Pcdhβ deficiency affects hippocampal CA1 ensemble activity and contextual fear discrimination

Clustered protocadherins (Pcdhs), a large group of adhesion molecules, are important for axonal projections and dendritic spread, but little is known about how they influence neuronal activity. The Pcdhβ cluster is strongly expressed in the hippocampus, and in vivo Ca2+ imaging in Pcdhβ-deficient mice revealed altered activity of neuronal ensembles but not of individual cells in this region in freely moving animals. Specifically, Pcdhβ deficiency increased the number of large-size neuronal ensembles and the proportion of cells shared between ensembles. Furthermore, Pcdhβ-deficient mice exhibited reduced repetitive neuronal population activity during exploration of a novel context and were less able to discriminate contexts in a contextual fear conditioning paradigm. These results suggest that one function of Pcdhβs is to modulate neural ensemble activity in the hippocampus to promote context discrimination

Orchestrated ensemble activities constitute a hippocampal memory engram

The brain stores and recalls memories through a set of neurons, termed engram cells. However, it is unclear how these cells are organized to constitute a corresponding memory trace. We established a unique imaging system that combines Ca2+ imaging and engram identification to extract the characteristics of engram activity by visualizing and discriminating between engram and non-engram cells. Here, we show that engram cells detected in the hippocampus display higher repetitive activity than non-engram cells during novel context learning. The total activity pattern of the engram cells during learning is stable across post-learning memory processing. Within a single engram population, we detected several sub-ensembles composed of neurons collectively activated during learning. Some sub-ensembles preferentially reappear during post-learning sleep, and these replayed sub-ensembles are more likely to be reactivated during retrieval. These results indicate that sub-ensembles represent distinct pieces of information, which are then orchestrated to constitute an entire memory

Dimensional reduction by geometrical frustration in a cubic antiferromagnet composed of tetrahedral clusters

Dimensionality is a critical factor in determining the properties of solids and is an apparent built-in character of the crystal structure. However, it can be an emergent and tunable property in geometrically frustrated spin systems. Here, we study the spin dynamics of the tetrahedral cluster antiferromagnet, pharmacosiderite, via muon spin resonance and neutron scattering. We find that the spin correlation exhibits a two-dimensional characteristic despite the isotropic connectivity of tetrahedral clusters made of spin 5/2 Fe3+ ions in the three-dimensional cubic crystal, which we ascribe to two-dimensionalisation by geometrical frustration based on spin wave calculations. Moreover, we suggest that even one-dimensionalisation occurs in the decoupled layers, generating low-energy and one-dimensional excitation modes, causing large spin fluctuation in the classical spin system. Pharmacosiderite facilitates studying the emergence of low-dimensionality and manipulating anisotropic responses arising from the dimensionality using an external magnetic field

Attempt to Characterize Egyptian Painting Layers by GC/MS and Optical Method

Organic binding media and color materials used in Egyptian wall paintings were characterized using gas chromatograph-mass spectrometry (GC-MS). Fourier-transform infrared spectroscopy (FT-IR) and Raman spectroscopy. The small samples of the wall paintings were obtained from the debris in Funeral House (Egyptian House) in Tuna el-Gabal that was at the age of Persian or Ptolmaic Period. The aim of this study is to investigate a possibility of discrimination between Arabic gum and animal protein-based binders used in ancient Egypt and to recognize the use of mixtures of the two products. The GC-MS results showed that saturated fatty acid esters and the compound which seemed to be fatty acid glyceride were detected in the extract of the wall surface. Unsaturated aliphatic alcohols, esters, and the components with a steroid frame were observed from the direct probe method of EI-MS. In FT-IR, the absorption bands of calcium hydroxide in the red part of the painting and inorganic oxide in the black part were observed. In Raman spectra, it was supposed that amorphous carbon was used for color material of the black district and cinnabar (HgS) was for that of the red part. In addition, the color materials with fluorescence were detected in the red and blue part of surface

Characterization of Organic Binding Media Used in Egyptian Painting Layers by GC/MS

Organic binding media used in Egyptian wall paintings was characterized using gas chromatograph-mass spectrometry (GC-MS). Samples of the wall paintings were obtained from the dubris in the mastaba of Idout, Saqqara in Egypt. The aim of this study is to investigate the possibility of discrimination between arabic gum and animal protein-based binders used in ancient Egypt. In this present study, three methods of sample preparation and injection in GC-MS (double-shot injection, reaction pyrolysis and liquid-injection) were tested for the most sensitive detection of the organic binding media. The GC-MS results showed that the double-shot injection and liquid-injection methods detected no natural products, but the reaction pyrolysis method could detect saturated fatty-acid esters and fatty-acid glyceride-like compounds. However, these organic compounds found at the Idout wall painting are almost consistent with the previously reported compounds that were detected from the wall painting samples obtained from the Funeral House in Tuna el-Gabal. In conclusion, the organic binding media could not be discriminated again.ガスクロマトグラフィー質量分析（GC-MS）の3種類の測定手法、ダブルショット法、反応熱分解法および液体注入法を用いて、エジプト壁画に使用されている接着剤などの有機化合物の分析を行った。試料はサッカラのイドゥートの埋葬室から得られた壁画の小片である。ダブルショット法、液体注入法を用いたGC-MS測定では、天然物由来の有機化合物を検出することができなかった。反応熱分解法を用いて壁画表面をGC-MSで分析した結果、飽和脂肪酸エステル類が強く、他にも脂肪酸グリセリド様と思われる化合物を検出した。その結果は、前回測定したツナ・エル・ガバル遺跡の壁画小片から検出した有機物とほぼ同じ化合物群であり、今回も壁画に使用されている接着材の成分を識別することはできなかった。3種類の分析方法の中で反応熱分解法が、有機化合物に対してもっとも感度が高かった

Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4+ cTfh cells were significantly decreased and the percentage of IFN-γ+ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Sevoflurane-induced amnesia is associated with inhibition of hippocampal cell ensemble activity after learning

General anesthesia could induce amnesia, however the mechanism remains unclear. We hypothesized that suppression of neuronal ensemble activity in the hippocampus by anesthesia during the post-learning period causes retrograde amnesia. To test this hypothesis, two experiments were conducted with sevoflurane anesthesia (2.5%, 30 min): a hippocampus-dependent memory task, the context pre-exposure facilitation effect (CPFE) procedure to measure memory function and in vivo calcium imaging to observe neural activity in hippocampal CA1 during context exploration and sevoflurane/home cage session. Sevoflurane treatment just after context pre-exposure session impaired the CPFE memory, suggesting sevoflurane induced retrograde amnesia. Calcium imaging showed sevoflurane treatment prevented neuronal activity in CA1. Further analysis of neuronal activity with non-negative matrix factorization, which extracts neural ensemble activity based on synchronous activity, showed that sevoflurane treatment reduced the reactivation of neuronal ensembles between during context exploration just before and one day after sevoflurane inhalation. These results suggest that sevoflurane treatment immediately after learning induces amnesia, resulting from suppression of reactivation of neuronal ensembles