Clinical,socio‐demographic and psychological characteristics in individuals with persistent psychotic experiences with and without a “need for care”

Individuals reporting persistent psychotic experiences (PEs) in the general population, but without a “need for care”, are a unique group of particular importance in identifying risk and protective factors for psychosis. We compared people with persistent PEs and no “need for care” (non‐clinical, N=92) with patients diagnosed with a psychotic disorder (clinical, N=84) and controls without PEs (N=83), in terms of their phenomenological, socio‐demographic and psychological features. The 259 participants were recruited from one urban and one rural area in the UK, as part of the UNIQUE (Unusual Experiences Enquiry) study. Results showed that the non‐clinical group experienced hallucinations in all modalities as well as first‐rank symptoms, with an earlier age of onset than in the clinical group. Somatic/tactile hallucinations were more frequent than in the clinical group, while commenting and conversing voices were rare. Participants in the non‐clinical group were differentiated from their clinical counterparts by being less paranoid and deluded, apart from ideas of reference, and having fewer cognitive difficulties and negative symptoms. Unlike the clinical group, they were characterized neither by low psychosocial functioning nor by social adversity. However, childhood trauma featured in both groups. They were similar to the controls in psychological characteristics: they did not report current emotional problems, had intact self‐esteem, displayed healthy schemas about the self and others, showed high life satisfaction and well‐being, and high mindfulness. These findings support biopsychosocial models postulating that environmental and psychological factors interact with biological processes in the aetiology of psychosis. While some PEs may be more malign than others, lower levels of social and environmental adversity, combined with protective factors such as intact IQ, spirituality, and psychological and emotional well‐being, may reduce the likelihood of persistent PEs leading to pathological outcomes. Future research should focus on protective factors and determinants of well‐being in the context of PEs, rather than exclusively on risk factors and biomarkers of disease states.     

STUDIES ON ENZYME ACTION : XVIII. THE SACCHAROGENIC ACTIONS OF POTATO JUICE.

The saccharogenic enzymes present in potato juice were studied. The actions were followed upon the substances present in the juice and upon added sucrose, maltose, and soluble starch. Sucrase and amylase were found to be present in the juice. No indication of a maltase was obtained. The sucrase showed optimum conditions for action at pH 4 to 5, the amylase at pH 6 to 7, both upon the starch present in the juice and upon added soluble starch. The action of a yeast sucrase preparation upon the juice showed the presence of sucrose (or raffinose) in a concentration of the order of magnitude of 1 per cent.     

Formulation of entomopathogenic nematode-infected cadavers

Entomopathogenic nematodes are commercially applied in aqueous suspension. These biocontrol agents may also be applied in nematode-infected insect cadavers, but this approach may entail problems in storage and ease of handling. We determined the feasibility of formulating nematode-infected insect cadavers to overcome these hindrances. All experiments were conducted with Heterorhabditis bacteriophora Poinar and Galleria mellonella (L.). Nonformulated cadavers were used as controls. Of 19 formulations tested (including combinations of starches, flours, clays, etc.) 1 (starch-clay combination) was found to adhere to the cadaver and to have no significant deleterious effects on nematode reproduction and infectivity; other formulations exhibited poor adhesion or reduced nematode reproduction. Two formulations enabled cadavers to be partially desiccated without affecting reproduction; other formulations and nonformulated cadavers exhibited reduced reproduction upon desiccation. Four-day-old cadavers were more amenable to desiccation than 8-day-old cadavers. Formulated cadavers were more resistant to rupturing and sticking together during agitation than nonformulated cadavers.     

Deletion mapping of homoeologous group 6-specific wheat expressed sequence tags

To localize wheat (Triticum aestivum L.) ESTs on chromosomes, 882 homoeologous group 6-specific ESTs were identified by physically mapping 7965 singletons from 37 cDNA libraries on 146 chromosome, arm, and sub-arm aneuploid and deletion stocks. The 882 ESTs were physically mapped to 25 regions (bins) flanked by 23 deletion breakpoints. Of the 5154 restriction fragments detected by 882 ESTs, 2043 (loci) were localized to group 6 chromosomes and 806 were mapped on other chromosome groups. The number of loci mapped was greatest on chromosome 6B and least on 6D. The 264 ESTs that detected orthologous loci on all three homoeologs using one restriction enzyme were used to construct a consensus physical map. The physical distribution of ESTs was uneven on chromosomes with a tendency toward higher densities in the distal halves of chromosome arms. About 43% of the wheat group 6 ESTs identified rice homologs upon comparisons of genome sequences. Fifty-eight percent of these ESTs were present on rice chromosome 2 and the remaining were on other rice chromosomes. Even within the group 6 bins, rice chromosomal blocks identified by 1-6 wheat ESTs were homologous to up to 11 rice chromosomes. These rice-block contigs were used to resolve the order of wheat ESTs within each bin.     

Dual mycorrhizal colonization of forest-dominating tropical trees and the mycorrhizal status of non-dominant tree and liana species

The contribution of mycorrhizal associations to maintaining tree diversity patterns in tropical rain forests is poorly known. Many tropical monodominant trees form ectomycorrhizal (EM) associations, and there is evidence that the EM mutualism contributes to the maintenance of monodominance. It is assumed that most other tropical tree species form arbuscular mycorrhizal (AM) associations, and while many mycorrhizal surveys have been done, the mycorrhizal status of numerous tropical tree taxa remains undocumented. In this study, we tested the assumption that most tropical trees form AM associations by sampling root vouchers from tree and liana species in monodominant Dicymbe corymbosa forest and an adjacent mixed rain forest in Guyana. Roots were assessed for the presence/absence of AM and EM structures. Of the 142 species of trees and lianas surveyed, three tree species (the monodominant D. corymbosa, the grove-forming D. altsonii, and the non-dominant Aldina insignis) were EM, 137 were exclusively AM, and two were non-mycorrhizal. Both EM and AM structures were observed in D. corymbosa and D. altsonii. These results provide empirical data supporting the assumption that most tropical trees form AM associations for this region in the Guiana Shield and provide the first report of dual EM/AM colonization in Dicymbe species. Dual colonization of the Dicymbe species should be further explored to determine if this ability contributes to the establishment and maintenance of site dominance. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

A Liposomal Drug Platform Overrides Peptide Ligand Targeting to a Cancer Biomarker,Irrespective of Ligand Affinity or Density

One method for improving cancer treatment is the use of nanoparticle drugs functionalized with targeting ligands that recognize receptors expressed selectively by tumor cells. In theory such targeting ligands should specifically deliver the nanoparticle drug to the tumor, increasing drug concentration in the tumor and delivering the drug to its site of action within the tumor tissue. However, the leaky vasculature of tumors combined with a poor lymphatic system allows the passive accumulation, and subsequent retention, of nanosized materials in tumors. Furthermore, a large nanoparticle size may impede tumor penetration. As such, the role of active targeting in nanoparticle delivery is controversial, and it is difficult to predict how a targeted nanoparticle drug will behave in vivo. Here we report in vivo studies for α_vβ₆-specific H2009.1 peptide targeted liposomal doxorubicin, which increased liposomal delivery and toxicity to lung cancer cells in vitro. We systematically varied ligand affinity, ligand density, ligand stability, liposome dosage, and tumor models to assess the role of active targeting of liposomes to α_vβ₆. In direct contrast to the in vitro results, we demonstrate no difference in in vivo targeting or efficacy for H2009.1 tetrameric peptide liposomal doxorubicin, compared to control peptide and no peptide liposomes. Examining liposome accumulation and distribution within the tumor demonstrates that the liposome, and not the H2009.1 peptide, drives tumor accumulation, and that both targeted H2009.1 and untargeted liposomes remain in perivascular regions, with little tumor penetration. Thus H2009.1 targeted liposomes fail to improve drug efficacy because the liposome drug platform prevents the H2009.1 peptide from both actively targeting the tumor and binding to tumor cells throughout the tumor tissue. Therefore, using a high affinity and high specificity ligand targeting an over-expressed tumor biomarker does not guarantee enhanced efficacy of a liposomal drug. These results highlight the complexity of in vivo targeting.     

Preclinical Assessment of Adjunctive tPA and DNase for Peritoneal Dialysis Associated Peritonitis

A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis.     

Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels

Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block showed fast and slow phases, in contrast to the single phase found for amantadine block of wild-type M2. Here, we evaluate the mechanism of block by copper adamantyl iminodiacitate and copper cyclooctyl iminodiacitate complexes and address whether the complexes can coordinate with one or more of the His37 imidazoles. The current traces were fitted to parametrized master equations. The energetics of binding and the rate constants suggest that the first step is copper complex binding within the channel, and the slow step in the current block is the formation of a Cu-histidine coordination complex. Solution-phase isothermal titration calorimetry and density functional theory (DFT) calculations indicate that imidazole binds to the copper complexes. Structural optimization using DFT reveals that the complexes fit inside the channel and project the Cu(II) toward the His37 cluster, allowing one imidazole to form a coordination complex with Cu(II). Electrophysiology and DFT studies also show that the complexes block the G34E amantadine-resistant mutant despite some crowding in the binding site by the glutamates.