Pilot and Feasibility Test of an Implementation Intention Intervention to Improve Fruit and Vegetable Intake Among Women with Low Socioeconomic Status

Fruit and vegetable intake (FVI), a modifiable risk factor for chronic diseases, is lower in low socioeconomic status (SES) populations. Implementation intentions (a specific type of planning that extends the Theory of Planned Behavior) has been studied to improve FVI, but not exclusively with low SES groups. Using mixed methods, we evaluated the feasibility, acceptability, and preliminary efficacy of an implementation intention intervention (versus a general plan) to increase FVI in women with low SES. For the pilot randomized controlled trial, demographics, body mass index, attitude, perceived behavioral control, goal intention strength, and FVI were measured at baseline and FVI again 1-month following the intervention. Feasibility data were collected for recruitment, randomization, retention, and assessment procedures and compared to predetermined targets. Semi-structured interview data was analyzed for emergent themes regarding acceptability of the trial. Preliminary efficacy of the intervention to improve FVI was analyzed descriptively. Feasibility targets were met for randomization (100% vs. ≥80% target), retention (93.5% vs. ≥70% target) and the assessment metrics missing data points (2% vs. ≤10% target) and days from intervention to follow up (mean=69.2, sd=42.6 vs.days). Targets for recruitment were not met with the exception of participants giving informed consent (100% vs. ≥70% target). Participants described the intervention as enjoyable and reported behavioral constructs outside of those measured as important to improve FVI. Limited efficacy analysis suggested that both groups increased their FVI (experimental: +0.17 servings per day, 95% CI: -0.85, 1.20; control: +0.50 servings per day, 95% CI: -0.56, 1.58). Further research which examines interventions based upon behavior change models to improve dietary health behaviors in marginalized groups is needed

Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates

The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.Comment: 14 pages, 4 figure

Sparticle Spectrum of Large Volume Compactification

We examine the large volume compactification of Type IIB string theory or its F theory limit and the associated supersymmetry breakdown and soft terms. It is crucial to incorporate the loop-induced moduli mixing, originating from radiative corrections to the Kahler potential. We show that in the presence of moduli mixing, soft scalar masses generically receive a D-term contribution of the order of the gravitino mass m_{3/2} when the visible sector cycle is stabilized by the D-term potential of an anomalous U(1) gauge symmetry, while the moduli-mediated gaugino masses and A-parameters tend to be of the order of m_{3/2}/8pi^2. It is noticed also that a too large moduli mixing can destabilize the large volume solution by making it a saddle point.Comment: 29 page

Correlation in chicken between the marker LEI0258 alleles and Major Histocompatibility Complex sequences

<p>Abstract</p> <p>Background</p> <p>The LEI0258 marker is located within the B region of the chicken Major Histocompatibility Complex (MHC), and is surprisingly well associated with serology. Therefore, the correlation between the LEI0258 alleles and the MHC class I and the class II alleles at the level of sequences is worth investigating in chickens. Here we describe to which extent the LEI0258 alleles are associated with alleles of classical class I genes and non-classical class II genes, in reference animals as well as local breeds with unknown MHC haplotypes.</p> <p>Methods</p> <p>For the class I region, in an exploratory project, we studied 10 animals from 3 breeds: Rhode Island Red, White Leghorn and Fayoumi chickens, by cloning and sequencing <it>B-F1</it> and <it>B-F2</it> cDNA from exon 1 to 3’UTR. For the class II region, we reconstructed haplotypes of the 8.8 kb genomic region encompassing three non-classical class II genes: <it>B-DMA</it>, <it>B-DMB1</it> and <it>B-DMB2</it>, for 146 animals from more than 50 breeds including wild species of jungle fowls.</p> <p>Results</p> <p>Overall we found that the LEI0258 marker genotypes gave good indications of the MHC haplotypes, and a very good predictions (>0.95) of the heterozygosity of an animal at the MHC locus.</p> <p>Conclusions</p> <p>Our results show that the LEI0258 alleles are strongly associated with haplotypes of classical class I genes and non-classical class II genes, unravelling the reasons why this marker is becoming the reference marker for MHC genotyping in chickens.</p

A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation

Nanoparticles introduced in living cells are capable of strongly promoting the aggregation of peptides and proteins. We use here molecular dynamics simulations to characterise in detail the process by which nanoparticle surfaces catalyse the self- assembly of peptides into fibrillar structures. The simulation of a system of hundreds of peptides over the millisecond timescale enables us to show that the mechanism of aggregation involves a first phase in which small structurally disordered oligomers assemble onto the nanoparticle and a second phase in which they evolve into highly ordered beta-sheets as their size increases

Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

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MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

Development and preliminary evaluation of a quality of life measure targeted at dementia caregivers

<p>Abstract</p> <p>Background</p> <p>Providing care for individuals with a progressive, debilitating condition such as dementia can adversely impact the quality of life (QOL) of informal caregivers. To date, there is no existing caregiver quality of life measure for dementia caregivers with breadth of coverage or that is applicable to caregivers of diverse ethnic backgrounds. The purpose of this study was to develop and evaluate a caregiver-targeted quality-of-life measure (CGQOL) for informal caregivers of persons with dementia that can be used with caregivers from a variety of ethnicities.</p> <p>Methods</p> <p>91 items were field tested by telephone interviews with 179 English-speaking and 21 monolingual Spanish-speaking caregivers of persons with dementia. Repeat interviews were conducted with 71 caregivers. Administration time, scale score distributions, item-scale correlations, reliability, and associations of scales with patient and caregiver demographic and caregiving characteristics were estimated. Structure of associations among scales was examined using exploratory factor analysis.</p> <p>Results</p> <p>Item analysis yielded 80 items distributed across 10 scales, with median administration time of 17 minutes [IQR 13.5–22 minutes] and minimal missing data. There were few floor or ceiling effects in scale score distributions. Internal consistency reliability was ≥ 0.78 for all scales; test-retest reliability (intraclass correlation) estimates exceeded 0.70 for 6 scales. More hours weekly spent in caregiving was uniquely associated with worse quality of life on 8 scales (p's ≤ 0.05). Three higher-order dimensions of caregiving assistance, emotional and social concerns, and spirituality and benefits were identified.</p> <p>Conclusion</p> <p>These preliminary results support subsequent evaluation of test-retest reliability, construct validity, and responsiveness to change of this quality-of-life measure for caregivers from diverse ethnicities.</p