The reduced sleep duration previously observed in Camk2b knockout mice revealed a role for Ca2+/calmodulin-dependent protein kinase II (CaMKII)β as a sleep-promoting kinase. However, the underlying mechanism by which CaMKIIβ supports sleep regulation is largely unknown. Here, we demonstrate that activation or inhibition of CaMKIIβ can increase or decrease sleep duration in mice by almost 2-fold, supporting the role of CaMKIIβ as a core sleep regulator in mammals. Importantly, we show that this sleep regulation depends on the kinase activity of CaMKIIβ. A CaMKIIβ mutant mimicking the constitutive-active (auto)phosphorylation state promotes the transition from awake state to sleep state, while mutants mimicking subsequent multisite (auto)phosphorylation states suppress the transition from sleep state to awake state. These results suggest that the phosphorylation states of CaMKIIβ differently control sleep induction and maintenance processes, leading us to propose a “phosphorylation hypothesis of sleep” for the molecular control of sleep in mammals.
Surface water samples were collected at 15 sampling sites in the southeastern Japan Sea along the Japanese Archipelago for analysis of polycyclic aromatic hydrocarbons (PAHs). Water samples were fractionated by filtration through a glass fiber membrane (pore size 0.5 µm) and analyzed by high-performance liquid chromatography with fluorescence detection. Thirteen PAHs having 3 to 6 rings were found in the dissolved phase (DP) and 12 were found in the particulate phase (PP). The total (DP PP) PAH concentration ranged from 6.83 to 13.81 ng/L with the mean standard deviation (S.D.) concentration of 9.36 1.92 ng/L. The mean S.D. PAH concentration in the DP and PP was 5.99 1.80 and 3.38 0.65 ng/L, respectively. Three-ring PAHs predominated in the DP, while the proportion of 4-ring PAHs was higher in the PP. The mean total PAH concentration in the southeastern Japan Sea was higher than the concentration in the northwestern Japan Sea (8.5 ng/L). The Tsushima Current, which originates from the East China Sea with higher PAH concentration, is considered to be responsible for this higher concentration.
and mixing. While the 134 Cs and 137 Cs concentrations of highly contaminated surface seawater samples around the FDNPP have been studied extensively (Tsumune et al., 2012; Honda et al., 2012), relatively little information is available on radionuclide concentrations in seawater for other sea areas around the Japanese Archipelago. We previously reported low levels of 134 Cs and 137 Cs concentrations in surface water samples from the Pacific Ocean side of northeastern Japan, the Japan Sea, and the southwestern Okhotsk Sea before and after the FDNPP accident; however, the scope of these studies was somewhat cursory (Inoue et al., 2012a, b). Nonetheless, these studies illustrated the need for more extensive temporal and spatial investigations to assess the oceanic behaviors and fate of Fukushima-derived radionuclides around the Japanese Islands. We therefore used low-background γ-spectrometry to characterize the lateral variations of 134 Cs and 137 Cs concentrations in surface waters around the Japanese Archipelago in June and October 2011. These data were combined with 134 Cs deposition data (Ministry of Education,
Several studies have demonstrated increased pericardial effusion during anti-PD-1 immunotherapy, and treatment in patients who have developed pericardial tamponade is controversial. In this study, we describe a 63-year-old woman with stage IVA lung adenocarcinoma given pembrolizumab as a first-line therapy. After four cycles of pembrolizumab treatment, the patient suddenly developed a pericardial tamponade. Although pericardial effusion was increased, her tumor lesions were reduced. After an emergency pericardiocentesis, she continued the pembrolizumab therapy without recurrent pericardial effusions for three months until the primary tumor and lymph node metastasis progressed. Nine months after the pericardiocentesis, the patient died of progressive lung cancer, but pericardial effusion did not recur throughout the treatment course. This case study suggests that pembrolizumab therapy can be continued with a strict follow-up in some patients with pembrolizumab-induced pericardial tamponade.
Key points• Significant findings of the study Our patient developed pericardial tamponade during pembrolizumab treatment but continued pembrolizumab treatment after emergency pericardiocentesis without recurrent pericardial effusions.• What this study adds Pembrolizumab treatments may be resumed with a strict follow-up in some patients with treatment-related pericardial tamponade. Figure 1 (a) A computed tomography (CT) scan of the chest showed a mass lesion in the right upper lobe. A right supraclavicular lymph node metastasis infiltrated into the right thyroid lobe before pembrolizumab treatment. Mild pericardial effusion was observed. (b) After three cycles of pembrolizumab therapy, CT scan showed a positive response in the primary lesion and lymph node metastasis. (c) A CT revealed a sudden increase in pericardial effusion and the tumor lesions were reduced after four cycles of pembrolizumab therapy.
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