Chronic Trichuris muris infection in C57BL/6 mice causes significant changes in most microbiota and metabolome:effects reversed by pathogen clearance

Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation

The role of CDC48 in the retro-translocation of non-ubiquitinated toxin substrates in plant cells

When the catalytic A subunits of the castor bean toxins ricin and Ricinus communis agglutinin (denoted as RTA and RCA A, respectively) are delivered into the endoplasmic reticulum (ER) of tobacco protoplasts, they become substrates for ER-associated protein degradation (ERAD). As such, these orphan polypeptides are retro-translocated to the cytosol, where a significant proportion of each protein is degraded by proteasomes. Here we begin to characterise the ERAD pathway in plant cells, showing that retro-translocation of these lysine-deficient glycoproteins requires the ATPase activity of cytosolic CDC48. Lysine polyubiquitination is not obligatory for this step. We also show that while RCA A is found in a mannose-untrimmed form prior to its retro-translocation, a significant proportion of newly synthesised RTA cycles via the Golgi and becomes modified by downstream glycosylation enzymes. Despite these differences, both proteins are similarly retro-translocated

Anti-pseudomonad Activity of Manuka Honey and Antibiotics in a Specialized ex vivo Model Simulating Cystic Fibrosis Lung Infection

Pseudomonas aeruginosa causes problematic chronic lung infections in those suffering from cystic fibrosis. This is due to its antimicrobial resistance mechanisms and its ability to form robust biofilm communities with increased antimicrobial tolerances. Using novel antimicrobials or repurposing current ones is required in order to overcome these problems. Manuka honey is a natural antimicrobial agent that has been used for many decades in the treatment of chronic surface wounds with great success, particularly those infected with P. aeruginosa. Here we aim to determine whether the antimicrobial activity of manuka honey could potentially be repurposed to inhibit pulmonary P. aeruginosa infections using two ex vivo models. P. aeruginosa isolates (n = 28) from an international panel were tested for their susceptibility to manuka honey and clinically relevant antibiotics (ciprofloxacin, ceftazidime, and tobramycin), alone and in combination, using conventional antimicrobial susceptibility testing (AST). To increase clinical applicability, two ex vivo porcine lung (EVPL) models (using alveolar and bronchiolar tissue) were used to determine the anti-biofilm effects of manuka honey alone and in combination with antibiotics. All P. aeruginosa isolates were susceptible to manuka honey, however, varying incidences of resistance were seen against antibiotics. The combination of sub-inhibitory manuka honey and antibiotics using conventional AST had no effect on activity against the majority of isolates tested. Using the two ex vivo models, 64% (w/v) manuka honey inhibited many of the isolates where abnormally high concentrations of antibiotics could not. Typically, combinations of both manuka honey and antibiotics had increased antimicrobial activity. These results highlight the potential of manuka honey as a future antimicrobial for the treatment of pulmonary P. aeruginosa isolates, clearing potential infection reservoirs within the upper airway

Is there a vortex-glass transition in high-temperature superconductors?

We show that DC voltage versus current measurements of a YBCO micro-bridge in a magnetic field can be collapsed onto scaling functions proposed by Fisher, Fisher, and Huse, as is widely reported in the literature. We find, however, that good data collapse is achieved for a wide range of critical exponents and temperatures. These results strongly suggest that agreement with scaling alone does not prove the existence of a phase transition. We propose a criterion to determine if the data collapse is valid, and thus if a phase transition occurs. To our knowledge, none of the data reported in the literature meet our criterion.Comment: 4 pages, 4 figure

Spiroindolines Identify the Vesicular Acetylcholine Transporter as a Novel Target for Insecticide Action

The efficacy of all major insecticide classes continues to be eroded by the development of resistance mediated, in part, by selection of alleles encoding insecticide insensitive target proteins. The discovery of new insecticide classes acting at novel protein binding sites is therefore important for the continued protection of the food supply from insect predators, and of human and animal health from insect borne disease. Here we describe a novel class of insecticides (Spiroindolines) encompassing molecules that combine excellent activity against major agricultural pest species with low mammalian toxicity. We confidently assign the vesicular acetylcholine transporter as the molecular target of Spiroindolines through the combination of molecular genetics in model organisms with a pharmacological approach in insect tissues. The vesicular acetylcholine transporter can now be added to the list of validated insecticide targets in the acetylcholine signalling pathway and we anticipate that this will lead to the discovery of novel molecules useful in sustaining agriculture. In addition to their potential as insecticides and nematocides, Spiroindolines represent the only other class of chemical ligands for the vesicular acetylcholine transporter since those based on the discovery of vesamicol over 40 years ago, and as such, have potential to provide more selective tools for PET imaging in the diagnosis of neurodegenerative disease. They also provide novel biochemical tools for studies of the function of this protein family

Perceived effort in football athletes: the role of achievement goal theory and self-determination theory

This study examined the motivational determinants of athletes perceived effort in football considering the four-stage motivational sequence at the contextual level proposed by Hierarchical Model of Intrinsic and Extrinsic Motivation: task-involving climate, basic psychological needs, self-determined motivation (SDM), and perceived effort. Additionally, SEM multi-group analysis across different age-groups (U15, U17, U19, and U21 years) and serial mediation of basic psychological needs (BPNs) and SDM on the task-involving motivational climate and the perceived effort were also analyzed. Two independent samples of male football athletes (N = 403, N = 403), aged 13-20 years were enrolled in this study. The results support the adequacy of the structural model in explaining the perceived effort of football atheltes in all samples under analysis, and was invariant across U17, U19, and U21. However, it was not invariant across U15 and U17, U19 and U21. Furthermore, results from the serial mediation showed significant indirect effects in all samples, supporting self-determination theoretical assumptions, reinforcing the importance of BPNs satisfaction and behavioral regulation in the relation in analysis. The results show that when coaches promote a task-involving climate, the BPNs satisfaction of athletes improves. This climate will facilitate the regulation of their behaviors toward more autonomous forms of motivation, with positive outcomes in the athletes perceived effort.info:eu-repo/semantics/publishedVersio

Physicians and nurses use and recommend dietary supplements: report of a survey

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Does Work Affect Personality? A Study in Horses

It has been repeatedly hypothesized that job characteristics are related to changes in personality in humans, but often personality models still omit effects of life experience. Demonstrating reciprocal relationships between personality and work remains a challenge though, as in humans, many other influential factors may interfere. This study investigates this relationship by comparing the emotional reactivity of horses that differed only by their type of work. Horses are remarkable animal models to investigate this question as they share with humans working activities and their potential difficulties, such as “interpersonal” conflicts or “suppressed emotions”. An earlier study showed that different types of work could be associated with different chronic behavioural disorders. Here, we hypothesised that type of work would affect horses' personality. Therefore over one hundred adult horses, differing only by their work characteristics were presented standardised behavioural tests. Subjects lived under the same conditions (same housing, same food), were of the same sex (geldings), and mostly one of two breeds, and had not been genetically selected for their current type of work. This is to our knowledge the first time that a direct relationship between type of work and personality traits has been investigated. Our results show that horses from different types of work differ not as much in their overall emotional levels as in the ways they express emotions (i.e. behavioural profile). Extremes were dressage horses, which presented the highest excitation components, and voltige horses, which were the quietest. The horses' type of work was decided by the stall managers, mostly on their jumping abilities, but unconscious choice based on individual behavioural characteristics cannot be totally excluded. Further research would require manipulating type of work. Our results nevertheless agree with reports on humans and suggest that more attention should be given to work characteristics when evaluating personalities

Dietary supplement use among health care professionals enrolled in an online curriculum on herbs and dietary supplements

BACKGROUND: Although many health care professionals (HCPs) in the United States have been educated about and recommend dietary supplements, little is known about their personal use of dietary supplements and factors associated with their use. METHODS: We surveyed HCPs at the point of their enrollment in an on-line course about dietary supplements between September, 2004 and May, 2005. We used multivariable logistic regression to analyze demographic and practice factors associated with use of dietary supplements. RESULTS: Of the 1249 health care professionals surveyed, 81 % reported having used a vitamin, mineral, or other non-herbal dietary supplements in the last week. Use varied by profession with highest rates among nurses (88%), physician assistants or nurse practitioners (84 %) and the lowest rates among pharmacists (66%) and trainees (72%). The most frequently used supplements were multivitamins (60%), calcium (40%), vitamin B (31%), vitamin C (30%), and fish oil (24%). Factors associated with higher supplement use were older age, female, high knowledge of dietary supplements, and discussing dietary supplements with patients. In our adjusted model, nurses were more likely than other professionals to use a multivitamin and students were more likely to use calcium. CONCLUSION: Among HCPs enrolled in an on-line course about dietary supplements, women, older clinicians, those with higher knowledge and those who talk with patients about dietary supplements had higher use of dietary supplements. Additional research is necessary to understand the impact of professionals' personal use of dietary supplements on communication with patients about them

Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine

<p>Abstract</p> <p>Background</p> <p>Relapse of major depressive disorder (MDD) is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia) predict risk of relapse during the continuation and maintenance treatment of MDD.</p> <p>Methods</p> <p>A total of 570 patients with MDD were treated with open-label, flexible dose fluoxetine (range 20 to 60 mg; mean dose = 45.8 mg/day; SD = 15.1) for 12 weeks. Under double blind conditions, 262 patients who achieved clinical response were randomly assigned to continue fluoxetine or to switch to placebo for 52 weeks or until relapse. Residual sleep disturbance during the baseline visit of the double-blind phase was assessed using items 4, 5, 6 (insomnia) and 22, 23, 24 (hypersomnia) of the Hamilton Depression Rating Scale (HDRS). Survival analysis was utilized to determine the effect of residual sleep disturbance on risk of relapse.</p> <p>Results</p> <p>The severities of early (<it>P </it>> 0.05), middle (<it>P </it>> 0.05), late (<it>P </it>> 0.05), or total (<it>P </it>> 0.05) residual insomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Similarly, the severities of early bedtime (<it>P </it>> 0.05), oversleeping (<it>P </it>> 0.05), napping (<it>P </it>> 0.05), or total (<it>P </it>> 0.05) residual hypersomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment.</p> <p>Conclusion</p> <p>The present study did not identify the severity of residual sleep disturbance among fluoxetine responders to predict risk of MDD relapse. The size of our sample may have precluded us from identifying more modest effects of residual sleep disturbance on the risk of relapse in MDD patients. Future studies are needed to further explore the relationship between residual sleep disturbance and relapse in MDD.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT00427128</p