We report a precision measurement of the parity-violating asymmetry A_{PV} in the elastic scattering of longitudinally polarized electrons from ^{208}Pb. We measure A_{PV}=550±16(stat)±8(syst) parts ...per billion, leading to an extraction of the neutral weak form factor F_{W}(Q^{2}=0.00616 GeV^{2})=0.368±0.013. Combined with our previous measurement, the extracted neutron skin thickness is R_{n}-R_{p}=0.283±0.071 fm. The result also yields the first significant direct measurement of the interior weak density of ^{208}Pb: ρ_{W}^{0}=-0.0796±0.0036(exp)±0.0013(theo) fm^{-3} leading to the interior baryon density ρ_{b}^{0}=0.1480±0.0036(exp)±0.0013(theo) fm^{-3}. The measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.
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We report a precision measurement of the parity-violating asymmetry APV in the elastic scattering of longitudinally polarized electrons from 208Pb. We measure APV= 550 ± 16 (stat) ±8 (syst) parts per ...billion, leading to an extraction of the neutral weak form factor FW(Q2= 0.00616 GeV2) = 0.368 ± 0.013. Combined with our previous measurement, the extracted neutron skin thickness is Rn-Rp= 0.283 ± 0.071 fm. The result also yields the first significant direct measurement of the interior weak density of 208Pb: ρ$^0_W$ = -0.0796 ± 0.0036(exp) ± 0.0013(theo) fm-3 leading to the interior baryon density ρ$^0_b$ = 0.1480 ± 0.0036(exp) ± 0.0013(theo) fm-3. Finally, the measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.
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We have measured the beam-normal single-spin asymmetry $A_n$ in the elastic scattering of 1-3 GeV transversely polarized electrons from $^1$H and for the first time from $^4$He, $^{12}$C, and ...$^{208}$Pb. For $^1$H, $^4$He and $^{12}$C, the measurements are in agreement with calculations that relate $A_n$ to the imaginary part of the two-photon exchange amplitude including inelastic intermediate states. Surprisingly, the $^{208}$Pb result is significantly smaller than the corresponding prediction using the same formalism. These results suggest that a systematic set of new $A_n$ measurements might emerge as a new and sensitive probe of the structure of heavy nuclei.
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We report precision determinations of the beam-normal single spin asymmetries (A_{n}) in the elastic scattering of 0.95 and 2.18 GeV electrons off ^{12}C, ^{40}Ca, ^{48}Ca, and ^{208}Pb at very ...forward angles where the most detailed theoretical calculations have been performed. The first measurements of A_{n} for ^{40}Ca and ^{48}Ca are found to be similar to that of ^{12}C, consistent with expectations and thus demonstrating the validity of theoretical calculations for nuclei with Z≤20. We also report A_{n} for ^{208}Pb at two new momentum transfers (Q^{2}) extending the previous measurement. Our new data confirm the surprising result previously reported, with all three data points showing significant disagreement with the results from the Z≤20 nuclei. These data confirm our basic understanding of the underlying dynamics that govern A_{n} for nuclei containing ≲50 nucleons, but point to the need for further investigation to understand the unusual A_{n} behavior discovered for scattering off ^{208}Pb.
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Schizophrenia is associated with a broad range of severe and currently pharmacoresistant cognitive deficits. Prior evidence suggests that hypofunction of AMPA-type glutamate receptors (AMPARs) ...containing the subunit GLUA1, encoded by GRIA1, might be causally related to impairments of selective attention and memory in this disorder, at least in some patients. In order to clarify the roles of GluA1 in distinct cell populations, we investigated behavioural consequences of selective Gria1-knockout in excitatory neurons of subdivisions of the prefrontal cortex and the hippocampus, assessing sustained attention, impulsivity, cognitive flexibility, anxiety, sociability, hyperactivity, and various forms of short-term memory in mice. We found that virally induced reduction of GluA1 across multiple hippocampal subfields impaired spatial working memory. Transgene-mediated ablation of GluA1 from excitatory cells of CA2 impaired short-term memory for conspecifics and objects. Gria1 knockout in CA3 pyramidal cells caused mild impairments of object-related and spatial short-term memory, but appeared to partially increase social interaction and sustained attention and to reduce motor impulsivity. Our data suggest that reduced hippocampal GluA1 expression-as seen in some patients with schizophrenia-may be a central cause particularly for several short-term memory deficits. However, as impulse control and sustained attention actually appeared to improve with GluA1 ablation in CA3, strategies of enhancement of AMPAR signalling likely require a fine balance to be therapeutically effective across the broad symptom spectrum of schizophrenia.
Inflammaging represents an accepted concept where the immune system shifts to a low-grade chronic pro-inflammatory state without overt infection upon aging. In the CNS, inflammaging is mainly driven ...by glia cells and associated with neurodegenerative processes. White matter degeneration (WMD), a well-known process in the aging brain, manifests in myelin loss finally resulting in motor, sensory and cognitive impairments. Oligodendrocytes (OL) are responsible for homeostasis and maintenance of the myelin sheaths, which is a complex and highly energy demanding process sensitizing these cells to metabolic, oxidative and other forms of stress. Yet, the immediate impact of chronic inflammatory stress like inflammaging on OL homeostasis, myelin maintenance and WMD remains open.
To functionally analyze the role of IKK/NF-κB signaling in the regulation of myelin homeostasis and maintenance in the adult CNS, we established a conditional mouse model allowing NF-κB activation in mature myelinating oligodendrocytes. IKK2-CA
mice were characterized by biochemical, immunohistochemical, ultrastructural and behavioral analyses. Transcriptome data from isolated, primary OLs and microglia cells were explored by in silico pathway analysis and validated by complementary molecular approaches.
Chronic NF-κB activation in mature OLs leads to aggravated neuroinflammatory conditions phenocopying brain inflammaging. As a consequence, IKK2-CA
mice showed specific neurological deficits and impaired motoric learning. Upon aging, persistent NF-κB signaling promotes WMD in these mice as ultrastructural analysis revealed myelination deficits in the corpus callosum accompanied by impaired myelin protein expression. RNA-Seq analysis of primary oligodendrocytes and microglia cells uncovers gene expression signatures associated with activated stress responses and increased post mitotic cellular senescence (PoMiCS) which was confirmed by elevated senescence-associated β-galactosidase activity and SASP gene expression profile. We identified an elevated integrated stress response (ISR) characterized by phosphorylation of eIF2α as a relevant molecular mechanism which is able to affect translation of myelin proteins.
Our findings demonstrate an essential role of IKK/NF-κB signaling in mature, post-mitotic OLs in regulating stress-induced senescence in these cells. Moreover, our study identifies PoMICS as an important driving force of age-dependent WMD as well as of traumatic brain injury induced myelin defects.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Background Severe asthma is often poorly controlled and its prevalence in Spanish children is unknown. The aim was to determine the prevalence of difficult-to-control severe asthma in ...children, the agreement of asthma control between physicians and Spanish Guidelines for Asthma Management (GEMA), and the health-related quality of life (HRQoL) for children and parents. Methods Observational, cross-sectional, two-phase, multicentre study. In the first phase, all children who attended pneumology and allergy units during a three-month period were classified according to physicians’ criteria as patients with: asthma, severe asthma, or difficult-to-control severe asthma. Patients aged 6–14 years with severe asthma (difficult-to-control or controlled) were included in the second phase. Results 12,376 asthmatic children were screened in the first phase. According to physicians’ criteria, 8.8% (95% CI 8.3–9.3%) had severe asthma. Of these, 24.2% (95% CI, 21.7–26.8%) had difficult-to-control severe asthma. 207 patients with severe asthma (mean age 10.8 ± 2.3 years; 61.4% male; mean of 5.5 ± 3.4 years since asthma diagnosis) were included in the second phase. Compared to the patients with controlled asthma, children with difficult-to-control asthma had a higher number of exacerbations, emergency room or unscheduled primary care visits in the previous year ( p < 0.0001, all) and poor HRQoL ( p < 0.0001, both children and caregivers). 33.3% of patients with controlled asthma according to physicians’ criteria were poorly controlled according to GEMA. Conclusions Around one in four asthmatic children with severe disease had difficult-to-control asthma, although one third was underestimated by physicians. Children with difficult-to-control severe asthma had a poor HRQoL that also affected their parents.
Abstract
The anterior cingulate cortex (ACC) has been implicated in attention deficit hyperactivity disorder (ADHD). More specifically, an appropriate balance of excitatory and inhibitory activity in ...the ACC may be critical for the control of impulsivity, hyperactivity, and sustained attention which are centrally affected in ADHD. Hence, pharmacological augmentation of parvalbumin- (PV) or somatostatin-positive (Sst) inhibitory ACC interneurons could be a potential treatment strategy. We, therefore, tested whether stimulation of G
q
-protein-coupled receptors (G
q
PCRs) in these interneurons could improve attention or impulsivity assessed with the 5-choice-serial reaction-time task in male mice. When challenging impulse control behaviourally or pharmacologically, activation of the chemogenetic G
q
PCR hM3Dq in ACC PV-cells caused a selective decrease of active erroneous—i.e. incorrect and premature—responses, indicating improved attentional and impulse control. When challenging attention, in contrast, omissions were increased, albeit without extension of reward latencies or decreases of attentional accuracy. These effects largely resembled those of the ADHD medication atomoxetine. Additionally, they were mostly independent of each other within individual animals. G
q
PCR activation in ACC PV-cells also reduced hyperactivity. In contrast, if hM3Dq was activated in Sst-interneurons, no improvement of impulse control was observed, and a reduction of incorrect responses was only induced at high agonist levels and accompanied by reduced motivational drive. These results suggest that the activation of G
q
PCRs expressed specifically in PV-cells of the ACC may be a viable strategy to improve certain aspects of sustained attention, impulsivity and hyperactivity in ADHD.
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