Brain histaminergic neurons play a prominent role in arousal and maintenance of wakefulness (W). H(3)-receptors control the activity of histaminergic neurons through presynaptic autoinhibition. The ...role of H(3)-receptor antagonists/inverse agonists (H(3)R-antagonists) in the potential therapy of vigilance deficiency and sleep-wake disorders were studied by assessing their effects on the mouse cortical EEG and sleep-wake cycle in comparison to modafinil and classical psychostimulants. The H(3)R-antagonists, thioperamide and ciproxifan increased W and cortical EEG fast rhythms and, like modafinil, but unlike amphetamine and caffeine, their waking effects were not accompanied by sleep rebound. Conversely, imetit (H(3)R-agonist) enhanced slow wave sleep and dose-dependently attenuated ciproxifan-induced W, indicating that the effects of both ligands involve H(3)-receptor mechanisms. Additional studies using knockout (KO) mice confirmed the essential role of H(3)-receptors and histamine-mediated transmission in the wake properties of H(3)R-antagonists. Thus ciproxifan produced no increase in W in either histidine-decarboxylase (HDC, histamine-synthesizing enzyme) or H(1)- or H(3)-receptor KO-mice whereas its waking effects persisted in H(2)-receptor KO-mice. These data validate the hypothesis that H(3)R-antagonists, through disinhibition of H(3)-autoreceptors, enhancing synaptic histamine that in turn activates postsynaptic H(1)-receptors promoting W. Interestingly amphetamine and modafinil, despite their potent arousal effects, appear unlikely to depend on histaminergic mechanism as their effects still occurred in HDC KO-mice. The present study thus distinguishes two classes of wake-improving agents: the first acting through non-histaminergic mechanisms and the second acting via histamine and supports brain H(3)-receptors as potentially novel therapeutic targets for vigilance and sleep-wake disorders.
Treating hemodialysis patients to combat anemia corrects hemoglobin but exacerbates iron deficiency by utilizing iron stores. Patients needing iron should receive this by intravenous (i.v.) means. ...The Dialysis patients’ Response to IV iron with Elevated ferritin (DRIVE) trial investigated the role of i.v. iron in anemic patients with high ferritin, low transferrin saturation, and adequate epoetin doses. We examined whether baseline iron and inflammation markers predict the response of hemoglobin to treatment. Patients (134) were randomized to no added iron or to i.v. ferric gluconate for eight consecutive hemodialysis sessions spanning 6 weeks with epoetin increased by 25% in both groups. The patients started with hemoglobin less than or equal to 11g/dl, ferritin between 500 and 1200ng/ml, and transferrin saturation of less than 25%. Significantly, patients with a reticulocyte hemoglobin content greater than or equal to 31.2pg were over five times more likely to achieve a clinically significant increase in hemoglobin of greater than 2g/dl. Lower reticulocyte hemoglobin contents did not preclude a response to i.v. iron. Significantly higher transferrin saturation or lower C-reactive protein but not ferritin or soluble transferrin receptor levels predicted a greater response; however their influence was not clinically significant in either group. We conclude that none of the studied markers is a good predictor of response to anemia treatment in this patient sub-population.
Gamma-ray emission from a narrow band at the galactic equator has previously been detected up to 30 GeV. We report evidence for a TeV gamma-ray signal from a region of the galactic plane by Milagro, ...a large-field-of-view water Cherenkov detector for extensive air showers. An excess with a significance of 4.5 standard deviations has been observed from the region of galactic longitude l E (40 degrees, 100 degrees) and latitude /b/ < 5 degrees. Under the assumption of a simple power law spectrum, with no cutoff in the EGRET-Milagro energy range, the measured integral flux is phi gamma(>3.5 TeV) = (6.4 +/- 1.4 +/- 2.1) x 10(-11) cm(-2) s(-1) sr(-1). This flux is consistent with an extrapolation of the EGRET spectrum between 1 and 30 GeV in this galactic region.
The effect of endophytic
Beauveria bassiana in banana (
Musa spp.) plants against the banana weevil
Cosmopolites sordidus was examined in a screenhouse study in Uganda. Tissue-cultured banana plants ...(cv. Kibuzi, genome group EA-AAA) were inoculated by dipping roots in a
B. bassiana suspension of 1.5
×
10
7
conidia/ml for 2
h.
C. sordidus larvae were introduced 2 months later. Two weeks after larval infestation, endophytic
B. bassiana significantly reduced larval survivorship (23.5–88.9% mycosis), resulting in 42.0–86.7% reduction of plant damage. This study has demonstrated for the first time that endophytic
B. bassiana can be used to target the cryptic and damaging stage of
C. sordidus, and offers an alternative, effective delivery mechanism for this biological control agent.
This commentary discusses the benefits and limitations of cinacalcet use for posttransplant hypercalcemia and secondary hyperparathyroidism, alternative management options, and gaps in our evidence ...base. See article by Evenepoel et al on page 2545.
Mucosal malignant melanomas are uncommon. It is rare for a primary mucosal melanoma to occur in the anorectal region. Anorectal polypoid mucosal prolapse however, is a relatively common condition. We ...report a case of malignant melanoma presenting as mucosal prolapse and inducing changes similar to inflammatory cloacogenic polyp.
The two-stage vibration isolation and positioning platform provides passive and active isolation in all directions and translation. It uses a unique combination of position sensors, geophones and ...broadband seismometers to provide unprecedented levels of isolation.
•The paper presents the two-stage vibration isolation and positioning platform used in Advanced LIGO gravitational waves detectors.•The system can support a 1000kg of sensitive equipment and operate in ultra-high vacuum.•Each of the two stages provide passive and active isolation in all directions of translation and rotation (12 axis).•The active control strategy uses a unique combination of relative sensors, geophones and broadband seismometers.•The system reduces the motion to the level of 10−11 m/Hz at 1Hz and 10−12 m/Hz at 10Hz.
New generations of gravity wave detectors require unprecedented levels of vibration isolation. This paper presents the final design of the vibration isolation and positioning platform used in Advanced LIGO to support the interferometer's core optics. This five-ton two-and-half-m wide system operating in ultra-high vacuum. It features two stages of isolation mounted in series. The stages are imbricated to reduce the overall height. Each stage provides isolation in all directions of translation and rotation. The system is instrumented with a unique combination of low noise relative and inertial sensors. The active control provides isolation from 0.1Hz to 30Hz. It brings the platform motion down to 10−11 m/Hz at 1Hz. Active and passive isolation combine to bring the platform motion below 10−12 m/Hz at 10Hz. The passive isolation lowers the motion below 10−13 m/Hz at 100Hz. The paper describes how the platform has been engineered not only to meet the isolation requirements, but also to permit the construction, testing, and commissioning process of the fifteen units needed for Advanced LIGO observatories.
A new species of the genus Aporcella collected from a watermelon field in Nigeria is described, including its morphological and molecular (small subunit (SSU) and large subunit (LSU) ribosomal DNA ...(rDNA)) characterization. Aporcella femina sp. n. is distinguished by its 3.21–3.64 mm-long body, inner cuticle layer with fine but distinct transverse striation, lip region offset by deep constriction, 22–25 μm broad, odontostyle 20–26 μm, neck 661–811 μm long, pharyngeal expansion occupying 52–56% of the total neck length, female genital system didelphic–amphidelphic, uterus 191–350 μm or 1.9–3.3 mid-body diameters long, V = 52–57, tail short and convex conoid (35–48 μm, c = 72–98, c′ = 0.7–0.9) and males absent. Phylogenetic analyses based on the partial sequence of SSU and LSU (D2–D3) rDNA revealed a close relationship of A. femina sp. n. with other Aporcella species, confirming the monophyly of the genus as well as its association to a clade made of several taxa characterized by the absence of pars refringens vaginae.
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