Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice

Peer reviewedPublisher PD

Assessing validity of a short food frequency questionnaire on present dietary intake of elderly Icelanders

<p>Abstract</p> <p>Background</p> <p>Few studies exist on the validity of food frequency questionnaires (FFQs) administered to elderly people. The aim of this study was to assess the validity of a short FFQ on present dietary intake, developed specially for the AGES-Reykjavik Study, which includes 5,764 elderly individuals. Assessing the validity of FFQs is essential before they are used in studies on diet-related disease risk and health outcomes.</p> <p>Method</p> <p>128 healthy elderly participants (74 y ± 5.7; 58.6% female) answered the AGES-FFQ, and subsequently filled out a 3-day weighed food record. Validity of the AGES-FFQ was assessed by comparing its answers to the dietary data obtained from the weighed food records, using Spearman's rank correlation, Chi-Square/Kendall's tau, and a Jonckheere-Terpstra test for trend.</p> <p>Result</p> <p>For men a correlation ≥ 0.4 was found for potatoes, fresh fruits, oatmeal/muesli, cakes/cookies, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee, tea and sugar in coffee/tea (r = 0.40-0.71). A lower, but acceptable, correlation was also found for raw vegetables (r = 0.33). The highest correlation for women was found for consumption of rye bread, oatmeal/muesli, raw vegetables, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee and tea (r = 0.40-0.61). An acceptable correlation was also found for fish topping/salad, fresh fruit, blood/liver sausage, whole-wheat bread, and sugar in coffee/tea (r = 0.28-0.37). Questions on meat/fish meals, cooked vegetables and soft drinks did not show a significant correlation to the reference method. Pearson Chi-Square and Kendall's tau showed similar results, as did the Jonckheere-Terpstra trend test.</p> <p>Conclusion</p> <p>A majority of the questions in the AGES-FFQ had an acceptable correlation and may be used to rank individuals according to their level of intake of several important foods/food groups. The AGES-FFQ on present diet may therefore be used to study the relationship between consumption of several specific foods/food groups and various health-related endpoints gathered in the AGES-Reykjavik Study.</p

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates

Protein homeostasis is critical for cellular survival and its dysregulation has been implicated in Alzheimer's disease (AD) and other neurodegenerative disorders. Despite the growing appreciation of the pathogenic mechanisms involved in familial forms of AD, much less is known about the sporadic cases. Aggregates found in both familial and sporadic AD often include proteins other than those typically associated with the disease. One such protein is a mutant form of ubiquitin, UBB+1, a frameshift product generated by molecular misreading of a wild-type ubiquitin gene. UBB+1 has been associated with multiple disorders. UBB+1 cannot function as a ubiquitin molecule, and it is itself a substrate for degradation by the ubiquitin/proteasome system (UPS). Accumulation of UBB+1 impairs the proteasome system and enhances toxic protein aggregation, ultimately resulting in cell death. Here, we describe a novel model system to investigate how UBB+1 impairs UPS function and whether it plays a causal role in protein aggregation. We expressed a protein analogous to UBB+1 in yeast (Ubext) and demonstrated that it caused UPS impairment. Blocking ubiquitination of Ubext or weakening its interactions with other ubiquitin-processing proteins reduced the UPS impairment. Expression of Ubext altered the conjugation of wild-type ubiquitin to a UPS substrate. The expression of Ubext markedly enhanced cellular susceptibility to toxic protein aggregates but, surprisingly, did not induce or alter nontoxic protein aggregates in yeast. Taken together, these results suggest that Ubext interacts with more than one protein to elicit impairment of the UPS and affect protein aggregate toxicity. Furthermore, we suggest a model whereby chronic UPS impairment could inflict deleterious consequences on proper protein aggregate sequestration

From biomedicine to natural history research: EST resources for ambystomatid salamanders

BACKGROUND: Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories. RESULTS: Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the A. t. tigrinum ESTs were obtained primarily from a normalized library, an approximately equal number of contigs were obtained for each species, with 21,091 unique contigs identified overall. The 10,592 contigs that showed significant similarity to sequences from the human RefSeq database reflected a diverse array of molecular functions and biological processes, with many corresponding to genes expressed during spinal cord injury in rat and fin regeneration in zebrafish. To demonstrate the utility of these EST resources, we searched databases to identify probes for regeneration research, characterized intra- and interspecific nucleotide polymorphism, saturated a human – Ambystoma synteny group with marker loci, and extended PCR primer sets designed for A. mexicanum / A. t. tigrinum orthologues to a related tiger salamander species. CONCLUSIONS: Our study highlights the value of developing resources in traditional model systems where the likelihood of information transfer to multiple, closely related taxa is high, thus simultaneously enabling both laboratory and natural history research

Time-Lapse Imaging of the Dynamics of CNS Glial-Axonal Interactions In Vitro and Ex Vivo

Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize the various stages of myelination.We took two approaches to follow myelination over time: i) time-lapse imaging of mixed CNS myelinating cultures generated from mouse spinal cord to which exogenous GFP-labelled murine cells were added, and ii) ex vivo imaging of the spinal cord of shiverer (Mbp mutant) mice, transplanted with GFP-labelled murine neurospheres. We demonstrate that oligodendrocyte-axonal interactions are dynamic events with continuous retraction and extension of oligodendroglial processes. Using cytoplasmic and membrane-GFP labelled cells to examine different components of the myelin-like sheath, we provide evidence from time-lapse fluorescence microscopy and confocal microscopy that the oligodendrocytes' cytoplasm-filled processes initially spiral around the axon in a corkscrew-like manner. This is followed subsequently by focal expansion of the corkscrew process to form short cuffs, which then extend longitudinally along the axons. We predict from this model that these spiral cuffs must extend over each other first before extending to form internodes of myelin.These experiments show the feasibility of visualizing the dynamics of glial-axonal interaction during myelination over time. Moreover, these approaches complement each other with the in vitro approach allowing visualization of an entire internodal length of myelin and the ex vivo approach validating the in vitro data

Genome­-wide association study of alcohol consumption and genetic overlap with other health-­related traits in UK Biobank (<i>N </i>=112,117)

Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 14 loci. These include single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (se=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 0.90 (s.e.=0.09, P-value=7.16 × 10(-23)). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG=0.18, s.e.=0.03), high-density lipoprotein cholesterol (rG=0.28, s.e.=0.05), smoking (rG=0.40, s.e.=0.06) and various anthropometric traits (for example, overweight, rG=-0.19, s.e.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption

Research on Teaching and Learning Probability

This book summarizes the vast amount of research related to teaching and learning probability that has been conducted for more than 50 years in a variety of disciplines. It begins with a synthesis of the most important probability interpretations throughout history: intuitive, classical, frequentist, subjective, logical propensity and axiomatic views. It discusses their possible applications, philosophical problems, as well as their potential and the level of interest they enjoy at different educational levels. Next, the book describes the main features of probabilistic thinking and reasoning, including the contrast to classical logic, probability language features, the role of intuitions, as well as paradoxes and the relevance of modeling. It presents an analysis of the differences between conditioning and causation, the variability expression in data as a sum of random and causal variations, as well as those of probabilistic versus statistical thinking. This is followed by an analysis of probability’s role and main presence in school curricula and an outline of the central expectations in recent curricular guidelines at the primary, secondary and high school level in several countries. This book classifies and discusses in detail the three different research periods on students’ and people’s intuitions and difficulties concerning probability: early research focused on cognitive development, a period of heuristics and biases programs, and the current period marked by a multitude of foci, approaches and theoretical frameworks

Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study

Background: Vaccination was a core component for mitigating the 2009 influenza pandemic (pH1N1). However, a vaccination program's efficacy largely depends on population compliance. We examined general population decision-making for pH1N1 vaccination using a modified Theory of Planned Behaviour (TBP). Methodology: We conducted a longitudinal study, collecting data before and after the introduction of pH1N1 vaccine in Hong Kong. Structural equation modeling (SEM) tested if a modified TPB had explanatory utility for vaccine uptake among adults. Principal Findings: Among 896 subjects who completed both the baseline and the follow-up surveys, 7% (67/896) reported being "likely/very likely/certain" to be vaccinated (intent) but two months later only 0.8% (7/896) reported having received pH1N1 vaccination. Perception of low risk from pH1N1 (60%) and concerns regarding adverse effects of the vaccine (37%) were primary justifications for avoiding pH1N1 vaccination. Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = -0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30). Social norm (β = 0.70), anticipated regret (β = 0.19) and vaccination intention (β = 0.31) were positively associated with, and accounted for 70% of variance in vaccination planning, which, in turn subsequently predicted self-reported vaccination uptake (β = 0.36) accounting for 36% of variance in reported vaccination behaviour. Conclusions/Significance: Perceived low risk from pH1N1 and perceived high risk from pH1N1 vaccine inhibited pH1N1 vaccine uptake. Both the TPB and the additional components contributed to intended vaccination uptake but social norms and anticipated regret predominantly associated with vaccination intention and planning. Vaccination planning is a more significant proximal determinant of uptake of pH1N1 vaccine than is intention. Intention alone is an unreliable predictor of future vaccine uptake. © 2011 Liao et al.published_or_final_versio

Group Singing as a Resource for the Development of a Healthy Public

A growing body of evidence points to a wide range of benefits arising from participation in group singing. Group singing requires participants to engage with each other in a simultaneous musical dialogue in a pluralistic and emergent context, creating a coherent cultural expression through the reflexive negotiation of (musical) meaning manifest in the collective power of the human voice. As such, group singing might be taken – both literally and figuratively – as a potent form of ‘healthy public’, creating an ‘ideal’ community which participants can subsequently mobilise as a positive resource for everyday life. The experiences of a group of singers (n=78) who had participated in an outdoor singing project were collected and analysed using a three-layer research design consisting of: distributed data generation and interpretation, considered against comparative data from other singing groups (n=88); a focus group workshop (n=11); an unstructured interview (n=2). The study confirmed an expected perception of the social bonding effect of group singing, highlighting affordances for interpersonal attunement and attachment alongside a powerful individual sense of feeling ‘uplifted’. This study presents a novel perspective on group singing, highlighting the importance of participant experience as a means of understanding music as a holistic and complex adaptive system. It validates findings about group singing from previous studies - in particular the stability of the social bonding effect as a less variant characteristic in the face of environmental and other situational influences, alongside its capacity for mental health recovery. It establishes a subjective sociocultural and musical understanding of group singing, by expanding on these findings to centralise the importance of individual experience, and the consciousness of that experience as descriptive self-awareness. The ways in which participants describe and discuss their experiences of group singing and its benefits points to a complex interdependence between a number of musical, neurobiological and psychosocial mechanisms which might be independently and objectively analysed. An emerging theory is that at least some of the potency of group singing is as a resource where people can rehearse and perform ‘healthy’ relationships, further emphasising its potential as a resource for healthy publics