The effect of the CYP1A2 -163 C\u3eA polymorphism on the metabolism of caffeine and effect on performance

Prior studies from our laboratory suggest that the -163 C \u3e A polymorphism of the Cytochrome P450 (CYP1A2) gene influences the ergogenic effect of caffeine. Although this polymorphism has been known to influence the inducibility of hepatic CYP1A2 and the rate of caffeine metabolism, levels of caffeine and/or metabolites have never been reported in these aforementioned studies (1, 12, 16). Thus, a mechanistic link between the polymorphism and the ergogenic effect of caffeine is lacking. The purpose of this study was to determine if the CYP1A2 polymorphism affected caffeine metabolism between the genotypes (AA homozygotes and C allele carriers). Twenty male subjects were recruited for this study. Subjects participated in two 3km cycling time trials with placebo (all-purpose flour) and caffeine (6mg/kg body weight anhydrous caffeine) supplementation. “Slow metabolizers” were characterized as possessing a “C” allele on the first intron of that gene (grouped AC heterozygotes, and CC homozygotes), and “fast metabolizers” were those who were homozygous for the A allele. C allele carriers had significantly higher serum caffeine after one hour (C allele carriers = 14.2 ± 1.8 ppm, AA homozygotes = 11.7 ± 1.7 ppm). While there was a main effect for caffeine ingestion on time trial performance, there was no caffeine x genotype interaction (C allele carriers: Placebo = 297 ± 20.8 sec, Caffeine = 292 ± 20 sec; AA homozygotes: Placebo = 318.3 ± 34.5 sec; Caffeine = 307.9 ± 21.9 sec). Results from this study suggest that C allele carriers have higher serum caffeine after one hour than AA homozygotes, consistent with the assertion that C allele carriers metabolize caffeine slower. These findings do not support a genetic influence on the ergogenic effect of caffeine in a 3km cycling trial

Mild Dehydration Led to Increased Difficulty Falling Asleep

Sleep is fundamental process that benefits health and overall quality of life which can be affected by various aspects of daily living such as dehydration. A study has yet to investigate the impacts of euhydration and mild dehydration on sleep. PURPOSE: The purpose of this study was to examine effects of euhydration, mild-dehydration, and ad libitum drinking on sleep. METHODS: Eighteen male participants (mean±SD; age, 23±4y; height, 175.8±5.7cm; weight, 80.1±9.7kg) reported to the laboratory with different hydration status for 4 consecutive mornings(Day 1, baseline; Day 2, euhydrated; Day 3, mild-dehydrated; Day 4, ad libitum drinking). Hydration status was monitored by first morning urine specific gravity (USG) and plasma osmolality. Sleepwas measured using the Karolinska sleep diary (KSD). RESULTS: USG (baseline, 1.024±0.006; euhydrated, 1.018±0.007; mild-dehydrated, 1.030±0.003; ad libitum, 1.021±0.008, pCONCLUSION: When subjects were mildly dehydrated, sleep duration was longer while it was more difficult to fall asleep. More research is necessary, but the results of this study suggest it may be important to maintain euhydration to fall asleep easier

Disruption of information processing in schizophrenia: The time perspective

AbstractWe review studies suggesting time disorders on both automatic and subjective levels in patients with schizophrenia. Patients have difficulty explicitly discriminating between simultaneous and asynchronous events, and ordering events in time. We discuss the relationship between these difficulties and impairments on a more elementary level. We showed that for undetectable stimulus onset asynchronies below 20ms, neither patients nor controls merge events in time, as previously believed. On the contrary, subjects implicitly distinguish between events even when evaluating them to be simultaneous. Furthermore, controls privilege the last stimulus, whereas patients seem to stay stuck on the first stimulus when asynchronies are sub-threshold. Combining previous results shows this to be true for patients even for asynchronies as short as 8ms. Moreover, this peculiarity predicts difficulties with detecting asynchronies longer than 50ms, suggesting an impact on the conscious ability to time events. Difficulties on the subjective level are also correlated with clinical disorganization. The results are interpreted within the framework of predictive coding which can account for an implicit ability to update events. These results complement a range of other results, by suggesting a difficulty with binding information in time as well as space, and by showing that information processing lacks continuity and stability in patients. The time perspective may help bridge the gap between cognitive impairments and clinical symptoms, by showing how the innermost structure of thought and experience is disrupted

CRISPR-UnLOCK: Multipurpose Cas9-Based Strategies for Conversion of Yeast Libraries and Strains

Citation: Roggenkamp E, Giersch RM, Wedeman E, Eaton M, Turnquist E, Schrock MN, Alkotami L, Jirakittisonthon T, Schluter-Pascua SE, Bayne GH, Wasko C, Halloran M and Finnigan GC (2017) CRISPR-UnLOCK: Multipurpose Cas9-Based Strategies for Conversion of Yeast Libraries and Strains. Front. Microbiol. 8:1773. doi: 10.3389/fmicb.2017.01773Saccharomyces cerevisiae continues to serve as a powerful model system for both basic biological research and industrial application. The development of genome-wide collections of individually manipulated strains (libraries) has allowed for high-throughput genetic screens and an emerging global view of this single-celled Eukaryote. The success of strain construction has relied on the innate ability of budding yeast to accept foreign DNA and perform homologous recombination, allowing for efficient plasmid construction (in vivo) and integration of desired sequences into the genome. The development of molecular toolkits and “integration cassettes” have provided fungal systems with a collection of strategies for tagging, deleting, or over-expressing target genes; typically, these consist of a C-terminal tag (epitope or fluorescent protein), a universal terminator sequence, and a selectable marker cassette to allow for convenient screening. However, there are logistical and technical obstacles to using these traditional genetic modules for complex strain construction (manipulation of many genomic targets in a single cell) or for the generation of entire genome-wide libraries. The recent introduction of the CRISPR/Cas gene editing technology has provided a powerful methodology for multiplexed editing in many biological systems including yeast. We have developed four distinct uses of the CRISPR biotechnology to generate yeast strains that utilizes the conversion of existing, commonly-used yeast libraries or strains. We present Cas9-based, marker-less methodologies for (i) N-terminal tagging, (ii) C-terminally tagging yeast genes with 18 unique fusions, (iii) conversion of fluorescently-tagged strains into newly engineered (or codon optimized) variants, and finally, (iv) use of a Cas9 “gene drive” system to rapidly achieve a homozygous state for a hypomorphic query allele in a diploid strain. These CRISPR-based methods demonstrate use of targeting universal sequences previously introduced into a genome

Die Weltwirtschaft im Wandel: Symposium 1975

Seit einigen Jahren verstärkt sich der Eindruck, daß die Weltwirtschaft in einem raschen Wandel begriffen ist. Die Entwicklungsländer fordern eine neue Weltwirtschaftsordnung. Auf die weltweite Hochkonjunktur ist eine scharfe und recht lange anhaltende Rezession gefolgt; aber noch immer dominieren inflationäre Tendenzen. Den Konjunktureinbruch überlagert hat die Vervielfachung des Ölpreises Ende 1973. Sie wurde von vielen Beobachtern als Beginn einer Phase mit zunehmendem Rohstoffmangel und nie gekannten Ungleichgewichten in den Zahlungsbilanzen gedeutet. Von den vielfach geäußerten Befürchtungen haben sich manche als übertrieben erwiesen; denn viele Schwierigkeiten konnte der Markt viel besser als erwartet und ziemlich geräuschlos bewältigen. Gleichwohl erscheint es geraten, die alten und die neuen Probleme der Weltwirtschaft ständig zu beobachten. Vom 23. -27. Juni, traf sich in Kiel eine Gruppe unabhängiger Ökonomen aus Japan, Nordamerika und der Europäischen Gemeinschaft in der Absicht, die Situation der Weltwirtschaft zu analysieren und Vorschläge für wirtschaftspolitische Maßnahmen auf nationaler und internationaler Ebene auszuarbeiten. Das Institut für Weltwirtschaft war Gastgeber. Das Kieler Symposium ist ein Glied in einer Reihe trilateraler Konferenzen über weltwirtschaftliche Fragen, die von der Brookings Institution in Washington, dem Japan Economic Research Center in Tokio und dem Institut für Weltwirtschaft gemeinsam veranstaltet werden. Die Ergebnisse werden jeweils in englischer, japanischer und deutscher Sprache veröffentlicht; frühere Berichte in der deutschen Fassung sind als Kieler Diskussionsbeiträge Nr. 31 "Welthandel und Strukturanpassung in den Industrieländern" und Nr. 36 "Weltrohstoffversorgung: Konflikt oder Kooperation?" erschienen. --

Enhanced Visual Temporal Resolution in Autism Spectrum Disorders

Cognitive functions that rely on accurate sequencing of events, such as action planning and execution, verbal and nonverbal communication, and social interaction rely on well-tuned coding of temporal event-structure. Visual temporal event-structure coding was tested in 17 high-functioning adolescents and adults with autism spectrum disorder (ASD) and mental- and chronological-age matched typically-developing (TD) individuals using a perceptual simultaneity paradigm. Visual simultaneity thresholds were lower in individuals with ASD compared to TD individuals, suggesting that autism may be characterised by increased parsing of temporal event-structure, with a decreased capability for integration over time. Lower perceptual simultaneity thresholds in ASD were also related to increased developmental communication difficulties. These results are linked to detail-focussed and local processing bias

Overview of the PALM model system 6.0

In this paper, we describe the PALM model system 6.0. PALM (formerly an abbreviation for Parallelized Largeeddy Simulation Model and now an independent name) is a Fortran-based code and has been applied for studying a variety of atmospheric and oceanic boundary layers for about 20 years. The model is optimized for use on massively parallel computer architectures. This is a follow-up paper to the PALM 4.0 model description in Maronga et al. (2015). During the last years, PALM has been significantly improved and now offers a variety of new components. In particular, much effort was made to enhance the model with components needed for applications in urban environments, like fully interactive land surface and radiation schemes, chemistry, and an indoor model. This paper serves as an overview paper of the PALM 6.0 model system and we describe its current model core. The individual components for urban applications, case studies, validation runs, and issues with suitable input data are presented and discussed in a series of companion papers in this special issue

Are social innovation paradigms incommensurable?

This paper calls attention to the problematic use of the concept of social innovation which remains undefined despite its proliferation throughout academic and policy discourses. Extant research has thus far failed to capture the socio-political contentions which surround social innovation. This paper therefore draws upon the work of Thomas Kuhn and conducts a paradigmatic analysis of the field of social innovation which identifies two emerging schools: one technocratic, the other democratic. The paper identifies some of the key thinkers in each paradigm and explains how the struggle between these two paradigms reveals itself to be part of a broader conflict between neoliberalism and it opponents and concludes by arguing that future research focused upon local contextualised struggles will reveal which paradigm is in the ascendancy