New design method of FIR filters with SP2 coefficients based on a new linear programming relaxation with triangle inequalities

Publication in the conference proceedings of EUSIPCO, Toulouse, France, 200

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

Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making

「何を買うんだっけ」と「どれにしよう」を処理する2つの脳回路を明らかに --霊長類の生体脳で神経経路を可視化・操作する技術で解明、高次脳機能の理解へ大きく前進--. 京都大学プレスリリース. 2021-06-24.The primate prefrontal cortex (PFC) is situated at the core of higher brain functions via neural circuits such as those linking the caudate nucleus and mediodorsal thalamus. However, the distinctive roles of these prefronto-subcortical pathways remain elusive. Combining in vivo neuronal projection mapping with chemogenetic synaptic silencing, we reversibly dissected key pathways from dorsolateral part of the PFC (dlPFC) to the dorsal caudate (dCD) and lateral mediodorsal thalamus (MDl) individually in single monkeys. We found that silencing the bilateral dlPFC-MDl projections, but not the dlPFC-dCD projections, impaired performance in a spatial working memory task. Conversely, silencing the unilateral dlPFC-dCD projection, but not the unilateral dlPFC-MDl projection, altered preference in a decision-making task. These results revealed dissociable roles of the prefronto-subcortical pathways in working memory and decision-making, representing the technical advantage of imaging-guided pathway-selective chemogenetic manipulation for dissecting neural circuits underlying cognitive functions in primates

A Case of Endoscopic Mucosal Resection of Carcinoma in Adenoma at the Minor Duodenal Papilla

Here, we describe a case of minor papillary adenocarcinoma in adenoma that was treated with endoscopic mucosal resection (EMR). In a 67-year-old woman, sigmoid colon cancer was incidentally detected on preoperative upper gastrointestinal endoscopy. Endoscopy revealed a slightly elevated lesion at the minor duodenal papilla. The findings of a histopathologic examination were suggestive of adenocarcinoma. Computed tomography and magnetic resonance images identified a minute tumor, whereas endoscopic ultrasonography revealed that the tumor did not spread to the pancreas. We performed EMR of this lesion. There were no complications, and relapse has not occurred in 3 years. Cases of minor papillary adenocarcinoma treated with EMR are quite rare

Chemogenetic attenuation of cortical seizures in nonhuman primates

「てんかん」の発生を時間的・空間的にピンポイントで抑える画期的な治療法を開発 --世界で初めてサルでの有効性を実証、臨床応用に向け大きく前進--. 京都大学プレスリリース. 2023-03-01.Epilepsy is a disorder in which abnormal neuronal hyperexcitation causes several types of seizures. Because pharmacological and surgical treatments occasionally interfere with normal brain function, a more focused and on-demand approach is desirable. Here we examined the efficacy of a chemogenetic tool—designer receptors exclusively activated by designer drugs (DREADDs)—for treating focal seizure in a nonhuman primate model. Acute infusion of the GABAA receptor antagonist bicuculline into the forelimb region of unilateral primary motor cortex caused paroxysmal discharges with twitching and stiffening of the contralateral arm, followed by recurrent cortical discharges with hemi- and whole-body clonic seizures in two male macaque monkeys. Expression of an inhibitory DREADD (hM4Di) throughout the seizure focus, and subsequent on-demand administration of a DREADD-selective agonist, rapidly suppressed the wide-spread seizures. These results demonstrate the efficacy of DREADDs for attenuating cortical seizure in a nonhuman primate model

An Autopsy Case of Multiple Jejunal Diverticula Showing Severe Malabsorption

A rare autopsy case of multiple jejunal diverticula showing severe malabsorption is reported. A 56-year-old man was admitted due to vomiting and leg edema. On admission, his height was 160cm, his body weight was 39kg, and laboratory data revealed severe hypoproteinemia (TP: 4.0g/dl, ALB: 2.1g/dl). On the 14th day of admission, agonal breathing and disturbance of consciousness occurred after massive vomiting of gastric juice, and the patient died of respiratory failure. At autopsy, on abdominal sectioning, multiple diverticula situated on the mesenterium side of the enteron extending 70cm in length from the proximal jejunum were identified. However there were no findings suggesting perforation or diverticulitis. Histologically, the diverticula were lined by ordinal jejunum mucosa associated with muscularis mucosa, but the muscularis propria was not involved in the diverticular walls. The diverticula were identified as false diverticula. In both lower lungs, aspiration pneumonia was widely seen. The cause of death was considered to be aspiration pneumonia due to the vomiting caused by multiple jejunal diverticula.Only 16 case reports of multiple jejunal diverticulosis in Japan could be found in the literature however most of the reported complications were perforation and diverticulitis, and there were no reports of malabsorption. Therefore, the present case is significant concerning the cause of malabsorption in routine explorations

Personalized prediction of overall survival in patients with AML in non‐complete remission undergoing allo‐HCT

Allogenic hematopoietic stem cell transplantation (allo-HCT) is the standard treatment for acute myeloid leukemia (AML) in non-complete remission (non-CR); however, the prognosis is inconsistent. This study aimed to develop and validate nomograms and a web application to predict the overall survival (OS) of patients with non-CR AML undergoing allo-HCT (cord blood transplantation [CBT], bone marrow transplantation [BMT], and peripheral blood stem cell transplantation [PBSCT]). Data from 3052 patients were analyzed to construct and validate the prognostic models. The common significant prognostic factors among patients undergoing allo-HCT were age, performance status, percentage of peripheral blasts, cytogenetic risk, chemotherapy response, and number of transplantations. The conditioning regimen was a significant prognostic factor only in patients undergoing CBT. Compared with cyclophosphamide/total body irradiation, a conditioning regimen of ≥3 drugs, including fludarabine, with CBT exhibited the lowest hazard ratio for mortality (0.384; 95% CI, 0.266-0.554; p < 0.0001). A conditioning regimen of ≥3 drugs with CBT also showed the best leukemia-free survival among all conditioning regimens. Based on the results of the multivariable analysis, we developed prognostic models showing adequate calibration and discrimination (the c-indices for CBT, BMT, and PBSCT were 0.648, 0.600, and 0.658, respectively). Our prognostic models can help in assessing individual risks and designing future clinical studies. Furthermore, our study indicates the effectiveness of multi-drug conditioning regimens in patients undergoing CBT

Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling

Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson’s disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA–deficient Drosophila exhibits defects in neurotransmission during early developmental stages and progressive cell loss throughout the brain, including degeneration of the DA neurons. Lipid analysis of brain tissues reveals that the acyl-chain length of phospholipids is shortened by iPLA2-VIA loss, which causes endoplasmic reticulum (ER) stress through membrane lipid disequilibrium. The introduction of wild-type human iPLA2-VIA or the mitochondria–ER contact site-resident protein C19orf12 in iPLA2-VIA–deficient flies rescues the phenotypes associated with altered lipid composition, ER stress, and DA neurodegeneration, whereas the introduction of a disease-associated missense mutant, iPLA2-VIA A80T, fails to suppress these phenotypes. The acceleration of α-Syn aggregation by iPLA2-VIA loss is suppressed by the administration of linoleic acid, correcting the brain lipid composition. Our findings suggest that membrane remodeling by iPLA2-VIA is required for the survival of DA neurons and α-Syn stability

A Case of Unusual Polypoid Mixed Hemangioma of the Sigmoid Colon: Possibly an Angioadenomatous Polyp

Herein, we report on an unusual case of polypoid mixed hemangioma of the sigmoid colon. An 85-year-old woman who underwent colonoscopic examination was found to have a smooth, red polypoid tumor, 6mm in diameter, in the sigmoid colon. The polyp was resected endoscopically. Microscopically, the polyp contained two pathologic components: (i) adenomatous proliferative glands as the epithelial component; and (ii) mixed hemangioma as the mesenchymal component. On the basis of these findings, a pathological diagnosis of angioadenomatous polyp was made. Although seven previous cases of polypoid hemangioma located in the submucosa have been reported in the literature, the present case is the first in which the hemangioma is localized only in the mucosa. The mixed hemangioma may be the pathogen stimulating the adenomatous proliferation of the glands