211 research outputs found
Ion concentrations in cerebrospinal fluid in wakefulness, sleep and sleep deprivation in healthy humans
Sleep is controlled by a circadian rhythmicity, via a reduction of arousal-promoting neuromodulatory activity, and by accumulation of somnogenic factors in the interstitial fluid of the brain. Recent experiments in mice suggest that a reduced neuronal excitability caused by a reduced concentration of potassium in the brain, concomitant with an increased concentration of calcium and magnesium, constitutes an important mediator of sleep. In the present study, we examined whether such changes in ion concentrations could be detected in the cerebrospinal fluid of healthy humans. Each subject underwent cerebrospinal fluid collection at three occasions in a randomized order: at 15:00 hoursâ17:00 hours during waking, at 06:00 hoursâ07:00 hours immediately following 1 night of sleep, and at 06:00 hoursâ07:00 hours following 1 night of sleep deprivation. When compared with wakefulness, both sleep and sleep deprivation produced the same effect of a small (0.1Â mm, about 3%), but robust and highly significant, reduction in potassium concentration. Calcium and magnesium concentrations were unchanged. Our results support a circadian modulation of neuronal excitability in the brain mediated via changes of the interstitial potassium concentration
Beheersing van Rhizoctonia solani door verhoogde bodemweerbaarheid
In de afgelopen jaren is uitgebreid gezocht naar een methodiek die wel de ziektewering tegen Rhizoctonia betrouwbaar kan stimuleren. Hierbij is ontdekt dat de antagonistische bacteriegroep Lysobacter spp., die van nature in diverse Nederlandse gronden voorkomt, correleert met ziektewering. In 2012 zijn voor het eerst veldproeven uitgevoerd
Astrocyte-mediated short-term synaptic depression in the rat hippocampal CA1 area: two modes of decreasing release probability
<p>Abstract</p> <p>Background</p> <p>Synaptic burst activation feeds back as a short-term depression of release probability at hippocampal CA3-CA1 synapses. This short-term synaptic plasticity requires functional astrocytes and it affects both the recently active (< 1 s) synapses (post-burst depression) as well as inactive neighboring synapses (transient heterosynaptic depression). The aim of this study was to investigate and compare the components contributing to the depression of release probability in these two different scenarios.</p> <p>Results</p> <p>When tested using paired-pulses, following a period of inactivity, the transient heterosynaptic depression was expressed as a reduction in the response to only the first pulse, whereas the response to the second pulse was unaffected. This selective depression of only the first response in a high-frequency burst was shared by the homosynaptic post-burst depression, but it was partially counteracted by augmentation at these recently active synapses. In addition, the expression of the homosynaptic post-burst depression included an astrocyte-mediated reduction of the pool of release-ready primed vesicles.</p> <p>Conclusions</p> <p>Our results suggest that activated astrocytes depress the release probability via two different mechanisms; by depression of vesicular release probability only at inactive synapses and by imposing a delay in the recovery of the primed pool of vesicles following depletion. These mechanisms restrict the expression of the astrocyte-mediated depression to temporal windows that are typical for synaptic burst activity.</p
Capture of exocomets and the erosion of the Oort cloud due to stellar encounters in the Galaxy
Stars and planetary system
Oligonucleotides Targeting DNA Repeats Downregulate Huntingtin Gene Expression in Huntington's Patient-Derived Neural Model System
Huntington's disease (HD) is one of the most common, dominantly inherited neurodegenerative disorders. It affects the striatum, cerebral cortex, and other subcortical structures leading to involuntary movement abnormalities, emotional disturbances, and cognitive impairments. HD is caused by a CAGâąCTG trinucleotide-repeat expansion in exon 1 of the huntingtin (HTT) gene leading to the formation of mutant HTT (mtHTT) protein aggregates. Besides the toxicity of the mutated protein, there is also evidence that mtHTT transcripts contribute to the disease. Thus, the reduction of both mutated mRNA and protein would be most beneficial as a treatment. Previously, we designed a novel anti-gene oligonucleotide (AGO)-based strategy directly targeting the HTT trinucleotide-repeats in DNA and reported downregulation of mRNA and protein in HD patient fibroblasts. In this study, we differentiate HD patient-derived induced pluripotent stem cells to investigate the efficacy of the AGO, a DNA/Locked Nucleic Acid mixmer with phosphorothioate backbone, to modulate HTT transcription during neural in vitro development. For the first time, we demonstrate downregulation of HTT mRNA following both naked and magnetofected delivery into neural stem cells (NSCs) and show that neither emergence of neural rosette structures nor self-renewal of NSCs is compromised. Furthermore, the inhibition potency of both HTT mRNA and protein without off-target effects is confirmed in neurons. These results further validate an anti-gene approach for the treatment of HD
Optical to near-infrared transit observations of super-Earth GJ1214b: water-world or mini-Neptune?
GJ1214b is thought to be either a mini-Neptune with a thick, hydrogen-rich
atmosphere, or a planet with a composition dominated by water. In the case of a
hydrogen-rich atmosphere, molecular absorption and scattering processes may
result in detectable radius variations as a function of wavelength. The aim of
this paper is to measure these variations. We have obtained observations of the
transit of GJ1214b in the r- and I-band with the INT, in the g, r, i and z
bands with the 2.2 meter MPI/ESO telescope, in the Ks-band with the NOT, and in
the Kc-band with the WHT. By comparing the transit depth between the the
different bands, which is a measure for the planet-to-star size ratio, the
atmosphere is investigated. We do not detect clearly significant variations in
the planet-to-star size ratio as function of wavelength. Although the ratio at
the shortest measured wavelength, in g-band, is 2sigma larger than in the other
bands. The uncertainties in the Ks and Kc bands are large, due to systematic
features in the light curves. The tentative increase in the planet-to-star size
ratio at the shortest wavelength could be a sign of an increase in the
effective planet-size due to Rayleigh scattering, which would require GJ1214b
to have a hydrogen-rich atmosphere. If true, then the atmosphere has to have
both clouds, to suppress planet-size variations at red optical wavelengths, as
well as a sub-solar metallicity, to suppress strong molecular features in the
near- and mid-infrared. However, star spots, which are known to be present on
the hoststar's surface, can (partly) cancel out the expected variations in
planet-to-star size ratio, due to the lower surface temperature of the spots .
A hypothetical spot-fraction of 10% would be able to raise the infrared points
sufficiently with respect to the optical measurements to be inconsistent with a
water-dominated atmosphere. [abridged]Comment: 13 pages, 8 figures. Accepted for publication in A&
A genetically encoded reporter of synaptic activity in vivo
To image synaptic activity within neural circuits, we tethered the genetically encoded calcium indicator (GECI) GCaMP2 to synaptic vesicles by fusion to synaptophysin. The resulting reporter, SyGCaMP2, detected the electrical activity of neurons with two advantages over existing cytoplasmic GECIs: it identified the locations of synapses and had a linear response over a wider range of spike frequencies. Simulations and experimental measurements indicated that linearity arises because SyGCaMP2 samples the brief calcium transient passing through the presynaptic compartment close to voltage-sensitive calcium channels rather than changes in bulk calcium concentration. In vivo imaging in zebrafish demonstrated that SyGCaMP2 can assess electrical activity in conventional synapses of spiking neurons in the optic tectum and graded voltage signals transmitted by ribbon synapses of retinal bipolar cells. Localizing a GECI to synaptic terminals provides a strategy for monitoring activity across large groups of neurons at the level of individual synapses
A pilot randomized controlled trial of exercise to improve cognitive performance in patients with stable glioma:A proof of concept
BACKGROUND: Patients with glioma often suffer from cognitive deficits. Physical exercise has been effective in ameliorating cognitive deficits in older adults and neurological patients. This pilot randomized controlled trial (RCT) explored the possible impact of an exercise intervention, designed to improve cognitive functioning in glioma patients, regarding cognitive test performance and patient-reported outcomes (PROs). METHODS: Thirty-four clinically stable patients with World Health Organization grades II/III glioma were randomized to a home-based remotely coached exercise group or an active control group. Patients exercised 3 times per week for 20-45 minutes, with moderate to vigorous intensity, during 6 months. At baseline and immediate follow-up, cognitive performance and PROs were assessed with neuropsychological tests and questionnaires, respectively. Linear regression analyses were used to estimate effect sizes of potential between-group differences in cognitive performance and PROs at 6 months. RESULTS: The exercise group (n = 21) had small- to medium-sized better follow-up scores than the control group (n = 11) on several measures of attention and information processing speed, verbal memory, and executive function, whereas the control group showed a slightly better score on a measure of sustained selective attention. The exercise group also demonstrated small- to medium-sized better outcomes on measures of self-reported cognitive symptoms, fatigue, sleep, mood, and mental health-related quality of life. CONCLUSIONS: This small exploratory RCT in glioma patients provides a proof of concept with respect to improvement of cognitive functioning and PROs after aerobic exercise, and warrants larger exercise trials in brain tumor patients
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