Five views of a secret: does cognition change during middle adulthood?

This study examined five aspects of change (or stability) in cognitive abilities in middle adulthood across a 12-year period. Data come from the Interdisciplinary Study on Adult Development. The sample consisted of N = 346 adults (43.8 years on average, 48.6% female). In total, 11 cognitive tests were administered to assess fluid and crystallized intelligence, memory, and processing speed. In a first series of analyses, strong measurement invariance was established. Subsequently, structural stability, differential stability, stability of divergence, absolute stability, and the generality of changes were examined. Factor covariances were shown to be equal across time, implying structural stability. Stability coefficients were around .90 for fluid and crystallized intelligence, and speed, indicating high, yet not perfect differential stability. The coefficient for memory was .58. Only in processing speed the variance increased across time, indicating heterogeneity in interindividual development. Significant mean-level changes emerged, with an increase in crystallized intelligence and decline in the other three abilities. A number of correlations among changes in cognitive abilities were significant, implying that cognitive change

Changes in Cognition and Mortality in Relation to Exercise in Late Life: A Population Based Study

BACKGROUND: On average, cognition declines with age but this average hides considerable variability, including the chance of improvement. Here, we investigate how exercise is associated with cognitive change and mortality in older people and, particularly, whether exercise might paradoxically increase the risk of dementia by allowing people to live longer. METHODS AND PRINCIPAL FINDINGS: In the Canadian Study of Health and Aging (CSHA), of 8403 people who had baseline cognition measured and exercise reported at CSHA-1, 2219 had died and 5376 were re-examined at CSHA-2. We used a parametric Markov chain model to estimate the probabilities of cognitive improvement, decline, and death, adjusted for age and education, from any cognitive state as measured by the Modified Mini-Mental State Examination. High exercisers (at least three times per week, at least as intense as walking, n = 3264) had more frequent stable or improved cognition (42.3%, 95% confidence interval: 40.6-44.0) over 5 years than did low/no exercisers (all other exercisers and non exercisers, n = 4331) (27.8% (95% CI 26.4-29.2)). The difference widened as baseline cognition worsened. The proportion whose cognition declined was higher amongst the high exercisers but was more similar between exercise groups (39.4% (95% CI 37.7-41.1) for high exercisers versus 34.8% (95% CI 33.4-36.2) otherwise). People who did not exercise were also more likely to die (37.5% (95% CI 36.0-39.0) versus 18.3% (95% CI 16.9-19.7)). Even so, exercise conferred its greatest mortality benefit to people with the highest baseline cognition. CONCLUSIONS: Exercise is strongly associated with improving cognition. As the majority of mortality benefit of exercise is at the highest level of cognition, and declines as cognition declines, the net effect of exercise should be to improve cognition at the population level, even with more people living longer

Incorporating rich background knowledge for gene named entity classification and recognition

<p>Abstract</p> <p>Background</p> <p>Gene named entity classification and recognition are crucial preliminary steps of text mining in biomedical literature. Machine learning based methods have been used in this area with great success. In most state-of-the-art systems, elaborately designed lexical features, such as words, n-grams, and morphology patterns, have played a central part. However, this type of feature tends to cause extreme sparseness in feature space. As a result, out-of-vocabulary (OOV) terms in the training data are not modeled well due to lack of information.</p> <p>Results</p> <p>We propose a general framework for gene named entity representation, called feature coupling generalization (FCG). The basic idea is to generate higher level features using term frequency and co-occurrence information of highly indicative features in huge amount of unlabeled data. We examine its performance in a named entity classification task, which is designed to remove non-gene entries in a large dictionary derived from online resources. The results show that new features generated by FCG outperform lexical features by 5.97 F-score and 10.85 for OOV terms. Also in this framework each extension yields significant improvements and the sparse lexical features can be transformed into both a lower dimensional and more informative representation. A forward maximum match method based on the refined dictionary produces an F-score of 86.2 on BioCreative 2 GM test set. Then we combined the dictionary with a conditional random field (CRF) based gene mention tagger, achieving an F-score of 89.05, which improves the performance of the CRF-based tagger by 4.46 with little impact on the efficiency of the recognition system. A demo of the NER system is available at <url>http://202.118.75.18:8080/bioner</url>.</p

Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome

<p>Abstract</p> <p>Background</p> <p>Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI). However, the profile of these complications in patients with AKI caused by crush syndrome (CS) remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake.</p> <p>Methods</p> <p>One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divided into five groups: Group A was composed of victims without CS and AKI (904 cases); Group B was composed of patients with CS and AKI who haven't received renal replacement therapy (RRT) (57 cases); and Group C was composed of patients with CS and AKI receiving RRT (25 cases); Group D was composed of earthquake victims with AKI but without CS (26 cases); and Group E was composed of 18 healthy adult controls. The C-reactive protein (CRP), prealbumin, transferrin, interleukin-6 and TNF-α were measured and compared between Group E and 18 patients from Group C.</p> <p>Results</p> <p>The results indicate that participants in Group C had the highest level of serum creatinine, blood urea nitrogen and uric acid. Approximately 92% of patients with CS who had RRT were suffering from hypoalbuminemia. The interleukin-6 and CRP levels were significantly higher in patients with CS AKI receiving RRT than in the control group. Patients in Group C received the highest dosages of albumin, plasma or red blood cell transfusions. One patient in Group C died during treatment.</p> <p>Conclusions</p> <p>Malnutrition and inflammation was common in patients with earthquake-related CS and had a negative impact on the prognosis of these subjects. The results of this study indicate that the use of RRT, intensive nutritional supplementation and transfusion alleviated the degree of malnutrition and inflammation in hemodialysis patients with crush syndrome.</p

The Lothian Birth Cohort 1936: a study to examine influences on cognitive ageing from age 11 to age 70 and beyond

BACKGROUND: Cognitive ageing is a major burden for society and a major influence in lowering people's independence and quality of life. It is the most feared aspect of ageing. There are large individual differences in age-related cognitive changes. Seeking the determinants of cognitive ageing is a research priority. A limitation of many studies is the lack of a sufficiently long period between cognitive assessments to examine determinants. Here, the aim is to examine influences on cognitive ageing between childhood and old age. METHODS/DESIGN: The study is designed as a follow-up cohort study. The participants comprise surviving members of the Scottish Mental Survey of 1947 (SMS1947; N = 70,805) who reside in the Edinburgh area (Lothian) of Scotland. The SMS1947 applied a valid test of general intelligence to all children born in 1936 and attending Scottish schools in June 1947. A total of 1091 participants make up the Lothian Birth Cohort 1936. They undertook: a medical interview and examination; physical fitness testing; extensive cognitive testing (reasoning, memory, speed of information processing, and executive function); personality, quality of life and other psycho-social questionnaires; and a food frequency questionnaire. They have taken the same mental ability test (the Moray House Test No. 12) at age 11 and age 70. They provided blood samples for DNA extraction and testing and other biomarker analyses. Here we describe the background and aims of the study, the recruitment procedures and details of numbers tested, and the details of all examinations. DISCUSSION: The principal strength of this cohort is the rarely captured phenotype of lifetime cognitive change. There is additional rich information to examine the determinants of individual differences in this lifetime cognitive change. This protocol report is important in alerting other researchers to the data available in the cohort

Genome Dynamics of Short Oligonucleotides: The Example of Bacterial DNA Uptake Enhancing Sequences

Among the many bacteria naturally competent for transformation by DNA uptake—a phenomenon with significant clinical and financial implications— Pasteurellaceae and Neisseriaceae species preferentially take up DNA containing specific short sequences. The genomic overrepresentation of these DNA uptake enhancing sequences (DUES) causes preferential uptake of conspecific DNA, but the function(s) behind this overrepresentation and its evolution are still a matter for discovery. Here I analyze DUES genome dynamics and evolution and test the validity of the results to other selectively constrained oligonucleotides. I use statistical methods and computer simulations to examine DUESs accumulation in Haemophilus influenzae and Neisseria gonorrhoeae genomes. I analyze DUESs sequence and nucleotide frequencies, as well as those of all their mismatched forms, and prove the dependence of DUESs genomic overrepresentation on their preferential uptake by quantifying and correlating both characteristics. I then argue that mutation, uptake bias, and weak selection against DUESs in less constrained parts of the genome combined are sufficient enough to cause DUESs accumulation in susceptible parts of the genome with no need for other DUES function. The distribution of overrepresentation values across sequences with different mismatch loads compared to the DUES suggests a gradual yet not linear molecular drive of DNA sequences depending on their similarity to the DUES. Other genomically overrepresented sequences, both pro- and eukaryotic, show similar distribution of frequencies suggesting that the molecular drive reported above applies to other frequent oligonucleotides. Rare oligonucleotides, however, seem to be gradually drawn to genomic underrepresentation, thus, suggesting a molecular drag. To my knowledge this work provides the first clear evidence of the gradual evolution of selectively constrained oligonucleotides, including repeated, palindromic and protein/transcription factor-binding DNAs

Longevity in mice: is stress resistance a common factor?

A positive relationship between stress resistance and longevity has been reported in a multitude of studies in organisms ranging from yeast to mice. Several mouse lines have been discovered or developed that exhibit extended longevities when compared with normal, wild-type mice of the same genetic background. These long-living lines include the Ames dwarf, Snell dwarf, growth hormone receptor knockout (Laron dwarf), IGF-1 receptor heterozygote, Little, α-MUPA knockout, p66shc knockout, FIRKO, mClk-1 heterozygote, thioredoxin transgenic, and most recently the Klotho transgenic mouse. These mice are described in terms of the reported extended lifespans and studies involving resistance to stress. In addition, caloric restriction (CR) and stress resistance are briefly addressed for comparison with genetically altered mice. Although many of the long-living mice have GH/IGF-1/insulin signaling-related alterations and enhanced stress resistance, there are some that exhibit life extension without an obvious link to this hormone pathway. Resistance to oxidative stress is by far the most common system studied in long-living mice, but there is evidence of enhancement of resistance in other systems as well. The differences in stress resistance between long-living mutant and normal mice result from complex interrelationships among pathways that appear to coordinate signals of growth and metabolism, and subsequently result in differences in lifespan

Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata

The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S) mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations accompanying the evolution of fungal drug resistance in a human host, implicate the premier compensatory mutation mitigating the cost of echinocandin resistance, and suggest a new mechanism of echinocandin resistance with broad therapeutic potential

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591