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Prefronto-thalamic hypoconnectivity in schizophrenia: Monkey to human translation of critical pathways for symptom-related functions
No full textAim: Recent advances in genetic neuromodulation technology have enabled circuit-specific interventions in nonhuman primates (NHPs), thereby revealing the causal functions of specific neural circuits. Using this technology, we recently identified in NHPs the causal roles of the dorsolateral prefrontal cortex (DLPFC) to the lateral part of the mediodorsal thalamic nucleus (MDl) pathway in working memory, a core deficit in schizophrenia (SCZ) patients. Here, we aimed to examine if this alteration was translational to the human patients with SCZ.Methods: Using the publicly available, multisite, multi-disorder magnetic resonance imaging (MRI) dataset, we evaluated the resting-state functional connectivity in this DLPFC-MDl pathway and examined whether the alteration was, if any, specific to SCZ (N = 91) and not to healthy controls (HCs, N = 511), patients with major depressive disorder (MDD, N = 133), and autism spectrum disorders (ASDs, N = 120).Results: We found that the DLPFC-MDl connectivity was significantly reduced in the SCZ group compared to HCs, whereas no such hypoconnectivity was observed in the ASD or MDD groups, suggesting a disease-dependent profile of altered connectivity at rest. This hypoconnectivity was not observed between the DLPFC and other neighboring thalamic nuclei, suggesting a focal thalamic anomaly underlying the altered connectivity in SCZ.Conclusion: These results support the potential of translating pathway-specific causal insights from NHP studies to identify disease-specific connectivity alterations in neuropsychiatric disorders with related symptoms in humans.Keywords: functional connectivity; pathway‐specific silencing; resting‐state functional MRI; schizophrenia; thalamus.journal articl
近赤外レーザーによる局所加温と量子ドットでの温度センシングによる脳温度検出機構の解明
No full text脳は、エネルギー代謝により多量の熱を産生するにもかかわらず、脳内温度は安定に保たれている。特に、神経活動が時空間的に多様な熱源となるため、脳には極めて精緻な温度調整機構が存在し、脳内に張り巡らされた血管網がこの役割を担っていると考えられている。しかし、脳内の微小領域において温度変化を感知し、それに応答して血流を制御するメカニズムは、未だ十分に解明されていない。局所的な温度調節機構を明らかにするには、細胞レベルでの温度操作と高精度な温度計測が不可欠である。本研究では、近赤外レーザーによる局所加温と量子ドットによる温度センシングを融合した実験システムを構築した。具体的には、二光子励起顕微鏡に独立した2つの光学スキャン系を組み込み、細胞イメージング、温度センシング、局所加温を同時に実施可能とした。これにより、各種脳細胞への局所加温が脳血流に与える影響を調べた。直径10 μmの円形領域に1040 nmレーザーを約0.5秒間照射した結果、中心から35 μm以内で平均約0.5℃（約1％）の温度上昇が認められた。一方、35 μmを超える範囲では温度上昇は検出されなかった。神経細胞（GCaMP）、アストロサイト（GFP）、ミクログリア（GFP）をそれぞれ標識し、単一細胞をターゲットとして局所加温を行った。その結果、神経細胞に対する局所加温では、周囲の細動脈および毛細血管において血管径の有意な変化が認められた。さらに、レーザー照射による温度上昇時に神経発火の有無にかかわらず、血管径の変化は生じていた。一方、アストロサイトやミクログリアに対する局所加温では、細動脈・毛細血管ともに有意な血管径変化は見られなかった。これらの結果は、単一神経細胞の温度変化が脳血流変化を誘導することを示し、さらに神経細胞と脳血管網が連動して局所的な熱負荷に応答する精緻な温度維持システムを備えていることを直接的に明らかにした。量子生命科学会第７回大会conference poste
Quantum Life Science: A New Paradigm for Life Science Research
No full textQuantum Life Science integrates quantum technology with life sciences, focusing on three key areas: nanoscale quantum biosensors, quantum technology-based hyperpolarized MRI/NMR, and quantum biology. Nanodiamonds with nitrogen-vacancy centers serve as innovative cellular sensors, while hyperpolarized MRI/NMR techniques enhance metabolic imaging sensitivity. Quantum effects in biological systems, such as photosynthesis, magnetoreception, and enzyme catalysis, inspire biomimetic technologies. This field advances drug discovery, medical diagnostics, and understanding complex biological phenomena. Future developments may include accessible hyperpolarization technologies and quantum-inspired nanotechnologies, potentially revolutionizing energy harvesting and medical imaging. This interdisciplinary approach bridges quantum physics, biology, and technology, opening new avenues for scientific exploration and practical applications in various fields.journal articl
Evaluating Soil Temperature Variations for Enhanced Radon Monitoring in Volcanic Regions
No full textSoil temperature, a key factor in subsurface geochemical processes, is influenced by environmental and geological dynamics. This study analyzed hourly soil temperature variations at depths of 10 to 100 cm near the Sakurajima volcano, alongside concurrent ambient temperature measurements. By applying temperature models and statistical methods, we characterized both seasonal and short-term thermal dynamics, including soil-atmosphere thermal coupling. Our findings revealed a depth-dependent thermal diffusivity, establishing distinct thermal regimes within the soil profile. The soil’s strong thermal buffering capacity, evidenced by increasing amplitude attenuation and temporal lag with depth, allowed us to identify optimal instrument placement depths (80–100 cm) for minimal diurnal temperature influence. We also quantified the relationship between ambient temperature fluctuations and soil thermal response at various depths, as well as the impact of these temperature variations on soil permeability. These results enhance our understanding of subsurface thermal behaviour in volcanic environments and offer practical guidance for environmental monitoring and geohazard studies.journal articl
重粒子線治療を受けたがん患者の闘病体験の中にあるレジリエンス
No full text本研究の目的は、重粒子線治療を受けたがん患者の闘病体験の中にあるレジリエンスを明らかにすることである。重粒子線治療を受けたがん患者4名を対象に、半構造化面接を実施し、質的記述的に分析した。その結果、重粒子線治療を受けたがん患者の闘病体験の中にあるレジリエンスとして【自分にとって価値ある治療に臨む力】、【不安を抱えながらも周囲と支え合い重粒子線治療に向かう力】、【重粒子線治療を前向きに捉え日常を取り戻す力】が抽出された。重粒子線治療を受けたがん患者のレジリエンスを支える看護介入として、１）重粒子線治療選択までの過程を踏まえた支援を行う、２）看護の専門性を発揮し患者のニーズに沿った情報を提供する、3）患者が抱える不安に配慮したセルフケア支援の必要性が示唆された。This study investigated the resilience of patients with cancer who had undergone heavy-ion therapy. Semi-structured interviews were conducted with four patients, and the results were analyzed using qualitative and descriptive methods. Three elements of resilience were indentified in patients with cancer who had undergone heavy ion therapy: (1) the ability to face treatment as valuable to themselves, (2) the ability to face heavy ion therapy while supporting themselves and others despite feelings of anxiety, and (3) the ability to adopt a positive outlook toward heavy ion therapy and resume daily life. The following nursing interventions were suggested to support the resilience of patients with cancer undergoing heavy ion therapy: 1) providing support based on the process leading to the selection of heavy ion therapy, 2) applying nursing expertise and providing information tailored to the patient's needs, and 3) offering self-care support that considers the patient's anxieties.journal articl
Spontaneous and Radiation-Induced Mammary and Thyroid Tumorigenesis in LEW and (SD×COP)F1 Brca1L63X/+ Rats
No full textBackground/Aim: Carriers of germline mutations in BRCA1/2 have an increased risk of carcinogenesis in breast, ovary, pancreas, stomach, etc. We previously established the Brca1 mutant (Brca1L63X/+) rat model on a Sprague-Dawley (SD) background, and it displayed an increased risk of mammary carcinoma during middle age after γ-ray exposure at 7 weeks of age. At younger ages, this model showed no increased risk of mammary tumors or other tumors, probably because of the relatively high susceptibility of the SD background to radiation-induced mammary carcinogenesis. Thus, we established new Brca1L63X/+ rat models on backgrounds with less susceptibility to mammary carcinogenesis and elucidated tumor risk in mammary tissue and other organs.Materials and Methods: Female Brca1L63X/+ rats and wild-type (WT) littermates on the LEW background or the F1 hybrid between Copenhagen and SD [(SD×COP)F1] were whole-body irradiated with γ rays at age 7 weeks or left non-irradiated. The rats were palpated weekly, and tumors reaching ~2 cm were biopsied and diagnosed. Rats that were identified as having mammary carcinoma or showing general deterioration were autopsied, and mammary tumors and other tissues, including thyroid, were analyzed for pathology.Results: The incidence of mammary carcinomas was similar between Brca1L63X/+ and WT rats on the LEW or (SD×COP)F1 background. Non-irradiated Brca1L63X/+ rats on the LEW background had significantly higher prevalence of thyroid tumors than non-irradiated WT rats. WT rats tended to have increased prevalence of thyroid carcinoma after radiation exposure, but the prevalence did not differ between irradiated Brca1L63X/+ and WT rats.Conclusion: Brca1L63X/+ rats on the LEW and (SD×COP)F1 backgrounds did not recapitulate the human breast carcinogenesis phenotype. Notably, our findings suggest that a germline mutation in Brca1 increases the prevalence of spontaneous thyroid tumors.journal articl
Evaluation of myocardial fibrosis and wall motion abnormality with 68Ga‑FAPI PET/MR in coronary heart disease
No full textBackground To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/MR in coronary heart disease (CHD) and its association with abnormal wall motion.Results In this prospective study, participants with CHD after PCI (Percutaneous Coronary Intervention) underwent gallium 68 (68 Ga)-labeled FAPI PET/MR imaging. FAP signal was quantified using standardized uptake values. CardiacMRI yielded functional parameters and area of injury (MRI non-viable). Abnormal wall motion identified by myocardial strain analysis was evaluated using integrated analysis of late gadolinium enhancement (LGE) and FAP signal. Thecorrelations between FAP signal and clinical parameters were explored. Forty-two participants were included and FAP signal was higher in left ventricle regional myocardium compared with remote normal areas (SUVmax, 5.0±1.8 vs1.2±0.4; p<.001). In total, 432 segments (432/714, 60.50%) displayed impaired wall motion. In integrated analysis, the highest wall motion abnormality score was observed in the FAPI active/MRI non-viable group (11.0±5.2). FAP signal was positively correlated with K time (SUVpeak: R=0.48; p=.046; SUVmean: R=0.57; p=.014) and negatively correlated with Angle (SUVpeak: R= −0.52; p=.026; SUVmean: R= −0.56; p=.026) in thromboelastography. Immunohistochemical analysis revealed FAP-positive fibroblasts in the infarct and border zone, and robust expression of α-smooth muscle actin and vimentin.Conclusions Simultaneous 68 Ga- FAPI PET/MR offers novel insights into the regional pattern of fibroblast activation in CHD, and the fibroblast activation protein signal is associated with abnormal wall motion. Trial registration ClinicalTrials: ClinicalTrials.gov ID: NCT05867589. Registered 01 May 2023, https://clinicaltrials.gov/study/NCT05867589.journal articl
Dual-Targeting of PD-L1 and Integrin αvβ3 for Preclinical PET Imaging of Cancer
No full textThe dual-targeting strategy has demonstrated advantages in enhancing tumor uptake, improving imaging contrast, and ultimately increasing tumor detection rate. PD-L1 is overexpressed on multiple tumor cells and regulated by αvβ3-integrin. In this study, a dual-targeting radiotracer, [64Cu]-PEG-RGD-TPP-1, is developedfor PET/CT imaging of both PD-L1 and αvβ3-integrin simultaneously, achieving high contrast, enhanced tumor uptake, and prolonged tumor retention time. [64Cu]-PEG-RGD-TPP-1 comprises the peptide TPP-1 and cyclic peptide c(RGDyC), linked via a PEG linker. The dual-targeting molecule had a moderate serum stability (≈60%) in vivo after 1 hr. This dual-targeting radiotracer is evaluated and compared with the single-targeting radiotracers [64Cu]-PEG-TPP-1 and [64Cu]-TPP-1. PET imaging and ex vivo biodistribution studies show that [64Cu]-PEG-RGD-TPP-1 exhibits higher tumor uptake than its single-targeting counterparts. Moreover, the dual-targeting radiotracer demonstrated potential for ultrasmall tumor imaging and could be combined with X-ray irradiation to further enhance PET imaging contrast, thereby improving tumor-targeting efficiency. These findings suggest that [64Cu]-PEG-RGD-TPP-1 is a promising noninvasive tracer for detecting tumors expressing PD-L1 and/or integrin avβ3, with the prospect of clinical implementation.journal articl
Nanoscale lithium evaporation and behavior in a superconducting linear accelerator of a future fusion neutron source A-FNS
No full textThe fusion neutron source (A-FNS) project is underway at the Rokkasho Institute for Fusion Energy, QST, in Japan. The A-FNS will conduct fusion neutron irradiation tests of fusion reactor materials. A high-intensity deuteron (D) beam accelerator with a Li target has been designed to produce large amounts of neutrons by the D-Li reaction.The A-FNS linac comprises a superconducting linac and a free-surface liquid Li target. Because the degradation of superconducting radio-frequency (SRF) cavities by Li contamination is of concern, a dedicated beam line design for reducing Li back streaming and a study of the Li behavior in ultra-high vacuum (UHV) are necessary. However, the relationship between the SRF performance and Li contamination remains unclear. To clarify this, we designed a nanoscale Li evaporation system to inject Li vapor into SRF cavities and investigated the behavior of the Li vapor.This paper reports the development and operational results of the nanoscale Li evaporation apparatus.journal articl
Estimation of the binding potential of the PET ligand [ 18F]FEDAC to translocator protein 18 kDa (TSPO) in the brain of experimental stroke model rats
No full textPurpose: Translocator protein 18 kDa (TSPO) is a biomarker for neuroinflammation, and [18F]FEDAC was developed as a clinically usable radioligand for its imaging. Here, quantitative PET analyses of [18F]FEDAC in the brain of transient middle cerebral artery occlusion (tMCAO) rats were conducted for the first time.Methods: Quantitative PET analysis was performed on rats subjected to tMCAO, with blood sampling also conducted as part of the study. To estimate the kinetic parameters of [18F]FEDAC, two-tissue compartment model (2TCM) and simplified reference tissue model (SRTM) analyses were conducted.Results: The input rate (K1) and distribution volume (VT) (a macroparameter consisting of the K1–k4 rate constants from 2TCM analysis) of [18F]FEDAC in the ipsilateral area of tMCAO rats were 0.38 ± 0.19 mL/cm3/min and 5.4 ± 2.7 mL/cm3, respectively, which are roughly twice as high as those in the contralateral area. These results strongly suggest that ipsilateral binding potential (BPND), a quantitative index derived from the VT ratio with respect to the reference region, depends not only on the binding of [18F]FEDAC to TSPO, but also on increases in the input rate from blood. Therefore, in SRTM analyses, we corrected apparent BPND using R1, an index for probe delivery. In validation studies, SRTM analysis with the corrected BPND (corBPND), using the cerebellum as a reference, showed a high correlation with direct BPND (k3/k4) in 2TCM analyses.Conclusion: The acquisition of quantitative PET images of TSPO distribution in the tMCAO rat brain was successfully achieved by scaling with corBPND.journal articl