Novel Heterogenous CHS1 Mutations Identified in Five Japanese Patients with Chediak-Higashi Syndrome

Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder characterized by oculocutaneous albinism, recurrent bacterial infections and progressive neurological dysfunction. We demonstrate novel heterogenous mutations of CHS1, the responsive gene of CHS, identified in five Japanese patients with CHS. Patients 1, 2, and 3 were siblings, and they had albinism of the skin and hair. They all had a heterogenous two-base deletion (c.5541-5542 del AA, p.Q1847fsX1850) in exon 18. Patient 4 had a heterogenous single-base insertion (c.3944-3945 ins C, p.T1315fsX1331) in exon 10. The patient exhibited severe early-onset phenotype and suffered from hemophagocytic lymphohistiocytosis. Patient 5 had two heterogenous nonsense mutations; c.7982C>G, p.S2661X in exon 30 and c.8281A>T, p.R2761X in exon 31. The patient suffered from infections in childhood and had visual disturbance and albinism of the skin and hair. The CHS1 mutations described here have not been reported previously

Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector

霊長類においてウイルスベクターを用いた痛覚神経への遺伝子導入に成功 --神経障害性疼痛治療への応用に期待--. 京都大学プレスリリース. 2021-08-12.Adeno-associated virus 6 has been proposed as a potential vector candidate for specific gene expression in pain-related dorsal root ganglion neurons, but this has not been confirmed in nonhuman primates. The aim of our study was to analyze the transduction efficiency and target specificity of this viral vector in the common marmoset by comparing with those in the rat. When green fluorescent protein-expressing serotype-6 vector was injected into the sciatic nerve, the efficiency of gene expression in dorsal root ganglion neurons was comparable in both species. We found that the serotype-6 vector was largely specific to the pain-related ganglion neurons in the marmoset as well as in the rat, whereas the serotype-9 vector resulted in contrasting effects in the two species. Neither AAV6 nor AAV9 resulted in DRG toxicity when administered via the sciatic nerve, suggesting this as a safer route of sensory nerve transduction than the currently used intrathecal or intravenous administrative routes. Furthermore, the adeno-associated virus 6 vector could be an optimal serotype for gene therapy for human chronic pain that has minimal effect on other somatosensory functions of dorsal root ganglion neurons

Chemogenetic sensory fMRI reveals behaviorally relevant bidirectional changes in primate somatosensory network

手と足の感覚は、実は脳の中でつながっていた --脳障害による活動変化の広がりを見ることで常識を覆す発見、脳機能・疾患機序の理解へ前進--. 京都大学プレスリリース. 2021-10-21.Concurrent genetic neuromodulation and functional magnetic resonance imaging (fMRI) in primates has provided a valuable opportunity to assess the modified brain-wide operation in the resting state. However, its application to link the network operation with behavior still remains challenging. Here, we combined chemogenetic silencing of the primary somatosensory cortex (SI) with tactile fMRI and related behaviors in macaques. Focal chemogenetic silencing of functionally identified SI hand region impaired grasping behavior. The same silencing also attenuated hand stimulation-evoked fMRI signal at both the local silencing site and the anatomically and/or functionally connected downstream grasping network, suggesting altered network operation underlying the induced behavioral impairment. Furthermore, the hand region silencing unexpectedly disinhibited foot representation with accompanying behavioral hypersensitization. These results demonstrate that focal chemogenetic silencing with sensory fMRI in macaques unveils bidirectional network changes to generate multifaceted behavioral impairments, thereby opening a pivotal window toward elucidating the causal network operation underpinning higher brain functions in primates

Causal Role of Neural Signals Transmitted From the Frontal Eye Field to the Superior Colliculus in Saccade Generation

The frontal eye field (FEF) and superior colliculus (SC) are major and well-studied components of the oculomotor system. The FEF sends strong projections to the SC directly, and neurons in these brain regions transmit a variety of signals related to saccadic eye movements. Electrical microstimulation and pharmacological manipulation targeting the FEF or SC affect saccadic eye movements. These data suggest the causal contribution of each region to saccade generation. To understand how the brain generates behavior, however, it is critical not only to identify the structures and functions of individual regions, but also to elucidate how they interact with each other. In this review article, we first survey previous works that aimed at investigating whether and how the FEF and SC interact to regulate saccadic eye movements using electrophysiological and pharmacological techniques. These works have reported what signals FEF neurons transmit to the SC and what roles such signals play in regulating oculomotor behavior. We then highlight a recent attempt of our own that has applied an optogenetic approach to stimulate the neural pathway from the FEF to the SC in nonhuman primates. This study has shown that optogenetic stimulation of the FEF-SC pathway is sufficiently effective not only to modulate SC neuron activity, but also to evoke saccadic eye movements. Although the oculomotor system is a complex neural network composed of numbers of cortical and subcortical regions, the optogenetic approach will provide a powerful strategy for elucidating the role of each neural pathway constituting this network

国立国語研究所研究資料室における個人情報の取り扱いについて

国立国語研究所 研究情報発信センター 非常勤研究員国立国語研究所 研究系 言語変化研究領域Adjunct Researcher, Center for Research Resources, NINJALLanguage Change Division, Research Department, NINJAL学術情報・データのオープン化，共有化の流れを踏まえ，国立国語研究所は研究資料室に収蔵されている調査票や録音テープ等の原資料の外部公開へ向けて，検索手段や利用に関する規則等の整備を行った。その過程で収蔵する資料群の中に個人情報を含む研究資料が全体の3割程度存在することが判明した。これらの個人情報の保護と研究資料の利用をどのように両立させるかが研究資料室収蔵資料公開の大きな鍵となった。本稿では，『公文書等の管理に関する法律』や『独立行政法人等の保有する個人情報の保護に関する法律』等の関係する法規を検討しつつ，研究資料を利用・公開するための規程整備について述べる。The National Institute for Japanese Language and Linguistics (NINJAL) has improved and established rules to open research materials to the public, following the direction of open access of scholarly information and data. In the process, it turned out that research materials comprised personal information at the rate of 30 percent. The key to the case is how to achieve a good balance between personal information protection and utilization of research materials. This paper describes the preparation of regulations for utilization of research materials, referring to "Public Records and Archives Management Act" and "Act on the Protection of Personal Information Held by Incorporated Administrative Agencies, etc.