2,235 research outputs found
Casein kinase iδ mutations in familial migraine and advanced sleep phase.
Migraine is a common disabling disorder with a significant genetic component, characterized by severe headache and often accompanied by nausea, vomiting, and light sensitivity. We identified two families, each with a distinct missense mutation in the gene encoding casein kinase Iδ (CKIδ), in which the mutation cosegregated with both the presence of migraine and advanced sleep phase. The resulting alterations (T44A and H46R) occurred in the conserved catalytic domain of CKIδ, where they caused reduced enzyme activity. Mice engineered to carry the CKIδ-T44A allele were more sensitive to pain after treatment with the migraine trigger nitroglycerin. CKIδ-T44A mice also exhibited a reduced threshold for cortical spreading depression (believed to be the physiological analog of migraine aura) and greater arterial dilation during cortical spreading depression. Astrocytes from CKIδ-T44A mice showed increased spontaneous and evoked calcium signaling. These genetic, cellular, physiological, and behavioral analyses suggest that decreases in CKIδ activity can contribute to the pathogenesis of migraine
To what extent do water reuse treatments reduce antibiotic resistance indicators? A comparison of two full-scale systems
Water reuse is an essential strategy for reducing water demand from conventional sources, alleviating water stress, and promoting sustainability, but understanding the effectiveness of associated treatment processes as barriers to the spread of antibiotic resistance is an important consideration to protecting human health. We comprehensively evaluated the reduction of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in two field-operational water reuse systems with distinct treatment trains, one producing water for indirect potable reuse (ozone/biologically-active carbon/granular activated carbon) and the other for non-potable reuse (denitrification-filtration/chlorination) using metagenomic sequencing and culture. Relative abundances of total ARGs/clinically-relevant ARGs and cultured ARB were reduced by several logs during primary and secondary stages of wastewater treatment, but to a lesser extent during the tertiary water reuse treatments. In particular, ozonation tended to enrich multi-drug ARGs. The effect of chlorination was facility-dependent, increasing the relative abundance of ARGs when following biologically-active carbon filters, but generally providing a benefit in reduced bacterial numbers and ecological and human health resistome risk scores. Relative abundances of total ARGs and resistome risk scores were lowest in aquifer samples, although resistant Escherichia coli and Klebsiella pneumoniae were occasionally detected in the monitoring well 3-days downgradient from injection, but not 6-months downgradient. Resistant E. coli and Pseudomonas aeruginosa were occasionally detected in the nonpotable reuse distribution system, along with increased levels of multidrug, sulfonamide, phenicol, and aminoglycoside ARGs. This study illuminates specific vulnerabilities of water reuse systems to persistence, selection, and growth of ARGs and ARB and emphasizes the role of multiple treatment barriers, including aquifers and distribution systems
Pegasus V -- a newly discovered ultra-faint dwarf galaxy on the outskirts of Andromeda
We report the discovery of an ultra-faint dwarf in the constellation of
Pegasus. Pegasus~V (Peg~V) was initially identified in the public imaging data
release of the DESI Legacy Imaging Surveys and confirmed with deep imaging from
Gemini/GMOS-N. The colour-magnitude diagram shows a sparse red giant branch
(RGB) population and a strong over-density of blue horizontal branch stars. We
measure a distance to Peg~V of ~kpc, making it a distant
satellite of Andromeda with and a half-light radius of ~pc. It is located ~kpc from Andromeda in the outskirts
of its halo. The RGB is well-fit by a metal-poor isochrone with [Fe/H],
suggesting it is very metal poor. This, combined with its blue horizontal
branch could imply that it is a reionisation fossil. This is the first
detection of an ultra-faint dwarf outside the deep Pan-Andromeda Archaeological
Survey area, and points to a rich, faint satellite population in the outskirts
of our nearest neighbour.Comment: Submitted to MNRAS Letters. 6 pages, 4 figures. Comments welcom
Pisces VII: Discovery of a possible satellite of Messier 33 in the DESI Legacy Imaging Surveys
We report deep imaging observations with DOLoRes@TNG of an ultra-faint dwarf
satellite candidate of the Triangulum galaxy (M33) found by visual inspection
of the public imaging data release of the DESI Legacy Imaging Surveys. Pisces
VII/Triangulum (Tri) III is found at a projected distance of 72 kpc from M33,
and using the tip of the red giant branch method we estimate a distance of
D=1.0 +0.3,-0.2 Mpc, meaning the galaxy could either be an isolated ultra-faint
or the second known satellite of M33. We estimate an absolute magnitude of
M_V=-6.1+/-0.2 if Pisces VII/Tri II is at the distance of M33, or as bright as
M_V=-6.8+/-0.2 if the galaxy is isolated. At the isolated distance, it has a
physical half-light radius of r_h=131+/-61 pc consistent with similarly faint
galaxies around the Milky Way. As the tip of the red giant branch is sparsely
populated, constraining a precision distance is not possible, but if Pisces
VII/Tri III can be confirmed as a true satellite of M33 it is a significant
finding. With only one potential satellite detected around M33 previously
(Andromeda XXII/Tri I), it lacks a significant satellite population in stark
contrast to the similarly massive Large Magellanic Cloud. The detection of more
satellites in the outskirts of M33 could help to better illuminate if this
discrepancy between expectation and observations is due to a poor understanding
of the galaxy formation process, or if it is due to the low luminosity and
surface brightness of the M33 satellite population which has thus far fallen
below the detection limits of previous surveys. If it is truly isolated, it
would be the faintest known field dwarf detected to date.Comment: 10 pages, 9 figures, 2 tables, accepted for publication in MNRAS.
This final version includes a moderate revision after the referee's comments
and a correct titl
Adaptation of Microelectrode Array Technology for the Study of Anesthesia-Induced Neurotoxicity in the Intact Piglet Brain
Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain.
This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the mechanism(s) of anesthesia-induced neurotoxicity (AIN). MEAs enable real-time monitoring of in vivo neurotransmitter activity and offer exceptional temporal and spatial resolution. It is hypothesized that anesthetic neurotoxicity is caused in part by glutamate dysregulation and MEAs offer a method to measure glutamate. The novel implementation of MEA technology in a piglet model presents a unique opportunity for the study of AIN
Controlling a spillover pathway with the molecular cork effect
Spillover of reactants from one active site to another is important in heterogeneous catalysis and has recently been shown to enhance hydrogen storage in a variety of materials. The spillover of hydrogen is notoriously hard to detect or control. We report herein that the hydrogen spillover pathway on a Pd/Cu alloy can be controlled by reversible adsorption of a spectator molecule. Pd atoms in the Cu surface serve as hydrogen dissociation sites from which H atoms can spillover onto surrounding Cu regions. Selective adsorption of CO at these atomic Pd sites is shown to either prevent the uptake of hydrogen on, or inhibit its desorption from, the surface. In this way, the hydrogen coverage on the whole surface can be controlled by molecular adsorption at a minority site, which we term a ‘molecular cork’ effect. We show that the molecular cork effect is present during a surface catalysed hydrogenation reaction and illustrate how it can be used as a method for controlling uptake and release of hydrogen in a model storage syste
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