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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.
Analysis of human remains and a copper band found in the center of a Late Archaic (ca. 5000–3000 cal BP) shell ring demonstrate an exchange network between the Great Lakes and the coastal southeast United States. Similarities in mortuary practices suggest that the movement of objects between these two regions was more direct and unmediated than archaeologists previously assumed based on “down-the-line” models of exchange. These findings challenge prevalent notions that view preagricultural Native American communities as relatively isolated from one another and suggest instead that wide social networks spanned much of North America thousands of years before the advent of domestication.
Individual plant stomata were studied within a sealed environmental chamber that encloses a volume of space around a microscope objective. A leaf that is attached to a plant is secured to a temperature-controlled microscope stage, and the top surface of the leaf is illuminated via the microscope's light source while stomata on the underside of the leaf are observed through a microscope objective. Stomatal responses are observed on a leaf exposed to environmental conditions including various illuminations and changes in ambient CO2 level, at a given temperature.
Stomata (singular, “stoma”) are tiny pores through which plants breathe. Stomata are found on the upper and lower sides of leaves, on flower petals, on stems, and on roots. Scientists survey plant surfaces to determine the density and size of stomata and relate these findings to properties of the environment, such as temperature and the amounts of sunlight, humidity, oxygen, and carbon dioxide in the air when a leaf is formed. Stomata of various plants are suitable subjects for classroom laboratory activities since they may be examined by light microscopy.
The U.S. Patent and Trademark Office (PTO) encourages
independent inventors who are not patent
professionals to file and prosecute their own patent
applications. Self-help books are useful guides for
navigating through the PTO’s many laws and rules.
When an inventor has an idea, he should document it,
have the document witnessed, search all public
records for novelty and unobviousness, and finally
file an application with the PTO. The inventor
defends his idea with an Examiner from the PTO and,
if all requirements are met, receives a patent that
grants the inventor a monopoly to make, use, and
sell his invention for a period of time.
Healthy adults (n 30) participated in a placebo-controlled, randomised, double-blinded, cross-over study consisting of two 28 d treatments (β2-1 fructan or maltodextrin; 3×5 g/d) separated by a 14-d washout. Subjects provided 1 d faecal collections at days 0 and 28 of each treatment. The ability of faecal bacteria to metabolise β2-1 fructan was common; eighty-seven species (thirty genera, and four phyla) were isolated using anaerobic medium containing β2-1 fructan as the sole carbohydrate source. β2-1 fructan altered the faecal community as determined through analysis of terminal restriction fragment length polymorphisms and 16S rRNA genes. Supplementation with β2-1 fructan reduced faecal community richness, and two patterns of community change were observed. In most subjects, β2-1 fructan reduced the content of phylotypes aligning within the Bacteroides, whereas increasing those aligning within bifidobacteria, Faecalibacterium and the family Lachnospiraceae. In the remaining subjects, supplementation increased the abundance of Bacteroidetes and to a lesser extent bifidobacteria, accompanied by decreases within the Faecalibacterium and family Lachnospiraceae. β2-1 Fructan had no impact on the metagenome or glycoside hydrolase profiles in faeces from four subjects. Few relationships were found between the faecal bacterial community and various host parameters; Bacteroidetes content correlated with faecal propionate, subjects whose faecal community contained higher Bacteroidetes produced more caproic acid independent of treatment, and subjects having lower faecal Bacteroidetes exhibited increased concentrations of serum lipopolysaccharide and lipopolysaccharide binding protein independent of treatment. We found no evidence to support a defined health benefit for the use of β2-1 fructans in healthy subjects.
β2-1 Fructans are purported to improve health by stimulating growth of colonic bifidobacteria, increasing host resistance to pathogens and stimulating the immune system. However, in healthy adults, the benefits of supplementation remain undefined. Adults (thirteen men, seventeen women) participated in a double-blinded, placebo-controlled, randomised, cross-over study consisting of two 28-d treatments separated by a 14-d washout period. Subjects’ regular diets were supplemented with β2-1 fructan or placebo (maltodextrin) at 3×5 g/d. Fasting blood and 1-d faecal collections were obtained at the beginning and at the end of each phase. Blood was analysed for clinical, biochemical and immunological variables. Determinations of well-being and general health, gastrointestinal (GI) symptoms, regularity, faecal SCFA content, residual faecal β2-1 fructans and faecal bifidobacteria content were undertaken. β2-1 Fructan supplementation had no effect on blood lipid or cholesterol concentrations or on circulating lymphocyte and macrophage numbers, but significantly increased serum lipopolysaccharide, faecal SCFA, faecal bifidobacteria and indigestion. With respect to immune function, β2-1 fructan supplementation increased serum IL-4, circulating percentages of CD282+/TLR2+ myeloid dendritic cells and ex vivo responsiveness to a toll-like receptor 2 agonist. β2-1 Fructans also decreased serum IL-10, but did not affect C-reactive protein or serum/faecal Ig concentrations. No differences in host well-being were associated with either treatment, although the self-reported incidence of GI symptoms and headaches increased during the β2-1 fructan phase. Although β2-1 fructan supplementation increased faecal bifidobacteria, this change was not directly related to any of the determined host parameters.
This paper reviews recent developments in the production and use of unconventional natural gas in the United States with a focus on water and greenhouse gas emission implications. If unconventional natural gas in the U.S. is produced responsibly, transported and distributed with little leakage, and incorporated into integrated energy systems that are designed for future resiliency, it could play a significant role in realizing a more sustainable energy future; however, the increased use of natural gas as a substitute for more carbon intensive fuels will alone not substantially alter world carbon dioxide concentration projections.
This paper reviews recent developments in the production and use of unconventional natural gas in the United States with a focus on environmental impacts. Specifically, we focus on water management and greenhouse gas emission implications. If unconventional natural gas in the United States is produced responsibly, transported and distributed with little leakage, and incorporated into integrated energy systems that are designed for future resiliency, it could play a significant role in realizing a more sustainable energy future. The cutting-edge of industry water management practices gives a picture of how this transition is unfolding, although much opportunity remains to minimize water use and related environmental impacts. The role of natural gas to mitigate climate forcing is less clear. While natural gas has low CO2 emissions upon direct use, methane leakage and long term climate effects lead to the conclusion that increased use of natural gas as a substitute for more carbon intensive fuels will not substantially alter world carbon dioxide concentration projections, and that other zero or low carbon energy sources will be needed to limit GHG concentrations. We conclude with some possible avenues for further work.
We have investigated surface modification methods for avalanche photodiodes using dielectrics deposited by atomic layer deposition (ALD). Arrays of mesa GaN APDs were fabricated, and ALD Al2O3 was used for sidewall passivation prior to completing the APD array. The use of ALD Al2O3 in this manner was observed to result in a large average improvement in APD dark current when compared with devices using more conventional SiO2 passivation layers produced by chemical vapor deposition. Co-processed metal-oxide-semiconductor (MOS) capacitors fabricated with the same passivation layers show significant improvement in electrical interface quality for devices with ALD Al2O3.
Well-designed digital games are exceptionally successful at helping learners to build accurate intuitive understandings of the concepts and processes at the heart of those games owing to the situated and enacted nature of good game play (e.g., Gee, 2003/2007). Most commercial games fall short as platforms for learning because they do not help people articulate and connect their evolving intuitive understandings to more explicit formalized structures that would support transfer of knowledge to other contexts. Games hold the potential, however, to support learners in integrating their tacit spontaneous concepts with instructed concepts, thus preparing learners for future learning through a flexible and powerful foundation of conceptual understanding and skills (Clark et al., 2009a). The integration of prediction and explanation mechanics into game play potentially provides tools for supporting this extension from tacit to explicit by helping players articulate and explore the connections between the science-based dynamics present in the game and the formalized scientific principles they instantiate. This chapter explores these possibilities and proposes an example of how this might be accomplished in a physics-based game.
Background: Digital Games for Science Learning
This perspective that games provide significant potential affordances for science learning is not idiosyncratic. In 2006, the Federation of American Scientists issued a widely publicized report stating their belief that games offer a powerful new tool to support education and encouraging governmental and private organizational support for expanded funded research into the application of complex gaming environments for learning. In 2009, a special issue of Science (Hines, Jasny, & Merris, 2009) echoed and expanded this call. Later in 2009, the National Research Councilconvened a committee and workshop to explore this potential of games and simulations for science learning in greater depth.