During brain development, once primary neural networks are formed, they are largely sculpted by environmental stimuli. The juvenile brain has a unique time window termed the critical period, in which ...neuronal circuits are remodeled by experience. Accumulating evidence indicates that abnormal rewiring of circuits in early life contributes to various neurodevelopmental disorders at later stages of life. Recent studies implicate two important aspects for activation of the critical period, both of which are experience‐dependent: (a) proper excitatory/inhibitory (E/I) balance of neural circuit achieved during developmental trajectory of inhibitory interneurons, and (b) epigenetic regulation allowing flexible gene expression for neuronal plasticity. In this review, we discuss the molecular mechanisms of juvenile brain plasticity from the viewpoints of transcriptional and chromatin regulation, with a focus on Otx2 homeoprotein. Depending on experience, Otx2 is transported into cortical parvalbumin‐positive interneurons (PV cells), where it induces PV cell maturation to activate the critical period. Understanding the unique behavior and function of Otx2 as a “messenger” of experience should therefore provide insights into mechanisms of juvenile brain development. Recently identified downstream targets of Otx2 suggest novel roles of Otx2 in homeostasis of PV cells, and, moreover, in regulation of chromatin state, which is important for neuronal plasticity. We further discuss epigenetic changes during postnatal brain development spanning the critical period. Different aspects of chromatin regulation may underlie experience‐dependent neuronal development and plasticity.
Juvenile brain has a unique time window called critical period, in which neuronal circuits are remodeled by experience. Here, we overview the maturation of the key player, GABAergic interneuron, and focus on Otx2 as a messenger of experience. Further, juvenile plasticity in light of epigenetic and chromatin regulation is discussed.
We analyzed 18F-Fludeoxyglucose positron emission tomography (FDG-PET) and 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) performed for ...cardiac sarcoidosis (CS) patients taking prednisolone, identified recurrence by FDG-PET, and investigated BMIPP as a recurrence and prognostic factor in CS.
CS patients who underwent BMIPP and FDG-PET within 2 months were enrolled. The recurrence-free group included patients with standardized uptake value (SUVmax) < 4 in the myocardium consecutively for ≥ 2 years. The total BMIPP SPECT defect score (BDS) was used to estimate myocardial damage. The predictability of the initial BDS and SUVmax for major adverse cardiac events (MACE) was analyzed using Kaplan–Meier analysis. Overall, 73 patients and 250 BMIPP and FDG-PET sets were analyzed retrospectively (mean follow-up, 3.5 years). The BDS was significantly greater for the recurrence group (N = 21) vs recurrence-free group (20 ± 13 vs 14 ± 12, P = 0.041). Patients with BDS ≥16 had a significantly higher MACE rate than patients with BDS < 16 (log-rank test, P = 0.016). However, MACE occurrence was comparable between patients with SUVmax ≥ 4 and < 4.
BDS is a predictive marker of recurrence and MACE. SUV is not related to MACE. Recurrence, defined by prednisolone treatment-induced SUV variability, was observed in approximately 30% of CS patients.
Objective
To clarify the link between cardiac sarcoidosis (CS) and extra-CS (ECS) in systemic CS (SCS) patients in terms of extent and clinical outcome by serial FDG-PET/CT.
Methods
Thirty-five SCS ...patients treated for > 2 years were enrolled in this study. In the overall analysis, patient-based comparisons of the complete resolution (CR) and recurrence rate between CS and ECS lesions were performed. Then, subgroup analyses were performed according to the extent (mono- vs. multi-organ ECS group) and clinical outcome (stable vs. unstable ECS group) of ECS. Pre-treatment cardiac FDG uptake was compared between the mono- and multi-organ ECS groups. The rates of CR, recurrence, and major adverse cardiac events (MACE) were compared between the two groups.
Results
The CR rate was significantly higher in CS than ECS lesions 77.1% (27/35) vs. 48.5% (17/35), p = 0.01, whereas recurrence rates were similar between CS and ECS 40.7% (11/27) vs. 58.8% (10/17). Both the mono- and multi-organ ECS groups showed similar SUV
max
, cardiac metabolic volume, and cardiac metabolic activity in the pre-treatment condition. The CR rates were similar between the mono- and multi-organ ECS groups 71.4% (15/21) vs. 85.7% (12/14), but the recurrence rate was significantly lower in the multi-organ ECS group 60.0% (9/15) vs. 16.7% (2/12), p = 0.02. The CR 71.4% (5/7) vs. 78.6% (22/28) and recurrence rates 60.0% (3/5) vs. 36.3% (8/22) were not significantly different between the stable and unstable ECS groups. The occurrence of MACE was also not significantly different between the mono- and multi-organ ECS groups 19.0% (4/21) vs. 28.6% (4/14) or between the stable and unstable ECS groups 42.9% (3/7) vs. 17.8% (5/28).
Conclusions
CS lesions respond to treatment better than ECS lesions, and the extent and clinical outcome of ECS lesion are not linked with those of CS lesions.
The antibody titer is known to wane within months after receiving two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine. However, knowledge of the cellular immune response dynamics ...following vaccination is limited. This study to aimed to determine antibody and cellular immune responses following vaccination, and the incidence and determinants of breakthrough infection.
This prospective cohort study a 6-month follow-up period was conducted among Japanese healthcare workers. All participants received two doses of BNT162b2 vaccine. Anti-SARS-CoV-2 antibody titers and T-cell immune responses were measured in serum samples collected at several timepoints before and after vaccination.
A total of 608 participants were included in the analysis. Antibody titers were elevated 3 weeks after vaccination and waned over the remainder of the study period. T-cell immune responses showed similar dynamics. Six participants without predisposing medical conditions seroconverted from negative to positive on the IgG assay for nucleocapsid proteins, indicating breakthrough SARS-CoV-2 infection. Five of the six breakthrough infections were asymptomatic.
Both humoral and cellular immunity waned within 6 months after BNT162b2 vaccination. The incidence of asymptomatic breakthrough infection within 6 months after vaccination was approximately one percent.
UMIN000043340.
Glutamate acts as the main excitatory neurotransmitter in the brain and plays a vital role in physiological and pathological neuronal functions. In mammals, glutamate can cause detrimental ...excitotoxic effects under anoxic conditions. In contrast,
Trachemys scripta
, a freshwater turtle, is one of the most anoxia-tolerant animals, being able to survive up to months without oxygen. Therefore, turtles have been investigated to assess the molecular mechanisms of neuroprotective strategies used by them in anoxic conditions, such as maintaining low levels of glutamate, increasing adenosine and GABA, upregulating heat shock proteins, and downregulating K
ATP
channels. These mechanisms of anoxia tolerance of the turtle brain may be applied to finding therapeutics for human glutamatergic neurological disorders such as brain injury or cerebral stroke due to ischemia. Despite the importance of glutamate as a neurotransmitter and of the turtle as an ideal research model, the glutamatergic circuits in the turtle brain remain less described whereas they have been well studied in mammalian and avian brains. In reptiles, particularly in the turtle brain, glutamatergic neurons have been identified by examining the expression of vesicular glutamate transporters (VGLUTs). In certain areas of the brain, some ionotropic glutamate receptors (GluRs) have been immunohistochemically studied, implying that there are glutamatergic target areas. Based on the expression patterns of these glutamate-related molecules and fiber connection data of the turtle brain that is available in the literature, many candidate glutamatergic circuits could be clarified, such as the olfactory circuit, hippocampal–septal pathway, corticostriatal pathway, visual pathway, auditory pathway, and granule cell–Purkinje cell pathway. This review summarizes the probable glutamatergic pathways and the distribution of glutamatergic neurons in the pallium of the turtle brain and compares them with those of avian and mammalian brains. The integrated knowledge of glutamatergic pathways serves as the fundamental basis for further functional studies in the turtle brain, which would provide insights on physiological and pathological mechanisms of glutamate regulation as well as neural circuits in different species.
We conducted a mass-balance study of debris-free Trambau Glacier in the Rolwaling region, Nepal Himalaya, which is accessible to 6000 m a.s.l., to better understand mass-balance processes and the ...effect of precipitation on these processes on high-elevation Himalayan glaciers. Continuous in situ meteorological and mass-balance observations that spanned the three melt seasons from May 2016 are reported. An energy- and mass-balance model is also applied to evaluate its performance and sensitivity to various climatic conditions. Glacier-wide mass balances ranging from −0.34 ± 0.38 m w.e. in 2016 to −0.82 ± 0.53 m w.e. in 2017/18 are obtained by combining the observations with model results for the areas above the highest stake. The estimated long-term glacier mass balance, which is reconstructed using the ERA-Interim data calibrated with in situ data, is −0.65 ± 0.39 m w.e. a−1 for the 1980–2018 period. A significant correlation with annual precipitation (r = 0.77, p < 0.001) is observed, whereas there is no discernible correlation with summer mean air temperature. The results indicate the continuous mass loss of Trambau Glacier over the last four decades, which contrasts with the neighbouring Mera Glacier in balance.
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