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Understanding the metabolic processes associated with aging is key to developing effective management and treatment strategies for age-related diseases. We investigated the metabolic profiles associated with age in a Taiwanese and an American population. ¹H NMR spectral profiles were generated for urine specimens collected from the Taiwanese Social Environment and Biomarkers of Aging Study (SEBAS; n = 857; age 54-91 years) and the Mid-Life in the USA study (MIDUS II; n = 1148; age 35-86 years). Multivariate and univariate linear projection methods revealed some common age-related characteristics in urinary metabolite profiles in the American and Taiwanese populations, as well as some distinctive features. In both cases, two metabolites--4-cresyl sulfate (4CS) and phenylacetylglutamine (PAG)--were positively associated with age. In addition, creatine and β-hydroxy-β-methylbutyrate (HMB) were negatively correlated with age in both populations (p < 4 × 10⁻⁶). These age-associated gradients in creatine and HMB reflect decreasing muscle mass with age. The systematic increase in PAG and 4CS was confirmed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). Both are products of concerted microbial-mammalian host cometabolism and indicate an age-related association with the balance of host-microbiome metabolism.

Background: β-amyloid is regarded as a significant factor in Alzheimer's disease: but inefficient therapies based on this rationale suggests that additional signalling molecules or intermediary mechanisms must be involved in the actual initiation of the characteristic degeneration of neurons. One clue could be that acetylcholinesterase, also present in amyloid plaques, is aberrant in peripheral tissues such as blood and adrenal medulla that can be implicated in Alzheimer's disease. The aim of this study was to assess the bioactivity of a fragment of acetylcholinesterase responsible for its non-enzymatic functions, a thirty amino acid peptide ("T30") which has homologies with β-amyloid., Methods: Cell viability was measured by sulforhodamine B assay and also lactate dehydrogenase assay: meanwhile, changes in the status of living cells was monitored by measuring release of acetylcholinesterase in cell perfusates using the Ellman reagent., Findings: T30 peptide and β-amyloid each have toxic effects on PC12 cells, comparable to hydrogen peroxide(.) However only the two peptides selectively then evoke a subsequent, enhanced release in acetylcholinesterase that could only be derived from the extant cells. Moreover, unlike hydrogen peroxide, the T30 peptide selectively shifted a sub-threshold dose of β-amyloid to a toxic effect, which also resulted in a comparable enhanced release of acetylcholinesterase., Interpretation: This is the first study comparing directly the bioactivity of β-amyloid with a peptide derived from acetylcholinesterase: the similarity in action suggests that the sequence homology between the two compounds might have a functional and/or pathological relevance. The subsequent enhanced release of acetylcholinesterase from the extant cells could reflect a primary 'compensatory' response of cells prone to degeneration, paradoxically providing further availability of the toxic C-terminal peptide to modulate the potency of β-amyloid. Such a cycle of events may provide new insights into the mechanism of continuing selective cell loss in Alzheimer's disease and related degenerative disorders.

Combining data from multiple analytical platforms is essential for comprehensive study of the molecular phenotype (metabotype) of a given biological sample. The metabolite profiles generated are intrinsically dependent on the analytical platforms, each requiring optimization of instrumental parameters, separation conditions, and sample extraction to deliver maximal biological information. An in-depth evaluation of extraction protocols for characterizing the metabolome of the hepatobiliary fluke Fasciola hepatica , using ultra performance liquid chromatography and capillary electrophoresis coupled with mass spectroscopy is presented. The spectrometric methods were characterized by performance, and metrics of merit were established, including precision, mass accuracy, selectivity, sensitivity, and platform stability. Although a core group of molecules was common to all methods, each platform contributed a unique set, whereby 142 metabolites out of 14,724 features were identified. A mixture design revealed that the chloroform:methanol:water proportion of 15:59:26 was globally the best composition for metabolite extraction across UPLC-MS and CE-MS platforms accommodating different columns and ionization modes. Despite the general assumption of the necessity of platform-adapted protocols for achieving effective metabotype characterization, we show that an appropriately designed single extraction procedure is able to fit the requirements of all technologies. This may constitute a paradigm shift in developing efficient protocols for high-throughput metabolite profiling with more-general analytical applicability.

In nature, the complexity and structure of microbial communities varies widely, ranging from a few species to thousands of species, and from highly structured to highly unstructured communities. Here, we describe the identity and functional capacity of microbial populations within distinct layers of a pristine, marine-derived, meromictic (stratified) lake (Ace Lake) in Antarctica. Nine million open reading frames were analyzed, representing microbial samples taken from six depths of the lake size fractionated on sequential 3.0, 0.8 and 0.1 μm filters, and including metaproteome data from matching 0.1 μm filters. We determine how the interactions of members of this highly structured and moderately complex community define the biogeochemical fluxes throughout the entire lake. Our view is that the health of this delicate ecosystem is dictated by the effects of the polar light cycle on the dominant role of green sulfur bacteria in primary production and nutrient cycling, and the influence of viruses/phage and phage resistance on the cooperation between members of the microbial community right throughout the lake. To test our assertions, and develop a framework applicable to other microbially driven ecosystems, we developed a mathematical model that describes how cooperation within a microbial system is impacted by periodic fluctuations in environmental parameters on key populations of microorganisms. Our study reveals a mutualistic structure within the microbial community throughout the lake that has arisen as the result of mechanistic interactions between the physico-chemical parameters and the selection of individual members of the community. By exhaustively describing and modelling interactions in Ace Lake, we have developed an approach that may be applicable to learning how environmental perturbations affect the microbial dynamics in more complex aquatic systems.

Viruses are abundant ubiquitous members of microbial communities and in the marine environment affect population structure and nutrient cycling by infecting and lysing primary producers. Antarctic lakes are microbially dominated ecosystems supporting truncated food webs in which viruses exert a major influence on the microbial loop. Here we report the discovery of a virophage (relative of the recently described Sputnik virophage) that preys on phycodnaviruses that infect prasinophytes (phototrophic algae). By performing metaproteogenomic analysis on samples from Organic Lake, a hypersaline meromictic lake in Antarctica, complete virophage and near-complete phycodnavirus genomes were obtained. By introducing the virophage as an additional predator of a predator-prey dynamic model we determined that the virophage stimulates secondary production through the microbial loop by reducing overall mortality of the host and increasing the frequency of blooms during polar summer light periods. Virophages remained abundant in the lake 2 y later and were represented by populations with a high level of major capsid protein sequence variation (25-100% identity). Virophage signatures were also found in neighboring Ace Lake (in abundance) and in two tropical lakes (hypersaline and fresh), an estuary, and an ocean upwelling site. These findings indicate that virophages regulate host-virus interactions, influence overall carbon flux in Organic Lake, and play previously unrecognized roles in diverse aquatic ecosystems.

Background: Food-borne pharyngitis outbreaks causing substantial morbidity have been documented., Objectives: To investigate an outbreak of food-borne Streptococcus beta hemolyticus group A pharyngitis among employees of a hitech company., Methods: We received a report on an unusually high rate of morbidity among employees of a company in September 2003. The Tel Aviv District Health Office conducted an epidemiological investigation of the outbreak., Results: Among the 278 people who attended a company party, 83 became ill. The overall attack rate was 29.8%. Information was available on 174 of 193 employees and family members who attended the party and worked in the Tel Aviv district. Forty-six of them became ill (attack rate 26.4%). The secondary attack rate was 3.8%. Most cases developed symptoms 24-48 hours following the event. Seven cases had throat cultures positive for Streptococcus beta hemolyticus group A. Three items were significantly associated with becoming sick: spring chicken (odds ratio 2.26, 95% confidence interval 1.11-4.63, P = 0.02), vegetable salad (OR 2.88 95% CI 1.40-5.94, P = 0.003) and corn (OR 7.73, 95% CI 3.18-18.80, P < 0.001). Eating corn remained significantly associated with pharyngitis after controlling for other food items consumed., Conclusions: We describe the epidemiological investigation of a large food-borne outbreak of Streptococcus beta hemolyticus group A pharyngitis most probably transmitted by corn. No previous publication has implicated corn. Food handlers and the public should be aware that they can transmit diseases to others. Physicians should be aware that streptococcal pharyngitis could be a foodborne disease and that outbreaks in a non-confined setting may be easily missed.

It has been proposed, and questioned, whether motor impairments in attention-deficit-hyperactivity disorder, combined type (ADHD-C) alone, developmental coordination disorder (DCD) alone, and ADHD-C and comorbid DCD (ADHD-C/DCD) may arise from disruption to a common set of cognitive functions and their related neural substrate. This study examined movement durations for real and imagined movements in a visually guided pointing task in 58 prepubertal children aged 8 to 12 years old with ADHD-C alone (n=14), ADHD-C/DCD (n=14), DCD alone (n=15), and an age-, sex-, and Full-scale IQ-matched healthy comparison group (n=15). There were 10 males and 4 or 5 females in each group. The DCD alone group demonstrated an inability to generate imagined movements that was not present in the ADHD-C group, with or without comorbid DCD, or healthy comparison participants. These findings add to the emerging literature characterizing intended and actual motor impairments associated with DCD alone.

Drug induced cognitive change is generally investigated using small sample sizes. In terms of null hypothesis significance testing (NHST) this can render a meaningful change non-significant, as a result of insufficient power in the statistical model. NHST leads to 'all or none' thinking, where a non-significant result is interpreted as an absence of change. An effect size calculation indicates the magnitude of change which has occurred post-intervention, and therefore whether a significant result is meaningful. We used a scopolamine challenge to demonstrate the usefulness of effect sizes. The aim of the study was to determine how effect sizes could describe the cognitive changes that occur following administration of subcutaneous scopolamine (s.c. scopolamine). Twenty four healthy young males (M = 32.6, sd = 4.5 years) were administered placebo and 0.2 mg, 0.4 mg & 0.6 mg of s.c. scopolamine using a 4-way crossover design. Memory, learning, psychomotor function, attention and executive function were assessed. Scopolamine significantly impaired performance on all tasks in a dose and time related manner. These results demonstrate the functionality of change scores to draw comparisons between different times and doses. This methodology overcomes the limitations of comparisons between studies using different tasks, doses and time at which cognitive functions are measured., ((c) 2008 John Wiley & Sons, Ltd.)

Background: The lycophyte Selaginella moellendorffii is a vascular plant that diverged from the fern/seed plant lineage at least 400 million years ago. Although genomic information for S. moellendorffii is starting to be produced, little is known about basic aspects of its molecular biology. In order to provide the first glimpse to the epigenetic landscape of this early divergent vascular plant, we used the methylation filtration technique. Methylation filtration genomic libraries select unmethylated DNA clones due to the presence of the methylation-dependent restriction endonuclease McrBC in the bacterial host., Results: We conducted a characterization of the DNA methylation patterns of the S. moellendorffii genome by sequencing a set of S. moellendorffii shotgun genomic clones, along with a set of methylation filtered clones. Chloroplast DNA, which is typically unmethylated, was enriched in the filtered library relative to the shotgun library, showing that there is DNA methylation in the extremely small S. moellendorffii genome. The filtered library also showed enrichment in expressed and gene-like sequences, while the highest-copy repeats were largely under-represented in this library. These results show that genes and repeats are differentially methylated in the S. moellendorffii genome, as occurs in other plants studied., Conclusion: Our results shed light on the genome methylation pattern in a member of a relatively unexplored plant lineage. The DNA methylation data reported here will help understanding the involvement of this epigenetic mark in fundamental biological processes, as well as the evolutionary aspects of epigenetics in land plants.

Background  Wandering behaviour is frequently seen in older people with cognitive impairment. The prevalence of patients exhibiting wandering behaviour has been estimated to be 11.6% on traditional units and 52.7% on Alzheimer's units. Wandering is one of the core behavioural characteristics that impact on familial carers and is likely to influence the decision to place a family member in an aged care environment. Considering the possible risks associated with wandering behaviour, the successful identification and management of wandering is essential. Wandering is also a problem for caregivers in the institutionalised setting, in terms of containment, usually being addressed by securing the environment. There has been some research conducted to assist in the understanding and management of wandering behaviour; however, the findings have been diverse resulting in a level of confusion about the best approaches to take. Objectives  This review aims to present the best available evidence on the management of wandering in older adults who reside in an aged care facility (both high and low care). Search strategy  An extensive search of keywords contained in the title and abstract, and relevant MeSH headings and descriptor terms was performed on the following databases: MEDLINE, CINAHL, PsychINFO, AGELINE, Cochrane Library, Embase, APAIS Health, Current Contents, Dare, Dissertation Abstracts, Personal Communication, Social Science Index. Selection criteria  Papers were selected if they focused on the treatment of wandering in an institutional setting. Some studies were not specifically examining wanderers over the age of 65 years as per the protocol requirements, but were included as it was felt that their findings could be applied to this age group. Data collection and analysis  Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data where possible. All other data were presented in a narrative summary. Results  Searches identified one care protocol, two systematic reviews and 24 other studies that satisfied the inclusion criteria. The following recommendations are divided into four categories of interventions (environmental, technology and safety, physical/psychosocial, and caregiving support and education) with only Level 1, 2 or 3 evidence presented. Environmental modifications  Gridlines placed in front of doors or covering exit door doorknobs or panic bars may be effective at reducing exit-seeking behaviour (Level 3b). Technology and safety  Mobile locator devices may be effective at enabling quick location of wandering residents (Level 3c). Physical/psychosocial interventions  Implementation of a walking group or an exercise program may reduce the incidence of disruptive wandering behaviour (Level 3b). Use of air mat therapy may reduce wandering behaviour for at least 15 min post therapy (Level 2). Providing music sessions (and reading sessions) may keep residents from wandering during the period of the session (Level 3b). Caregiving support and education  There is no evidence to support any interventions. Conclusions  The majority of the available research for which the guidelines are based upon was derived from observational studies or expert opinion (Level of evidence 3 or 4). More rigorous research is required to demonstrate the efficacy of these recommendations.

Objective: To assess the effect of gestational perchlorate exposure through drinking water on neonatal thyroxine (T(4))., Design: T(4) values were compared among newborns in Ramat Hasharon, Israel, whose mothers resided in suburbs where drinking water contained perchlorate < or = 340 microg/L (very high exposure, n = 97), 42-94 microg/L (high exposure, n = 216), and < 3 microg/L (low exposure, n = 843). In the very high and high exposure areas, T(4) values in newborns whose mothers drank tap water exclusively (as determined by a telephone interview) were analyzed as a subset. Serum perchlorate levels in blood from donors residing in the area were used as proxy indicators of exposure., Main Outcome: Neonatal T(4) values (mean +/- SD) in the very high, high, and low exposure groups were 13.9 +/- 3.8, 13.9 +/- 3.4, and 14.0 +/- 3.5 microg/dL, respectively (p = NS). Serum perchlorate concentrations in blood from donors residing in areas corresponding to these groups were 5.99 +/- 3.89, 1.19 +/- 1.37, and 0.44 +/- 0.55 microg/L, respectively. T(4) levels of neonates with putative gestational exposure to perchlorate in drinking water were not statistically different from controls., Conclusion: This study finds no change in neonatal T(4) levels despite maternal consumption of drinking water that contains perchlorate at levels in excess of the Environmental Protection Agency (EPA) drinking water equivalent level (24.5 microg/L) based on the National Research Council reference dose (RfD) [0.7 microg/(kg.day)]. Therefore the perchlorate RfD is likely to be protective of thyroid function in neonates of mothers with adequate iodide intake.

Neurosteroids play a significant role in neurodevelopment and are involved in a wide variety of psychopathological processes. There is accumulating evidence on their role in adult psychopathology, including Alzheimer disease, schizophrenia, mood disorder, anxiety disorders and post-traumatic stress disorder. Little is known, however, about the possible role of neurosteroids in child and adolescent psychopathology although there is increasing evidence for their critical role from the early stages of brain development until adolescence. In this review we focus on the involvement of neurosteroids in neurodevelopment and mental disorders in children and adolescents. Adequate physiological levels protect the developing neural system from insult and contribute to the regulation of brain organization and function. Neurosteroids may be involved in the pathophysiology and pharmacotherapy of a variety of disorders in children and adolescents, including schizophrenia, depression, eating disorders, aggressive behavior and attention deficit. The complex interaction between neurosteroids, neurodevelopment, life-events, genetics and mental disorders in children and adolescents merits further investigation.

Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.

The completion of the 5,373,180-bp genome sequence of the marine psychrophilic bacterium Colwellia psychrerythraea 34H, a model for the study of life in permanently cold environments, reveals capabilities important to carbon and nutrient cycling, bioremediation, production of secondary metabolites, and cold-adapted enzymes. From a genomic perspective, cold adaptation is suggested in several broad categories involving changes to the cell membrane fluidity, uptake and synthesis of compounds conferring cryotolerance, and strategies to overcome temperature-dependent barriers to carbon uptake. Modeling of three-dimensional protein homology from bacteria representing a range of optimal growth temperatures suggests changes to proteome composition that may enhance enzyme effectiveness at low temperatures. Comparative genome analyses suggest that the psychrophilic lifestyle is most likely conferred not by a unique set of genes but by a collection of synergistic changes in overall genome content and amino acid composition.

Football fans' views on their role in the home advantage were obtained by placing links to an internet questionnaire on supporters' websites. Altogether, 461 fans from clubs which had been promoted, relegated or unchanged in the past season of the English football leagues rated crowd support as significantly more influential than familiarity, travel, territoriality and referee bias in contributing to the home advantage. Fans felt responsible for inspiring their team to victory, took credit for distracting opponents, and believed that they could influence officials into making decisions in their team's favour. However, they did not accept personal blame for poor results. No effects for gender, age or the team's outcome in the promotion/relegation battle emerged, though season ticket holders were more extreme in their feelings of responsibility overall. Furthermore, it was suggested that mechanisms such as the perception of being superior to rivals can encourage fans to retain their allegiance to their teams, even when outcomes are disappointing. Indeed, affiliation may become so incorporated into self-identity that supporters may not have the option of abandoning their team, but instead perceive a reciprocal relationship in which both they and the team are expected to do their best to achieve success.

The occurrence of post-operative cognitive dysfunction is a distressing complication following surgery. In an effort to gain a more complete understanding of patients' cognitive recovery following surgical procedures common neuropsychological assessment tools have been adopted in a repeated measures design. It is widely regarded that this represents the most comprehensive method of determining cognitive status in this population but it has resulted in a number of statistical and conceptual difficulties in attempting to infer significant change. The current paper outlines these core difficulties and provides some potential methods to overcome these.

The Sagittarius dwarf tidal stream may be showering dark matter onto the solar neighborhood, which can change the results and interpretation of direct detection searches for weakly interacting massive particles (WIMPs). Stars in the stream may already have been detected in the solar neighborhood, and the dark matter in the stream is (0.3-25)% of the local density. Experiments should see an annually modulated steplike feature in the energy recoil spectrum that would be a smoking gun for WIMP detection. The total count rate in detectors is not a cosine curve in time and peaks at a different time of year than the standard case.

The translation of research findings into practice guidelines is an important aspect in maintaining the currency of practice and adding value to research. While there has been a large amount of published literature regarding the treatment and prevention of pressure ulcers, very few studies have attempted to provide clear clinical guidelines. The present study proposes a model to transform research into clinical guidelines whilst developing a series of guidelines that can be applied to a variety of clinical settings.

We illustrate the use of a PCR-based method by which the genomic DNA of a microorganism can be rapidly queried for the presence of type I modular polyketide synthase genes to clone and characterize, by sequence analysis and gene disruption, a major portion of the geldanamycin production gene cluster from Streptomyces hygroscopicus var. geldanus NRRL 3602.