Diazepam-induced changes in sleep: Role of the α1 GABAA receptor subtype

Ligands acting at the benzodiazepine (BZ) site of γ-aminobutyric acid type A (GABAA) receptors currently are the most widely used hypnotics. BZs such as diazepam (Dz) potentiate GABAA receptor activation. To determine the GABAA receptor subtypes that mediate the hypnotic action of Dz wild-type mice and mice that harbor Dz-insensitive α1 GABAA receptors [α1 (H101R) mice] were compared. Sleep latency and the amount of sleep after Dz treatment were not affected by the point mutation. An initial reduction of rapid eye movement (REM) sleep also occurred equally in both genotypes. Furthermore, the Dz-induced changes in the sleep and waking electroencephalogram (EEG) spectra, the increase in power density above 21 Hz in non-REM sleep and waking, and the suppression of slow-wave activity (SWA; EEG power in the 0.75- to 4.0-Hz band) in non-REM sleep were present in both genotypes. Surprisingly, these effects were even more pronounced in α1(H101R) mice and sleep continuity was enhanced by Dz only in the mutants. Interestingly, Dz did not affect the initial surge of SWA at the transitions to sleep, indicating that the SWA-generating mechanisms are not impaired by the BZ. We conclude that the REM sleep inhibiting action of Dz and its effect on the EEG spectra in sleep and waking are mediated by GABAA receptors other than α1, i.e., α2, α3, or α5 GABAA receptors. Because α1 GABAA receptors mediate the sedative action of Dz, our results provide evidence that the hypnotic effect of Dz and its EEG “fingerprint” can be dissociated from its sedative action.

Brain lipids that induce sleep are novel modulators of 5-hydroxytrypamine receptors.

Amide derivatives of fatty acids were recently isolated from cerebrospinal fluid of sleep-deprived animals and found to induce sleep in rats. To determine which brain receptors might be sensitive to these novel neuromodulators, we tested them on a range of receptors expressed in Xenopus oocytes. cis-9,10-Octadecenamide (ODA) markedly potentiated the action of 5-hydroxytryptamine (5-HT) on 5-HT2A and 5-HT2C receptors, but this action was not shared by related compounds such as oleic acid and trans-9,10-octacenamide. ODA was active at concentrations as low as 1 nM. The saturated analog, octadecanamide, inhibited rather than potentiated 5-HT2C responses. ODA had either no effect or only weak effects on other receptors, including muscarinic cholinergic, metabotropic glutamate, GABA(A), N-methyl-D-asparate, or alpha-amino-3-hydroxy-5-methyl-4-isoxozolepropionic acid receptors. Modulation of 5-HT2 receptors by ODA and related lipids may represent a novel mechanism for regulation of receptors that activate G proteins and thereby play a role in alertness, sleep, and mood as well as disturbances of these states.

Promotion of sleep mediated by the A2a-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D2 in rats.

A 6-hr continuous infusion of 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine (CGS21680), a selective A2a-adenosine agonist, into the subarachnoid space underlying the ventral surface region of the rostral basal forebrain, which has been defined as the prostaglandin (PG) D2-sensitive sleep-promoting zone, at rates of 0.02, 0.2, 2.0, and 12 pmol/min increased slow-wave sleep (SWS) and paradoxical sleep (PS) in a dose-dependent manner up to 183% and 202% of their respective baseline levels. The increments produced by the infusion of CGS21680 at 0.2 and 2.0 pmol/min were totally diminished when the rats had been pretreated with an i.p. injection of (E)-1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF17837; 30 mg/kg of body weight), a selective A2-adenosine antagonist. In contrast, the infusion of N6-cyclohexyladenosine (CHA), a selective A1-adenosine agonist, at 2 pmol/min significantly suppressed SWS before causing an increase in SWS, and a decrease in PS was also markedly visible. Essentially the same effects of CGS21680 and CHA were observed when these compounds were administered to the parenchymal region of the rostral basal forebrain through chronically implanted microdialysis probes. Thus, we clearly showed that stimulation of A2a-adenosine receptors in the rostral basal forebrain promotes SWS and PS. Furthermore, i.p. injections of KF17837 at 30 and 100 mg/kg of body weight dose-dependently attenuated the magnitude of the SWS increase produced by the infusion of PGD2 into the subarachnoid space of the sleep-promoting zone, thus indicating that the A2a-adenosine receptors are crucial in the sleep-promoting process triggered by PGD2.

Morningness-eveningness and sleep habits among adolescents: age and gender differences

Previous research has indicated the need to use large samples in different cultural contexts in order to clarify age and gender differences on morningness-eveningness and sleep habits. The goal of our research was to study the relationship between morningness-eveningness and sleep habits in a large sample of 2,649 adolescents between 12 and 16 years. The Morningness- Eveningness Scale for Children and an adaptation of the School Sleep Habits Survey measures were used. Results indicated a greater tendency toward eveningness with age and higher eveningness in 13- and 14-year-old girls. Older adolescents claimed later rising time on weekends, later bedtime and shorter sleep length, and greater social jetlag, weekend rise time delay, and weekend bedtime delay. Girls reported earlier rising time on weekdays, later rising time on weekends, longer sleep length on weekends, and greater social jetlag and weekend rising time delay. Lastly, evening oriented adolescents claimed later rising time and bedtime, shorter sleep length on weekdays but longer sleep duration on weekends, and greater social jetlag, weekend rising time delay, and weekend bedtime delay.

Systematic investigation of projectile fragmentation using beams of unstable B and C isotopes

Background: Models describing nuclear fragmentation and fragmentation fission deliver important input for planning nuclear physics experiments and future radioactive ion beam facilities. These models are usually benchmarked against data from stable beam experiments. In the future, two-step fragmentation reactions with exotic nuclei as stepping stones are a promising tool for reaching the most neutron-rich nuclei, creating a need for models to describe also these reactions. Purpose: We want to extend the presently available data on fragmentation reactions towards the light exotic region on the nuclear chart. Furthermore, we want to improve the understanding of projectile fragmentation especially for unstable isotopes. Method: We have measured projectile fragments from (10,12-18C) and B10-15 isotopes colliding with a carbon target. These measurements were all performed within one experiment, which gives rise to a very consistent data set. We compare our data to model calculations. Results: One-proton removal cross sections with different final neutron numbers (1 pxn) for relativistic C-10,C-12-18 and B10-15 isotopes impinging on a carbon target. Comparing model calculations to the data, we find that the EPAX code is not able to describe the data satisfactorily. Using ABRABLA07 on the other hand, we find that the average excitation energy per abraded nucleon needs to be decreased from 27 MeV to 8.1 MeV. With that decrease ABRABLA07 describes the data surprisingly well. Conclusions: Extending the available data towards light unstable nuclei with a consistent set of new data has allowed a systematic investigation of the role of the excitation energy induced in projectile fragmentation. Most striking is the apparent mass dependence of the average excitation energy per abraded nucleon. Nevertheless, this parameter, which has been related to final-state interactions, requires further study.

15 Relative Truths: Poetry and Fragmentation

A collection of fifteen poems is presented that deals with mental fragmentation and the fluidity of meaning. The work is a contribution to contemporary poetry, and it cannot be aligned with a specific movement, neither is it a criticism of any previous works; it is generally reflective of postmodernist poetry and postmodern psychology.

Rural Development Trends and Land Use Policy in Colorado: Contributors to Habitat Fragmentation?

Fragmentation of wildlife habitat is a primary driver of global species decline. A major contributor to habitat fragmentation in the United States is rural residential development. Rural development in Colorado is occurring at rates far greater than the national average. Additionally, the lack of state-level planning control coupled with a lack of comprehensive, effective planning tools at the local level creates conditions that contribute to habitat fragmentation in many rural counties. Greater oversight and involvement in land use planning is needed by the state level to assist county governments. This study provides five recommendations to strengthen Colorado state land use policy in order to reduce habitat fragmentation.

Does land fragmentation affect farm performance? A case study from Brittany. Factor Markets Working Paper No. 40, April 2013

Agricultural land fragmentation is widespread and may affect farmers’ decisions and impact farm performance, either negatively or positively. The authors investigated this impact for the western region of Brittany, France, in 2007, regressing a set of performance indicators on a set of fragmentation descriptors. The performance indicators (production costs, yields, revenue, profitability, technical and scale efficiency) were calculated at the farm level using Farm Accountancy Data Network (FADN) data, while the fragmentation descriptors were calculated at the municipality level using data from the cartographic field pattern registry (RPG). The various fragmentation descriptors enabled the authors to account for not only the traditional number and average size of plots, but also their geographical scattering. They found that farms experienced higher costs of production, lower crop yields and lower profitability where land fragmentation (LF) was more pronounced. Total technical efficiency was not found to be significantly related to any of the municipality LF descriptors used, while scale efficiency was lower where the average distance to the nearest neighbouring plot was greater. Pure technical efficiency was found to be negatively related to the average number of plots in the municipality, with the unexpected result that it was also positively related to the average distance to the nearest neighbouring plot. By simulating the impact of hypothetical consolidation programmes on average pre-tax profits and wheat yield, the study also showed that the marginal benefits of reducing fragmentation may differ with respect to the improved LF dimension and the performance indicator considered. The analysis therefore shows that the measures of land fragmentation usually used in the literature do not reveal the full set of significant relationships with farm performance and that, in particular, measures accounting for distance should be considered more systematically.

The South Caucasus - Between integration and fragmentation

The South Caucasus is situated at the intersection of Eurasia’s major transport and energy corridors, making it an important geostrategic region. Traditional regional actors Iran, Turkey and Russia have jostled for influence and power in the region for centuries, and are now faced with competition from the EU, China, the US and NATO. Although Armenia, Azerbaijan and Georgia have been independent for more than two decades, they still continue to feel the sway, and sometimes threat, of external actors. As a response, the three South Caucasus states have chosen very different geostrategic paths since the collapse of the Soviet Union, leaving the region more fragmented and volatile than ever. In this book, various authors offer a deep and broad understanding of the developments in the South Caucasus, analyse the different foreign trajectories that each of the three state is following, and highlight the impact of external actors’ policies.

Addressing fragmentation in EU mobile telecom markets. Bruegel Policy Contribution ISSUE 2015/13, July 2015

- Mobile telecommunications markets are an important part of the European Commission’s strategy for the completion of the European Union Digital Single. The use of mobile telecommunications – particularly mobile data access – is growing and becoming an increasingly important input for the economy. - The EU currently does not have a unified mobile telecommunications market. The EU compares favourably to the United States in terms of prices and connection speed, but lags behind in terms of coverage of high-speed 4G wireless connections. -Europe’s long-term goal should be to make data access easier by increasing highspeed wireless coverage while keeping prices down for users. An increase in cross-border competition could help to achieve that goal. - The Commission has two important levers to help stimulate cross-border supply:(a) ensuring competition in intra-country mobile markets in order to provide an incentive for operators to expand into other jurisdictions, and (b) reducing mobile operators’ costs of expansion into multiple EU countries. The further development of policies on international roaming and radio spectrum management will be central to this effort.

Ribosome Shut-Down by 16S rRNA Fragmentation in Stationary-Phase Escherichia coli

Stationary-phase bacterial cells are characterized by vastly reduced metabolic activities yielding a dormant-like phenotype. Several hibernation programs ensure the establishment and maintenance of this resting growth state. Some of the stationary phase-specific modulations affect the ribosome and its translational activity directly. In stationary-phase Escherichia coli, we observed the appearance of a 16S rRNA fragmentation event at the tip of helix 6 within the small ribosomal subunit (30S). Stationary-phase 30S subunits showed markedly reduced activities in protein biosynthesis. On the other hand, the functional performance of stationary-phase large ribosomal subunits (50S) was indistinguishable from particles isolated from exponentially growing cells. Introduction of the 16S rRNA cut in vitro at helix 6 of exponential phase 30S subunits renders them less efficient in protein biosynthesis. This indicates that the helix 6 fragmentation is necessary and sufficient to attenuate translational activities of 30S ribosomal subunits. These results suggest that stationary phase-specific cleavage of 16S rRNA within the 30S subunit is an efficient means to reduce global translation activities under non-proliferating growth conditions.