Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin resistance. DG is a precursor for phospholipids, thus phospholipid synthesis could be involved in regulating muscle DG. ...Little is known about the interaction between phospholipid and DG in muscle; therefore, we examined whether disrupting muscle phospholipid synthesis, specifically phosphatidylethanolamine (PtdEtn), would influence muscle DG content and insulin sensitivity. Muscle PtdEtn synthesis was disrupted by deleting CTP:phosphoethanolamine cytidylyltransferase (ECT), the rate-limiting enzyme in the CDP-ethanolamine pathway, a major route for PtdEtn production. While PtdEtn was reduced in muscle-specific ECT knockout mice, intramyocellular and membrane-associated DG was markedly increased. Importantly, however, this was not associated with insulin resistance. Unexpectedly, mitochondrial biogenesis and muscle oxidative capacity were increased in muscle-specific ECT knockout mice and were accompanied by enhanced exercise performance. These findings highlight the importance of the CDP-ethanolamine pathway in regulating muscle DG content and challenge the DG-induced insulin resistance hypothesis.
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•The CDP-ethanolamine pathway was eliminated from muscle•Muscle ECT deficiency altered phospholipid species and increased diacylglycerol•Insulin sensitivity was normal in mice lacking the CDP-ethanolamine pathway•ECT deficiency increased mitochondrial biogenesis and oxidative capacity
Accumulation of diacylglycerol (DAG), a phospholipid precursor, is associated with insulin resistance. Selathurai et al. show that eliminating the CDP-ethanolamine pathway in skeletal muscle causes DAG accumulation and alters membrane phospholipid composition. However, insulin sensitivity remains normal, and muscle mitochondrial content, oxidative capacity, and exercise performance are enhanced.
The Magnetospheric Multiscale mission has observed electron whistler waves at the center and at the edges of magnetic holes in the dayside magnetosheath. The magnetic holes are nonlinear mirror ...structures since their magnitude is anticorrelated with particle density. In this article, we examine the growth mechanisms of these whistler waves and their interaction with the host magnetic hole. In the observations, as magnetic holes develop and get deeper, an electron population gets trapped and develops a temperature anisotropy favorable for whistler waves to be generated. In addition, the decrease in magnetic field magnitude and the increase in density reduce the electron resonance energy, which promotes the electron cyclotron resonance. To investigate this process, we used expanding box particle-in-cell simulations to produce the mirror instability, which then evolve into magnetic holes. The simulation shows that whistler waves can be generated at the center and edges of magnetic holes, which reproduces the primary features of the MMS observations. The simulation shows that the electron temperature anisotropy develops in the center of the magnetic hole once the mirror instability reaches its nonlinear stage of evolution. The plasma is then unstable to whistler waves at the minimum of the magnetic field structures. In the saturation regime of mirror instability, when magnetic holes are developed, the electron temperature anisotropy appears at the edges of the holes and electron distributions become more isotropic at the magnetic field minimum. At the edges, the expansion of magnetic holes decelerates the electrons, which leads to temperature anisotropies.
Although recent studies provide evidence for a common genetic basis between complex traits and Mendelian disorders, a thorough quantification of their overlap in a phenotype-specific manner remains ...elusive. Here, we have quantified the overlap of genes identified through large-scale genome-wide association studies (GWASs) for 62 complex traits and diseases with genes containing mutations known to cause 20 broad categories of Mendelian disorders. We identified a significant enrichment of genes linked to phenotypically matched Mendelian disorders in GWAS gene sets; of the total 1,240 comparisons, a higher proportion of phenotypically matched or related pairs (n = 50 of 92 54%) than phenotypically unmatched pairs (n = 27 of 1,148 2%) demonstrated significant overlap, confirming a phenotype-specific enrichment pattern. Further, we observed elevated GWAS effect sizes near genes linked to phenotypically matched Mendelian disorders. Finally, we report examples of GWAS variants localized at the transcription start site or physically interacting with the promoters of genes linked to phenotypically matched Mendelian disorders. Our results are consistent with the hypothesis that genes that are disrupted in Mendelian disorders are dysregulated by non-coding variants in complex traits and demonstrate how leveraging findings from related Mendelian disorders and functional genomic datasets can prioritize genes that are putatively dysregulated by local and distal non-coding GWAS variants.
The Magnetospheric Multiscale (MMS) spacecraft encounter an electron diffusion region (EDR) of asymmetric magnetic reconnection at Earth's magnetopause. The EDR is characterized by agyrotropic ...electron velocity distributions on both sides of the neutral line. Various types of plasma waves are produced by the magnetic reconnection in and near the EDR. Here we report large-amplitude electron Bernstein waves (EBWs) at the electron-scale boundary of the Hall current reversal. The finite gyroradius effect of the outflow electrons generates the crescent-shaped agyrotropic electron distributions, which drive the EBWs. The EBWs propagate toward the central EDR. The amplitude of the EBWs is sufficiently large to thermalize and diffuse electrons around the EDR. The EBWs contribute to the cross-field diffusion of the electron-scale boundary of the Hall current reversal near the EDR.
Background
Four ongoing US public health surveillance studies gather information relevant to the prevalence, impact, and treatment of headache and migraine: the National Health Interview Survey, the ...National Health and Nutrition Examination Survey, the National Ambulatory Care Survey, and the National Hospital Ambulatory Medical Care Survey. The American Migraine Prevalence and Prevention (AMPP) study is a privately funded study that provides comparative US population‐based estimates of the prevalence and burden of migraine and chronic migraine.
Objective
To gather in one place and compare the most current available estimates of the US adult prevalence of headache and migraine, and the number of affected people overall and in various subgroups, and to provide estimates of headache burden and treatment patterns by examining migraine and headache as a reason for ambulatory care and emergency department (ED) visits in the United States.
Methods
We reviewed published analyses from available epidemiological studies identified through searches of PubMed and the National Center for Health Statistics. We aimed to identify information about migraine and headache burden, and treatment in national surveys conducted over the last decade. For each source, we selected the best available and most current estimate of migraine or headache prevalence, and selected associated measures of disability, health care use, and treatment patterns.
Results
Compared with a slightly higher proportion of 22.7% in the National Health and Nutrition Examination Survey, 16.6% of adults 18 or older reported having migraine or other severe headaches in the last 3 months in the 2011 National Health Interview Survey. In contrast, the AMPP study found an overall prevalence of migraine of 11.7% and probable migraine of 4.5%, for a total of 16.2%. Data from National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey showed that head pain was the fifth leading cause of ED visits overall in the US and accounted for 1.2% of outpatient visits. The burden of headache was highest in females 18‐44, where the 3‐month prevalence of migraine or severe headache was 26.1% and head pain was the third leading cause of ED visits. The prevalence and burden of headache was substantial even in the least affected subgroup of males 75 or older, where 4.6% reported experiencing severe headache or migraine in the previous 3 months. Triptans accounted for almost 80% of antimigraine analgesics prescribed at office visits in 2009, nearly half of which were for sumatriptan. Migraine is associated with increased risk for other physical and psychiatric comorbidities, and this risk increases with headache frequency.
Conclusion
This report provides the most current available estimates of the prevalence, impact, and treatment patterns of migraine or severe headache in the United States. Migraine and other severe headaches are a common and major public health problem, particularly among reproductive‐aged women. Data about prevalence and disability from the major government‐funded surveillance studies are generally consistent with results of studies such as the American Migraine Studies 1 and 2, and the AMPP study.
Purpose of Review
To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura.
Recent Findings
The ICHD-3 has recently ...refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe.
Summary
The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.
We investigate the accuracy with which the reconnection electric field EM can be determined from in situ plasma data. We study the magnetotail electron diffusion region observed by National ...Aeronautics and Space Administration's Magnetospheric Multiscale (MMS) on 11 July 2017 at 22:34 UT and focus on the very large errors in EM that result from errors in an LMN boundary normal coordinate system. We determine several LMN coordinates for this MMS event using several different methods. We use these M axes to estimate EM. We find some consensus that the reconnection rate was roughly EM = 3.2 ± 0.6 mV/m, which corresponds to a normalized reconnection rate of 0.18 ± 0.035. Minimum variance analysis of the electron velocity (MVA‐ve), MVA of E, minimization of Faraday residue, and an adjusted version of the maximum directional derivative of the magnetic field (MDD‐B) technique all produce reasonably similar coordinate axes. We use virtual MMS data from a particle‐in‐cell simulation of this event to estimate the errors in the coordinate axes and reconnection rate associated with MVA‐ve and MDD‐B. The L and M directions are most reliably determined by MVA‐ve when the spacecraft observes a clear electron jet reversal. When the magnetic field data have errors as small as 0.5% of the background field strength, the M direction obtained by MDD‐B technique may be off by as much as 35°. The normal direction is most accurately obtained by MDD‐B. Overall, we find that these techniques were able to identify EM from the virtual data within error bars ≥20%.
Key Points
The reconnection rate EM is estimated for one event using several techniques to find an M direction
The error bars in EM and the LMN coordinate directions are estimated from virtual data
The reconnection rate is likely EM = 3.2 mV/m ± 0.6 mV/m, which corresponds to a normalized rate of 0.18 ± 0.035
In the magnetosheath, intense whistler mode waves, called “Lion roars,” are often detected in troughs of magnetic field intensity in mirror mode structures. Using data obtained by the four ...Magnetospheric Multiscale (MMS) spacecraft, we show that reversals of gradient of magnetic field intensity along the magnetic field correspond to reversals of the field‐aligned component of Poynting flux of whistler mode waves in the troughs. Such a characteristic is consistent with the idea that the whistler mode waves are effectively generated near the local minima of magnetic field intensity because of the smallest cyclotron resonance velocity and propagate toward regions of larger magnetic field intensity along the magnetic field lines on both sides. We use the reversal of the Poynting flux as an indicator of wave source regions. In these regions, we find that pancake or an outer edge of butterfly electron distributions above ~100 eV are good candidates for wave generation. Unclear correlations of phase difference and amplitude variations of whistler mode waves in cases of ~40 km spacecraft separation indicate that a simple plane wave approximation with a constant amplitude is not valid at this spatial scale that is much smaller than the ion gyroradius. The whistler mode waves consist of small coherent wave packets from multiple sources with spatial scales smaller than tens of electron gyroradii transverse to the background magnetic field in a mirror mode structure.
Key Points
Whistler mode waves are generated near local minima of magnetic field intensity and propagate along field lines on both sides
Pancake or an outer edge of butterfly electron distributions above ~100 eV are good candidates for wave generation
The waves consist of many small coherent wave packets of tens of electron gyroradii perpendicular to magnetic fields
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