2,098 research outputs found

    Comparison of manual and semi-automated delineation of regions of interest for radioligand PET imaging analysis

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    BACKGROUND As imaging centers produce higher resolution research scans, the number of man-hours required to process regional data has become a major concern. Comparison of automated vs. manual methodology has not been reported for functional imaging. We explored validation of using automation to delineate regions of interest on positron emission tomography (PET) scans. The purpose of this study was to ascertain improvements in image processing time and reproducibility of a semi-automated brain region extraction (SABRE) method over manual delineation of regions of interest (ROIs). METHODS We compared 2 sets of partial volume corrected serotonin 1a receptor binding potentials (BPs) resulting from manual vs. semi-automated methods. BPs were obtained from subjects meeting consensus criteria for frontotemporal degeneration and from age- and gender-matched healthy controls. Two trained raters provided each set of data to conduct comparisons of inter-rater mean image processing time, rank order of BPs for 9 PET scans, intra- and inter-rater intraclass correlation coefficients (ICC), repeatability coefficients (RC), percentages of the average parameter value (RM%), and effect sizes of either method. RESULTS SABRE saved approximately 3 hours of processing time per PET subject over manual delineation (p 0.8) for both methods. RC and RM% were lower for the manual method across all ROIs, indicating less intra-rater variance across PET subjects' BPs. CONCLUSION SABRE demonstrated significant time savings and no significant difference in reproducibility over manual methods, justifying the use of SABRE in serotonin 1a receptor radioligand PET imaging analysis. This implies that semi-automated ROI delineation is a valid methodology for future PET imaging analysis

    Poor cognition is associated with increased abundance of Alistipes and decreased abundance of Clostridium genera in the gut

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    Background: Brain and gut health are intricately connected via the gut-microbiota-brain axis. Studies have shown that gut dysbiosis is associated with neurodegenerative diseases, including Alzheimer’s disease. However, how cognitive changes affects the gut microbiome structure is currently understudied. We aimed to assess the association between the gut microbiome and global cognitive scores in the Framingham Heart Study (FHS). Method: Our sample included 1,014 participants (mean age 52, 55% female) of the third generation FHS cohort with available stool samples, cognitive assessments, and no history of dementia or stroke (Table 1).We quantified the gut microbiome composition using 16S rRNA sequencing and performed multivariable association and differential abundance analyses, adjusting for age, sex, education, BMI, and other confounders. The global cognitive score (GCS) was built using neuropsychological assessments of four cognitive domains: Executive function (trails-making B); Processing speed (visual reproduction immediate and delayed); Language (similarity test); and Memory (logical memory immediate and delayed). Participants were additionally stratified by GCS with lower and higher scores indicating poor and normal cognition, respectively. Result: Our results (Figure 1) showed that individuals with poor cognition have a decreased abundance of genera Clostridium (OR = 0.69, 95% CI [0.55, 0.86]) and Ruminococcus (0.93, [0.93, 0.94]). Meanwhile, the genus Alistipes, previously connected to anxiety, chronic fatigue syndrome, depression, and hypertension, was more abundant (1.06, [1.05, 1.06]) in the poor cognition group. Moreover, the genus Pseudobutyrivibrio, a butyrate-producing bacteria from the rumen, was also found to be highly abundant (1.12, [1.11, 1.14]) in the poor cognition compared to normal. Finally, there was no difference in alpha and beta diversity between cognitive groups (Figure 2). Conclusion: Our study suggests that the abundance of several genera, including Pseudobutyrivibrio, Alistipes, Ruminococcus, and Clostridium is associated with cognition in middle-age. Clostridium was previously proposed as novel probiotics for human health, and increasing its abundance was viewed as an effective strategy to regulate and maintain the homeostasis of the gut microbiota. As all these bacteria have neuroprotective effects, manipulating their abundance through diet and pre/pro-biotics could be a research path for preserving global cognitive function in the future

    Local Conditions, Not Regional Gradients, Drive Demographic Variation of Giant Ragweed (Ambrosia trifida) and Common Sunflower (Helianthus annuus) Across Northern U.S. Maize Belt

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    Knowledge of environmental factors influencing demography of weed species will improve understanding of current and future weed invasions. The objective of this study was to quantify regional-scale variation in vital rates of giant ragweed and common sunflower. To accomplish this objective, a common field experiment was conducted across seven sites between 2006 and 2008 throughout the north central U.S. maize belt. Demographic parameters of both weed species were measured in intra- and interspecific competitive environments, and environmental data were collected within site-years. Site was the strongest predictor of belowground vital rates (summer and winter seed survival and seedling recruitment), indicating sensitivity to local abiotic conditions. However, biotic factors influenced aboveground vital rates (seedling survival and fecundity). Partial least squares regression (PLSR) indicated that demography of both species was most strongly influenced by thermal time and precipitation. The first PLSR components, both characterized by thermal time, explained 63.2% and 77.0% of variation in the demography of giant ragweed and common sunflower, respectively; the second PLSR components, both characterized by precipitation, explained 18.3% and 8.5% of variation, respectively. The influence of temperature and precipitation is important in understanding the population dynamics and potential distribution of these species in response to climate change

    Specific genetic markers for detecting subtypes of dengue virus serotype-2 in isolates from the states of Oaxaca and Veracruz, Mexico

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    <p>Abstract</p> <p>Background</p> <p>Dengue (DEN) is an infectious disease caused by the DEN virus (DENV), which belongs to the <it>Flavivirus </it>genus in the family <it>Flaviviridae</it>. It has a (+) sense RNA genome and is mainly transmitted to humans by the vector mosquito <it>Aedes aegypti</it>. Dengue fever (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely related virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Epidemiological and evolutionary studies have indicated that host and viral factors are involved in determining disease outcome and have proved the importance of viral genotype in causing severe epidemics. Host immune status and mosquito vectorial capacity are also important influences on the severity of infection. Therefore, an understanding of the relationship between virus variants with altered amino acids and high pathogenicity will provide more information on the molecular epidemiology of DEN. Accordingly, knowledge of the DENV serotypes and genotypes circulating in the latest DEN outbreaks around the world, including Mexico, will contribute to understanding DEN infections.</p> <p>Results</p> <p>1. We obtained 88 isolates of DENV, 27 from Oaxaca and 61 from Veracruz. 2. Of these 88 isolates, 16 were serotype 1; 62 serotype 2; 7 serotype 3; and 2 serotype 4. One isolate had 2 serotypes (DENV-2 and -1). 3. Partial nucleotide sequences of the genes encoding C- prM (14 sequences), the NS3 helicase domain (7 sequences), the NS5 S-adenosyl methionine transferase domain (7 sequences) and the RNA-dependent RNA polymerase (RdRp) domain (18 sequences) were obtained. Phylogenetic analysis showed that DENV-2 isolates belonged to the Asian/American genotype. In addition, the Asian/American genotype was divided into two clusters, one containing the isolates from 2001 and the other the isolates from 2005–2006 with high bootstrap support of 94%.</p> <p>Conclusion</p> <p>DENV-2 was the predominant serotype in the DF and DHF outbreak from 2005 to 2006 in Oaxaca State as well as in the 2006 outbreak in Veracruz State, with the Asian/American genotype prevalent in both states. Interestingly, DENV-1 and DENV-2 were the only serotypes related to DHF cases. In contrast, DENV-3 and DENV-4 were poorly represented according to epidemiological data reported in Mexico. We found that isoleucine was replaced by valine at residue 106 of protein C in the isolates from these 2005–2006 outbreaks and in those from the 1997, 1998 and 2001 outbreaks in the Caribbean islands. We suggested that this amino acid change may be used as a signature for isolates arising in the Caribbean islands and pertaining to the Asian/American genotype. Other amino acid changes are specific for the Asian/American, Asian and American strains.</p

    Perivascular spaces in the brain:anatomy, physiology and pathology

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    Perivascular spaces include a variety of passageways around arterioles, capillaries and venules in the brain, along which a range of substances can move. Although perivascular spaces were first identified over 150 years ago, they have come to prominence recently owing to advances in knowledge of their roles in clearance of interstitial fluid and waste from the brain, particularly during sleep, and in the pathogenesis of small vessel disease, Alzheimer disease and other neurodegenerative and inflammatory disorders. Experimental advances have facilitated in vivo studies of perivascular space function in intact rodent models during wakefulness and sleep, and MRI in humans has enabled perivascular space morphology to be related to cognitive function, vascular risk factors, vascular and neurodegenerative brain lesions, sleep patterns and cerebral haemodynamics. Many questions about perivascular spaces remain, but what is now clear is that normal perivascular space function is important for maintaining brain health. Here, we review perivascular space anatomy, physiology and pathology, particularly as seen with MRI in humans, and consider translation from models to humans to highlight knowns, unknowns, controversies and clinical relevance

    Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri

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    Background The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely. Results Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system. Conclusions In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen.publishedVersio
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