Sex–specific effects of carotenoid intake on the immunological response to allografts in guppies (\u3cem\u3ePoecilia reticulata\u3c/em\u3e)

Rarely are the evolutionary origins of mate preferences known, but, recently, the preference of female guppies (Poecilia reticulata) for males with carotenoid‐based sexual coloration has been linked to a sensory bias that may have originally evolved for detecting carotenoid‐rich fruits. If carotenoids enhance the immune systems of these fishes, as has been suggested for other species, this could explain the origin of the attraction to orange fruits as well as the maintenance of the female preference for orange males. We used the classic immunological technique of tissue grafting to assay a component of the immune response of guppies raised on two different dietary levels of carotenoids. Individual scales were transplanted between pairs of unrelated fishes, creating reciprocal allografts. Transplanted scales were scored on a six‐point rejection scale every day for 10 days. Five days later, the same pairs of fishes received a second set of allografts and were scored again. Compared with low‐carotenoid‐diet males, high‐carotenoid‐diet males mounted a significantly stronger rejection response to the second allograft but not to the first allograft. High‐carotenoid‐diet females, however, showed no improvement in graft rejection compared with low‐carotenoid‐diet females. To our knowledge, this is the first experimental evidence for sex‐specific effects of carotenoid consumption on the immune system of a species with carotenoid‐based sexual coloration. These results are consistent with the hypothesis that the mate preference for carotenoid coloration is maintained by the benefits to females of choosing healthy mates, but they cast doubt on the idea that the benefits of carotenoid consumption, per se, could account for the origin of the preference. The sex‐specificity of carotenoid effects on allograft rejection in guppies provides indirect support for the general hypothesis that males pay an immunological cost for sexual ornamentation

Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson’s disease

Background: Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson’s disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD. Results: Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively. Conclusion: Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment

Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus

This work has been supported by the MRC and the University of Aberdeen (MRC Centre for Medical Mycology) and by the Wellcome Trust Strategic Award - Medical Mycology Fungal Immunology (SFB, JMB, JK, AW). A special thank you is given to the support from the Chloe fund. TMH is supported by a grant from the National institute of health (NIH, code RO1 093808) and the Memorial Sloan Kettering Cancer Center is supported by NIH grant P30 CA008748. Additionally, TMH is an investigator in the Pathogenesis of Infectious Disease supported by the Burroughs Wellcome Fund. We wish to thank the Aberdeen Microscopy and Histology Facility for their help and support.Peer reviewedPublisher PD

Striatal Cdk5-pTyr15

Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5), which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) at Thr75 in the striatum. c-Abelson tyrosine kinase (c-Abl) is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5) and thereby facilitates the Cdk5 activity. We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15) is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum

新規な磁気共鳴イメージングを用いたメニエール病の高精度診断法

Background: Pathologically, Meniere's disease symptoms are considered to be associated with endolymphatic hydrops. Examinations revealing endolymphatic hydrops can be useful for accurate Meniere's disease diagnosis. We previously reported a quantitative method for evaluating endolymphatic hydrops, i.e., by measuring the volume of the endolymphatic space using three-dimensional magnetic resonance imaging (MRI) of the inner ear. This study aimed to confirm the usefulness of our methods for diagnosing Meniere's disease. Here, we extracted new explanatory factors for diagnosing Meniere's disease by comparing the volume of the endolymphatic space between healthy volunteers and patients with Meniere's disease. Additionally, we validated our method by comparing its diagnostic accuracy with that of the conventional method. Methods and Findings: This is a prospective diagnostic accuracy study performed at vertigo/dizziness centre of our university hospital, a tertiary hospital. Eighty-six patients with definite unilateral Meniere's disease and 47 healthy volunteers (25 and 33 males, and 22 and 53 females in the control and patient groups, respectively) were enrolled. All participants underwent 3-Tesla MRI 4 h after intravenous injection of gadolinium to reveal the endolymphatic space. The volume of the endolymphatic space was measured and a model for Meniere's disease diagnosis was constructed and compared with models using conventional criteria to confirm the effectiveness of the methods used. The area under the receiver operating characteristic curve of the method proposed in this study was excellent (0.924), and significantly higher than that derived using the conventional criteria (0.877). The four indices, sensitivity, specificity, positive predictive value, and negative predictive value, were given at the threshold; all of these indices achieved higher scores for the 3D model compared to the 2D model. Cross-validation of the models revealed that the improvement was due to the incorporation of the semi-circular canals. Conclusions: Our method showed high diagnostic accuracy for Meniere's disease. Additionally, we revealed the importance of observing the semi-circular canals for Meniere's disease diagnosis. The proposed method can contribute toward providing effective symptomatic relief in Meniere's disease.博士（医学）・甲第807号・令和3年12月21日Copyright © 2021 Ito, Inoue, Inui, Miyasaka, Yamanaka, Kichikawa, Takeda, Kasahara, Kitahara and Naganawa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications

To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E) T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference) and its graphical form (scatter plot). In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication

Reasons for the delays in the definitive diagnosis of lung cancer for more than one year from the recognition of abnormal chest shadows

金沢大学医薬保健研究域医学系Objective. Primary lung cancer generally has a poor prognosis if not diagnosed at an early stage. But some lung cancers grow very slowly. In particular, adenocarcinoma is sometimes observed for years with no change of tumor size. In this study, we examined the reasons for the delays in reaching a definitive diagnosis of lung cancer. Methods. We retrospectively reviewed primary lung cancer cases between January 1995 and December 1999 and examined those whose definitive diagnoses were delayed for more than a year. Results. A total of 222 primary lung cancers were diagnosed. Of those, 19 patients (group A, 8.6%) were diagnosed after more than a year, and the other 203 (group B, 91.4%) were diagnosed within one year. The proportion of women in group A was significantly higher than that in group B (p<0.05). The mean age of group A was significantly younger than that of group B (p<0.05). The Brinkman Index of group A was significantly lower than that of group B (p<0.05). The histologic types were significantly different between the two groups (p<0.05). In group A, 18 patients (94.7%) had adenocarcinomas. Five primary reasons for the delays in group A were identified: 1) Four patients were tentatively diagnosed as inflammation or benign tumor on CT and were consequently not followed-up. 2) The chest CT shadows in 6 patients were suspected lung cancers but transbronchial lung biopsy findings did not show malignancy. 3) Four patients were tentatively diagnosed as inflammation or benign tumor on CT, but the tumors showed only very slow growth or no change at all. 4) The chest CT shadows of 2 patients were suspected lung cancer, but the patients refused to undergo video-assisted thoracic surgery (VATS) or closer examination. 5) Three patients did not consult medical facilities for a second examination. Conclusions. Many of the adenocarcinomas reviewed in our study grew slowly or remained unchanged for years. Doctors are mainly responsible for the delays in the definitive diagnosis and should aggressively perform VATS or closer examinations without hesitation

Acute eosinophilic pneumonia following cigarette smoking: A case report including cigarette-smoking challenge test

金沢大学医薬保健研究域医学系A 21-year-old woman presented with acute progressive dyspnea. Chest computed tomography (CT) revealed diffuse bilateral infiltrates. Based on the results of transbronchial lung biopsy (TBLB) and bronchoalveolar lavage fluid (BALF) and her clinical course, she was diagnosed as having acute eosinophilic pneumonia. We suspected that the disease was related to smoking because she had started smoking ten days before the onset of symptoms. Therefore, a cigarette-smoking challenge test was done with the patient\u27s informed consent. After the challenge, eosinophilic pneumonia was documented by BALF and TBLB findings, which were similar to those detected on admission, without significant radiographic findings

Application of gas-cooled Accelerator Driven System (ADS) transmutation devices to sustainable nuclear energy development

The conceptual design of a pebble bed gas-cooled transmutation device is shown with the aim to evaluate its potential for its deployment in the context of the sustainable nuclear energy development, which considers high temperature reactors for their operation in cogeneration mode, producing electricity, heat and Hydrogen. As differential characteristics our device operates in subcritical mode, driven by a neutron source activated by an accelerator that adds clear safety advantages and fuel flexibility opening the possibility to reduce the nuclear stockpile producing energy from actual LWR irradiated fuel with an efficiency of 45?46%, either in the form of Hydrogen, electricity, or both