cognitive behaviour therapy for psychosis: results of a novel type of subgroup analysis based on principal stratification

Background. Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. Method. The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. Results. Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. Conclusions. Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.

Assessing bee species richness in two Mediterranean communities: importance of habitat type and sampling techniques

The decline of bees has raised concerns regarding their conservation and the maintenance of ecosystem services they provide to bee-pollinated wild flowers and crops. Although the Mediterranean region is a hotspot for bee species richness, their status remains poorly studied. There is an urgent need for cost-effective, reliable, and unbiased sampling methods that give good bee species richness estimates. This study aims: (a) to assess bee species richness in two common Mediterranean habitat types: semi-natural scrub (phrygana) and managed olive groves; (b) to compare species richness in those systems to that of other biogeographic regions, and (c) to assess whether six different sampling methods (pan traps, variable and standardized transect walks, observation plots and trap nests), previously tested in other European biogeographic regions, are suitable in Mediterranean communities. Eight study sites, four per habitat type, were selected on the island of Lesvos, Greece. The species richness observed was high compared to other habitat types worldwide for which comparable data exist. Pan traps collected the highest proportion of the total bee species richness across all methods at the scale of a study site. Variable and standardized transect walks detected the highest total richness over all eight study sites. Trap nests and observation plots detected only a limited fraction of the bee species richness. To assess the total bee species richness in bee diversity hotspots, such as the studied habitats, we suggest a combination of transect walks conducted by trained bee collectors and pan trap sampling

Fabula: type design

Originally a screen font for the Fabula project in 2004-5 redesigned for print for Collins publishers for their children's dictionary covers

How level and type of deafness affects user perception of multimedia video clips

Our research investigates the impact that hearing has on the perception of digital video clips, with and without captions, by discussing how hearing loss, captions and deafness type affects user QoP (Quality of Perception). QoP encompasses not only a user's satisfaction with the quality of a multimedia presentation, but also their ability to analyse, synthesise and assimilate informational content of multimedia . Results show that hearing has a significant effect on participants’ ability to assimilate information, independent of video type and use of captions. It is shown that captions do not necessarily provide deaf users with a ‘greater level of information’ from video, but cause a change in user QoP, depending on deafness type, which provides a ‘greater level of context of the video’. It is also shown that post-lingual mild and moderately deaf participants predict less accurately their level of information assimilation than post-lingual profoundly deaf participants, despite residual hearing. A positive correlation was identified between level of enjoyment (LOE) and self-predicted level of information assimilation (PIA), independent of hearing level or hearing type. When this is considered in a QoP quality framework, it puts into question how the user perceives certain factors, such as ‘informative’ and ‘quality’.

Genetic predisposition to type 2 diabetes is associated with impaired insulin secretion but does not modify insulin resistance or secretion in response to an intervention to lower dietary saturated fat

Genome-wide association studies have identified SNPs reproducibly associated with type 2 diabetes (T2D). We examined the effect of genetic predisposition to T2D on insulin sensitivity and secretion using detailed phenotyping in overweight individuals with no diagnosis of T2D. Furthermore, we investigated whether this genetic predisposition modifies the responses in beta-cell function and insulin sensitivity to a 24-week dietary intervention. We genotyped 25 T2D-associated SNPs in 377 white participants from the RISCK study. Participants underwent an IVGTT prior to and following a dietary intervention that aimed to lower saturated fat intake by replacement with monounsaturated fat or carbohydrate. We composed a genetic predisposition score (T2D-GPS) by summing the T2D risk-increasing alleles of the 25 SNPs and tested for association with insulin secretion and sensitivity at baseline, and with the change in response to the dietary intervention. At baseline, a higher T2D-GPS was associated with lower acute insulin secretion (AIRg 4% lower/risk allele, P = 0.006) and lower insulin secretion for a given level of insulin sensitivity, assessed by the disposition index (DI 5% lower/risk allele, P = 0.002), but not with insulin sensitivity (Si). T2D-GPS did not modify changes in insulin secretion, insulin sensitivity or the disposition index in response to the dietary interventions to lower saturated fat. Participants genetically predisposed to T2D have an impaired ability to compensate for peripheral insulin resistance with insulin secretion at baseline, but this does not modify the response to a reduction in dietary saturated fat through iso-energetic replacement with carbohydrate or monounsaturated fat.

Sustained polymeric delivery of gene silencing antisense ODNs, siRNA, DNAzymes and ribozymes: in vitro and in vivo studies

Small interfering RNA (siRNA), antisense oligonucleotides (ODNs), ribozymes and DNAzymes have emerged as sequence-specific inhibitors of gene expression that may have therapeutic potential in the treatment of a wide range of diseases. Due to their rapid degradation in vivo, the efficacy of naked gene silencing nucleic acids is relatively short lived. The entrapment of these nucleic acids within biodegradable sustained-release delivery systems may improve their stability and reduce the doses required for efficacy. In this study, we have evaluated the potential in vitro and in vivo use of biodegradable poly (d,l-lactide-co-glycolide) copolymer (PLGA) microspheres as sustained delivery devices for ODNs, ribozyme, siRNA and DNA enzymes. In addition, we investigated the release of ODN conjugates bearing 5′-end lipophilic groups. The in vitro sustained release profiles of microsphere-entrapped nucleic acids were dependent on variables such as the type of nucleic acid used, the nature of the lipophilic group, and whether the nucleic acid used was single or double stranded. For in vivo studies, whole body autoradiography was used to monitor the bio-distribution of either free tritium-labelled ODN or that entrapped within PLGA microspheres following subcutaneous administration in Balb-c mice. The majority of the radioactivity associated with free ODN was eliminated within 24 h whereas polymer-released ODN persisted in organs and at the site of administration even after seven days post-administration. Polymer microsphere released ODN exhibited a similar tissue and cellular tropism to the free ODN. Micro-autoradiography analyses of the liver and kidneys showed similar bio-distribution for polymer-released and free ODNs with the majority of radioactivity being concentrated in the proximal convoluted tubules of the kidney and in the Kupffer cells of the liver. These findings suggest that biodegradable PLGA microspheres offer a method for improving the in vivo sustained delivery of gene silencing nucleic acids, and hence are worthy of further investigation as delivery systems for these macromolecules.

Transcriptional regulators of the GAD acid stress island are carried by effector protein-encoding prophages and indirectly control type III secretion in enterohemorrhagic Escherichia coli O157:H7

P>Type III secretion (T3S) plays a pivotal role in the colonization of ruminant hosts by Enterohemorrhagic Escherichia coli (EHEC). The T3S system translocates effector proteins into host cells to promote bacterial attachment and persistence. The repertoire and variation in prophage regions underpins differences in the pathogenesis and epidemiology of EHEC strains. In this study, we have used a collection of deletions in cryptic prophages and EHEC O157 O-islands to screen for novel regulators of T3S. Using this approach we have identified a family of homologous AraC-like regulators that indirectly repress T3S. These prophage-encoded secretion regulator genes (psr) are found exclusively on prophages and are associated with effector loci and the T3S activating Pch family of regulators. Transcriptional profiling, mutagenesis and DNA binding studies were used to show that these regulators usurp the conserved GAD acid stress resistance system to regulate T3S by increasing the expression of GadE (YhiE) and YhiF and that this regulation follows attachment to bovine epithelial cells. We further demonstrate that PsrA and effectors encoded within cryptic prophage CP933-N are required for persistence in a ruminant model of colonization.

Persistence of a wild type Escherichia coli and its multiple antibiotic-resistant (MAR) derivatives in the abattoir and on chilled pig carcasses

The aim of this study was to evaluate the ability of an Escherichia coli with the multiple antibiotic resistance (MAR) phenotype to withstand the stresses of slaughter compared to an isogenic progenitor strain. A wild type E. coli isolate (345-2RifC) of porcine origin was used to derive 3 isogenic MAR mutants. Escherichia coli 345-2RifC and its MAR derivatives were inoculated into separate groups of pigs. Once colonisation was established, the pigs were slaughtered and persistence of the E. coli strains in the abattoir environment and on the pig carcasses was monitored and compared. No significant difference (P>0.05) was detected between the shedding of the different E. coli strains from the live pigs. Both the parent strain and its MAR derivatives persisted in the abattoir environment, however the parent strain was recovered from 6 of the 13 locations sampled while the MAR derivatives were recovered from 11 of 13 and the number of MAR E. coil recovered was 10-fold higher than the parent strain at half of the locations. The parent strain was not recovered from any of the 6 chilled carcasses whereas the MAR derivatives were recovered from 3 out of 5 (P<0.001). This study demonstrates that the expression of MAR in 345-2RifC increased its ability to survive the stresses of the slaughter and chilling processes. Therefore in E. coli, MAR can give a selective advantage, compared to non-MAR strains, for persistence on chilled carcasses thereby facilitating transit of these strains through the food chain. (C) 2010 Elsevier B.V. All rights reserved.

Mozzarella-type curd made from buffalo, cows’ and ultrafiltered cows’ milk. 1. Rheology and microstructure

Rennet-induced curd was made from both natural buffalo and cows’ milk, and ultrafiltered cows’ milk (cows’ milk was concentrated such that it had a chemical composition approximately equivalent to that of the buffalo milk). These milk samples were compared on the basis of their rheology, physicochemical characteristics and curd microstructure. The ionic and soluble calcium contents were found to be similar in all milk samples studied. The total and casein bound calcium were higher in concentrated cows’ milk than in standard cows’ milk. Both cows’ milk types were found to have lower total and casein bound calcium than the buffalo milk. This is probably due to concentration of the colloidal part of milk (casein), during the ultrafiltration (UF) process. The rennet coagulation time was similar in UF cows’ and buffalo milk while both were shorter when compared with that of the cows’ milk. The dynamic moduli (G′, G″) values were higher in both the buffalo and UF cows’ milk than in the cows’ milk after 90 min coagulation. The loss tangent, however, was found to be similar in both the UF cows’ and buffalo milk curds and was lower than that observed for the cows’ milk (0.42, 0.42 and 0.48, respectively). The frequency profile of each type of curd was recorded 90 min after the enzyme addition (0.1–10 Hz); all samples were found to be “weak” viscoelastic, frequency dependent gels. The yield stress was also measured 95 min after the enzyme addition, and a higher value was observed in buffalo milk curd when compared with other curd samples made from both the natural cows’ milk and the UF cows’ milk. The cryo-scanning electron and confocal laser scanning micrographs showed that curd structure appeared to be more “dense” and less porous in buffalo milk than cows’ milk even after concentration to equivalent levels of protein/total solids to those found in the buffalo milk.

The role of type 1 and curli fimbriae of Shiga toxin-producing Escherichia coli in adherence to abiotic surfaces

Biofilm formation on abiotic surfaces may provide a source of microbial contamination and may also enhance microbial environmental survival. The role of fimbrial expression by Shiga toxin-producing Escherichia coli (STEC) in biofilm formation is poorly understood. This study aimed to investigate the role of STEC type 1 and curli fimbriae in adhesion to and biofilm formation on abiotic surfaces. None of 13 O157:H7 isolates expressed either fimbrial type whereas 11 of 13 and 5 of 13 non-O157 STEC elaborated type 1 fimbriae and curli fimbriae, respectively. Mutants made by allelic exchange of a diarrhoeal non-O157 STEC isolate, O128:H2 (E41509), unable to elaborate type 1 and curli fimbriae were made for adherence and biofilm assays. Elaboration of type 1 fimbriae was necessary for the adhesion to abiotic surfaces whereas curliation was associated with both adherence and subsequent biofilm formation. STEC O157:H7 adhered to thermanox and glass but poorly to polystyrene. Additionally, STEC O157:H7 failed to form biofilms. These data indicate that certain STEC isolates are able to form biofilms and that the elaboration of curli fimbriae may enhance biofilm formation leading to possible long-term survival and a potential source of human infection.