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Signs of an inflammatory process, in particular increased pro-inflammatory cytokines and increased levels of prostaglandine E 2 (PGE 2 ), have repeatedly been described in major depression (MD). As cyclooxygenase-2 (COX-2) inhibitors inhibit the PGE 2 production and the production of pro-inflammatory cytokines, we performed a therapeutic trial with the COX-2 inhibitor celecoxib. In a prospective, double-blind, add-on study, 40 patients suffering from an acute depressive episode were randomly assigned to either reboxetine and celecoxib or to reboxetine plus placebo. After a wash-out period, 20 patients received 4–10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks. The treatment effect was calculated by analysis of variance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels. Over 6 weeks, both groups of patients showed significant improvement in scores of the Hamilton Depression Scale. However, the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group. Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology. Moreover, the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder, although the exact mechanisms remain to become elucidated.

In joint action literature it is often assumed that acting together is driven by pervasive and automatic process of co-representation, that is, representing the co-actor’s part of the task in addition to one’s own. Much of this research employs joint stimulus-response compatibility tasks varying the stimuli employed or the physical and social relations between participants. In this study we test the robustness of co-representation effects by focusing instead on variation in response modality. Specifically, we implement a mouse-tracking version of a Joint Simon Task in which participants respond by producing continuous movements with a computer mouse rather than pushing discrete buttons. We have three key findings. First, in a replication of an earlier study we show that in a classical individual Simon Task movement trajectories show greater curvature on incongruent trials, paralleling longer response times. Second, this effect largely disappears in a Go-NoGo Simon Task, in which participants respond to only one of the cues and refrain from responding to the other. Third, contrary to previous studies that use button pressing responses, we observe no overall effect in the joint variants of the task. However, we also detect a notable diversity in movement strategies adopted by the participants, with some participants showing the effect on the individual level. Our study casts doubt on the pervasiveness of co-representation, highlights the usefulness of mouse-tracking methodology and emphasizes the need for looking at individual variation in task performance.

Sodium intake is undoubtedly indispensable for normal body functions but can be detrimental when taken in excess of dietary requirements. The consequences of excessive salt intake are becoming increasingly clear as high salt consumption persists across the globe. Salt has long been suspected to promote the development of hypertension and cardiovascular diseases and is now also recognized as a potential modulator of inflammatory and autoimmune diseases through its direct and indirect effects on immune cells. The finding that, in addition to the kidneys, other organs such as the skin regulate sodium levels in the body prompted new hypotheses, including the concept that skin-resident macrophages might participate in tissue sodium regulation through their interactions with lymphatic vessels. Moreover, immune cells such as macrophages and different T cell subsets are found in sodium-rich interstitial microenvironments, where sodium levels modulate their function. Alterations to the intestinal bacterial community induced by excess dietary salt represent another relevant axis whereby salt indirectly modulates immune cell function. Depending on the inflammatory context, sodium might either contribute to protective immunity (for example, by enhancing host responses against cutaneous pathogens) or it might contribute to immune dysregulation and promote the development of cardiovascular and autoimmune diseases.

Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter-driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.

To explore the molecular profile and its prognostic implication in systemic mastocytosis (SM), we analyzed the mutation status of granulocyte–macrophage colony-forming progenitor cells (CFU-GM) in patients with KIT D816V + indolent SM (ISM, n =4), smoldering SM (SSM, n =2), aggressive SM (ASM, n =1), SM with associated clonal hematologic non-mast cell lineage disorder (SM-AHNMD, n =5) and ASM-AHNMD ( n =7). All patients with (A)SM-AHNMD ( n =12) carried 1–4 (median 3) additional mutations in 11 genes tested, most frequently TET2 , SRSF2 , ASXL1 , CBL and EZH2 . In multi-mutated (A)SM-AHNMD, KIT D816V + single-cell-derived CFU-GM colonies were identified in 8/12 patients (median 60%, range 0–95). Additional mutations were identified in CFU-GM colonies in all patients, and logical hierarchy analysis indicated that mutations in TET2 , SRSF2 and ASXL1 preceded KIT D816V. In ISM/SSM, no additional mutations were detected and CFU-GM colonies were exclusively KIT D816V − . These data indicate that (a) (A)SM-AHNMD is a multi-mutated neoplasm, (b) mutations in TET2 , SRSF2 or ASXL1 precede KIT D816V in ASM-AHNMD, (c) KIT D816V is thus a phenotype modifier toward SM and (d) KIT D816V or other mutations are rare in CFU-GM colonies of ISM/SSM patients, which might explain at least in part their better prognosis.

The Heat Flow and Physical Properties Package HP 3 for the InSight mission will attempt the first measurement of the planetary heat flow of Mars. The data will be taken at the InSight landing site in Elysium planitia (136  ∘ E, 5  ∘ N) and the uncertainty of the measurement aimed for shall be better than ±5 mW m −2 . The package consists of a mechanical hammering device called the “Mole” for penetrating into the regolith, an instrumented tether which the Mole pulls into the ground, a fixed radiometer to determine the surface brightness temperature and an electronic box. The Mole and the tether are housed in a support structure before being deployed. The tether is equipped with 14 platinum resistance temperature sensors to measure temperature differences with a 1- σ uncertainty of 6.5 mK. Depth is determined by a tether length measurement device that monitors the amount of tether extracted from the support structure and a tiltmeter that measures the angle of the Mole axis to the local gravity vector. The Mole includes temperature sensors and heaters to measure the regolith thermal conductivity to better than 3.5% (1- σ ) using the Mole as a modified line heat source. The Mole is planned to advance at least 3 m—sufficiently deep to reduce errors from daily surface temperature forcings—and up to 5 m into the martian regolith. After landing, HP 3 will be deployed onto the martian surface by a robotic arm after choosing an instrument placement site that minimizes disturbances from shadows caused by the lander and the seismometer. The Mole will then execute hammering cycles, advancing 50 cm into the subsurface at a time, followed by a cooldown period of at least 48 h to allow heat built up during hammering to dissipate. After an equilibrated thermal state has been reached, a thermal conductivity measurement is executed for 24 h. This cycle is repeated until the final depth of 5 m is reached or further progress becomes impossible. The subsequent monitoring phase consists of hourly temperature measurements and lasts until the end of the mission. Model calculations show that the duration of temperature measurement required to sufficiently reduce the error introduced by annual surface temperature forcings is 0.6 martian years for a final depth of 3 m and 0.1 martian years for the target depth of 5 m.

Background. The German National Health Interview and Examination Survey (GHS) is the first government mandated nationwide study to investigate jointly the prevalence of somatic and mental disorders within one study in the general adult population in Germany. This paper reports results from its Mental Health Supplement (GHS-MHS) on 4-week 12-month, and selected lifetime prevalence of a broad range of DSM-IV mental disorders, their co-morbidity and correlates in the community. Methods. The sample of the GHS-MHS (n=4181; multistage stratified random sample drawn from population registries; conditional response rate: 87·6%) can be regarded as representative for the German population aged 18–65. Diagnoses are based on fully structured computer assisted clinical interviews (M-CIDI), conducted by clinically trained interviewers. Results. 12-month prevalence for any DSM-IV study disorder is 31% (lifetime: 43%; 4-week: 20%) with anxiety disorders, mood disorders and somatoform syndromes being the most frequent diagnoses. Retrospective age of onset information reveals that most disorders begin early in life. Co-morbidity rates among mental disorders range from 44% to 94%. Correlates of increased rates of mental disorders and co-morbidity were: female gender (except for substance disorders), not being married, low social class, and poor somatic health status. Health care utilization for mental disorders depended on co-morbidity (30% in ‘pure’, 76% in highly co-morbid cases) and varied from 33% for substance use disorders to 75% for panic disorder. Conclusions. Results confirm and extend results from other national studies using the same assessment instruments with regard to prevalence, co-morbidity and sociodemographic correlates, covering a broader range of DSM-IV disorders [i.e. somatoform disorders, all anxiety disorders (except PTSD), mental disorders due to substance or general medical factor, eating disorders]. Intervention rates were higher than in previous studies, yet still low overall.

Ocean acidification substantially alters ocean carbon chemistry and hence pH but the effects on sea ice formation and the CO2 concentration in the enclosed brine channels are unknown. Microbial communities inhabiting sea ice ecosystems currently contribute 10-50% of the annual primary production of polar seas, supporting overwintering zooplankton species, especially Antarctic krill, and seeding spring phytoplankton blooms. Ocean acidification is occurring in all surface waters but the strongest effects will be experienced in polar ecosystems with significant effects on all trophic levels. Brine algae collected from McMurdo Sound (Antarctica) sea ice was incubated in situ under various carbonate chemistry conditions. The carbon chemistry was manipulated with acid, bicarbonate and bases to produce a pCO2 and pH range from 238 to 6066 µatm and 7.19 to 8.66, respectively. Elevated pCO2 positively affected the growth rate of the brine algal community, dominated by the unique ice dinoflagellate, Polarella glacialis. Growth rates were significantly reduced when pH dropped below 7.6. However, when the pH was held constant and the pCO2 increased, growth rates of the brine algae increased by more than 20% and showed no decline at pCO2 values more than five times current ambient levels. We suggest that projected increases in seawater pCO2, associated with OA, will not adversely impact brine algal communities.

This study aims to compare impacts of climate change on streamflow in four large representative African river basins: the Niger, the Upper Blue Nile, the Oubangui and the Limpopo. We set up the eco-hydrological model SWIM (Soil and Water Integrated Model) for all four basins individually. The validation of the models for four basins shows results from adequate to very good, depending on the quality and availability of input and calibration data. For the climate impact assessment, we drive the model with outputs of five bias corrected Earth system models of Coupled Model Intercomparison Project Phase 5 (CMIP5) for the representative concentration pathways (RCPs) 2.6 and 8.5. This climate input is put into the context of climate trends of the whole African continent and compared to a CMIP5 ensemble of 19 models in order to test their representativeness. Subsequently, we compare the trends in mean discharges, seasonality and hydrological extremes in the 21st century. The uncertainty of results for all basins is high. Still, climate change impact is clearly visible for mean discharges but also for extremes in high and low flows. The uncertainty of the projections is the lowest in the Upper Blue Nile, where an increase in streamflow is most likely. In the Niger and the Limpopo basins, the magnitude of trends in both directions is high and has a wide range of uncertainty. In the Oubangui, impacts are the least significant. Our results confirm partly the findings of previous continental impact analyses for Africa. However, contradictory to these studies we find a tendency for increased streamflows in three of the four basins (not for the Oubangui). Guided by these results, we argue for attention to the possible risks of increasing high flows in the face of the dominant water scarcity in Africa. In conclusion, the study shows that impact intercomparisons have added value to the adaptation discussion and may be used for setting up adaptation plans in the context of a holistic approach.

Ghrelin regulates energy homeostasis in various species and enhances memory in rodent models. In humans, the role of ghrelin in cognitive processes has yet to be characterized. Here we show in a double-blind randomized crossover design that acute administration of ghrelin alters encoding-related brain activity, however does not enhance memory formation in humans. Twenty-one healthy young male participants had to memorize food- and non-food-related words presented on a background of a virtual navigational route while undergoing fMRI recordings. After acute ghrelin administration, we observed decreased post-encoding resting state fMRI connectivity between the caudate nucleus and the insula, amygdala, and orbitofrontal cortex. In addition, brain activity related to subsequent memory performance was modulated by ghrelin. On the next day, however, no differences were found in free word recall or cued location-word association recall between conditions; and ghrelin's effects on brain activity or functional connectivity were unrelated to memory performance. Further, ghrelin had no effect on a cognitive test battery comprising tests for working memory, fluid reasoning, creativity, mental speed, and attention. In conclusion, in contrast to studies with animal models, we did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans. •Effects of ghrelin on memory for food-related words-location associations were tested.•Functional connectivity during post-encoding rest was altered after ghrelin injection.•Acute ghrelin administration had no behavioral effects on long-term memory retention.•Acute ghrelin administration had no behavioral effects on several other cognitive tasks.•Ghrelin's effects on memory markedly differ between animal models and human subjects.