Abstract
Interpretations of exoplanetary transmission spectra have been undermined by apparent obscuration due to clouds/hazes. Debate rages on whether weak H2O features seen in exoplanet spectra are ...due to clouds or inherently depleted oxygen. Assertions of solar H2O abundances have relied on making a priori model assumptions, for example, chemical/radiative equilibrium. In this work, we attempt to address this problem with a new retrieval paradigm for transmission spectra. We introduce poseidon, a two-dimensional atmospheric retrieval algorithm including generalized inhomogeneous clouds. We demonstrate that this prescription allows one to break vital degeneracies between clouds and prominent molecular abundances. We apply poseidon to the best transmission spectrum presently available, for the hot Jupiter HD 209458b, uncovering new insights into its atmosphere at the day–night terminator. We extensively explore the parameter space with an unprecedented 108 models, spanning the continuum from fully cloudy to cloud-free atmospheres, in a fully Bayesian retrieval framework. We report the first detection of nitrogen chemistry (NH3 and/or HCN) in an exoplanet atmosphere at 3.7–7.7σ confidence, non-uniform cloud coverage at 4.5–5.4σ, high-altitude hazes at >3σ and sub-solar H2O at ≳3–5σ, depending on the assumed cloud distribution. We detect NH3 at 3.3σ, and 4.9σ for fully cloudy and cloud-free scenarios, respectively. For the model with the highest Bayesian evidence, we constrain H2O at 5–15 ppm (0.01–0.03) × solar and NH3 at 0.01–2.7 ppm, strongly suggesting disequilibrium chemistry and cautioning against equilibrium assumptions. Our results herald a new promise for retrieving cloudy atmospheres using high-precision Hubble Space Telescope and James Webb Space Telescope spectra.
Purpose of Review
PTSD in youth is common and debilitating. In contrast to adult PTSD, relatively little is known about the neurobiology of pediatric PTSD, nor how neurodevelopment may be altered. ...This review summarizes recent neuroimaging studies in pediatric PTSD and discusses implications for future study.
Recent Findings
Pediatric PTSD is characterized by abnormal structure and function in neural circuitry supporting threat processing and emotion regulation. Furthermore, cross-sectional studies suggest that youth with PTSD have abnormal frontolimbic development compared to typically developing youth. Examples include declining hippocampal volume, increasing amygdala reactivity, and declining amygdala-prefrontal coupling with age.
Summary
Pediatric PTSD is characterized by both overt and developmental abnormalities in frontolimbic circuitry. Notably, abnormal frontolimbic development may contribute to increasing threat reactivity and weaker emotion regulation as youth age. Longitudinal studies of pediatric PTSD are needed to characterize individual outcomes and determine whether current treatments are capable of restoring healthy neurodevelopment.
Engram cells retain memory under retrograde amnesia Ryan, Tomás J.; Roy, Dheeraj S.; Pignatelli, Michele ...
Science (American Association for the Advancement of Science),
05/2015, Letnik:
348, Številka:
6238
Journal Article
Recenzirano
Odprti dostop
Memory consolidation is the process by which a newly formed and unstable memory transforms into a stable long-term memory. It is unknown whether the process of memory consolidation occurs exclusively ...through the stabilization of memory engrams. By using learning-dependent cell labeling, we identified an increase of synaptic strength and dendritic spine density specifically in consolidated memory engram cells. Although these properties are lacking in engram cells under protein synthesis inhibitor-induced amnesia, direct optogenetic activation of these cells results in memory retrieval, and this correlates with retained engram cell-specific connectivity. We propose that a specific pattern of connectivity of engram cells may be crucial for memory information storage and that strengthened synapses in these cells critically contribute to the memory retrieval process.
Mitochondria are quantifiably the most important sources of superoxide (O2●−) and hydrogen peroxide (H2O2) in mammalian cells. The overproduction of these molecules has been studied mostly in the ...contexts of the pathogenesis of human diseases and aging. However, controlled bursts in mitochondrial ROS production, most notably H2O2, also plays a vital role in the transmission of cellular information. Striking a balance between utilizing H2O2 in second messaging whilst avoiding its deleterious effects requires the use of sophisticated feedback control and H2O2 degrading mechanisms. Mitochondria are enriched with H2O2 degrading enzymes to desensitize redox signals. These organelles also use a series of negative feedback loops, such as proton leaks or protein S-glutathionylation, to inhibit H2O2 production. Understanding how mitochondria produce ROS is also important for comprehending how these organelles use H2O2 in eustress signaling. Indeed, twelve different enzymes associated with nutrient metabolism and oxidative phosphorylation (OXPHOS) can serve as important ROS sources. This includes several flavoproteins and respiratory complexes I-III. Progress in understanding how mitochondria generate H2O2 for signaling must also account for critical physiological factors that strongly influence ROS production, such as sex differences and genetic variances in genes encoding antioxidants and proteins involved in mitochondrial bioenergetics. In the present review, I provide an updated view on how mitochondria budget cellular H2O2 production. These discussions will focus on the potential addition of two acyl-CoA dehydrogenases to the list of ROS generators and the impact of important phenotypic and physiological factors such as tissue type, mouse strain, and sex on production by these individual sites.
For over 40 years, mitochondrial reactive oxygen species (ROS) production and balance has been studied in the context of oxidative distress and tissue damage. However, research over the past decade ...has demonstrated that the mitochondria have a more complicated relationship with ROS. Superoxide (O2•−) and hydrogen peroxide (H2O2) are the proximal ROS formed by the mitochondria, and the latter molecule is used as a secondary messenger to coordinate oxidative metabolism with changes in cell physiology. Like any other secondary messenger, H2O2 levels need to be regulated through its production and degradation and the mitochondria are enriched with the antioxidant defenses required to degrade ROS formed by nutrient oxidation and respiration. Recent work has also demonstrated that these antioxidant systems also carry the capacity to clear H2O2 formed outside of mitochondria. These observations led to the development of the postulate that the mitochondria serve as “ROS stabilizing devices” that buffer cellular H2O2 levels. Here, I provide an updated view on mitochondrial ROS homeostasis and discuss the “ROS stabilizing” function of the mitochondria in mammalian cells. This will be followed by a hypothetical discussion on the potential function of the mitochondria and proton motive force in degrading cellular H2O2 signals emanating from cytosolic enzymes.
The brain is a vulnerable metabolic organ and must adapt to different fuel conditions to sustain function. Nerve terminals are a locus of this vulnerability, but how they regulate ATP synthesis as ...fuel conditions vary is unknown. We show that synapses can switch from glycolytic to oxidative metabolism, but to do so, they rely on activity-driven presynaptic mitochondrial Ca2+ uptake to accelerate ATP production. We demonstrate that, whereas mitochondrial Ca2+ uptake requires elevated extramitochondrial Ca2+ in non-neuronal cells, axonal mitochondria readily take up Ca2+ in response to small changes in external Ca2+. We identified the brain-specific protein MICU3 as a critical driver of this tuning of Ca2+ sensitivity. Ablation of MICU3 renders axonal mitochondria similar to non-neuronal mitochondria, prevents acceleration of local ATP synthesis, and impairs presynaptic function under oxidative conditions. Thus, presynaptic mitochondria rely on MICU3 to facilitate mitochondrial Ca2+ uptake during activity and achieve metabolic flexibility.
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•Synapses rely on activity-driven mitochondrial ATP synthesis under oxidative conditions•Mitochondrial Ca2+ uptake is required to stimulate ATP synthesis in axons•The mitochondria Ca2+ uptake threshold is lower in axons than in non-neuronal cells•MICU3 controls the Ca2+ sensitivity of MCU in axonal mitochondria
Nerve terminals in the brain must synthesize ATP on demand to sustain function. Here, Ashrafi, de Juan-Sanz, et al. show that axonal mitochondria use the brain-specific MCU regulator MICU3 to allow efficient Ca2+ uptake in order to accelerate ATP production.
The brain is highly sensitive to proper fuel availability as evidenced by the rapid decline in neuronal function during ischemic attacks and acute severe hypoglycemia. We previously showed that ...sustained presynaptic function requires activity-driven glycolysis. Here, we provide strong evidence that during action potential (AP) firing, nerve terminals rely on the glucose transporter GLUT4 as a glycolytic regulatory system to meet the activity-driven increase in energy demands. Activity at synapses triggers insertion of GLUT4 into the axonal plasma membrane driven by activation of the metabolic sensor AMP kinase. Furthermore, we show that genetic ablation of GLUT4 leads to an arrest of synaptic vesicle recycling during sustained AP firing, similar to what is observed during acute glucose deprivation. The reliance on this biochemical regulatory system for “exercising” synapses is reminiscent of that occurring in exercising muscle to sustain cellular function and identifies nerve terminals as critical sites of proper metabolic control.
•The glucose transporter GLUT4 is present at nerve terminals•Neuronal activity recruits GLUT4 to presynaptic plasma membrane•GLUT4 is required for synaptic function during sustained activity•AMP kinase drives GLUT4 mobilization during activity
Ashrafi et al. identify the glucose transporter GLUT4 as a metabolic modulatory system that upregulates glycolysis in firing neurons to meet activity-driven ATP demand at nerve terminals. This GLUT4 regulatory module is essential for sustained synaptic transmission.
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