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  1. Article ; Online: Role of dopamine neuron activity in Parkinson's disease pathophysiology.

    Rademacher, Katerina / Nakamura, Ken

    Experimental neurology

    2023  Volume 373, Page(s) 114645

    Abstract: Neural activity is finely tuned to produce normal behaviors, and disruptions in activity likely occur early in the course of many neurodegenerative diseases. However, how neural activity is altered, and how these changes influence neurodegeneration is ... ...

    Abstract Neural activity is finely tuned to produce normal behaviors, and disruptions in activity likely occur early in the course of many neurodegenerative diseases. However, how neural activity is altered, and how these changes influence neurodegeneration is poorly understood. Here, we focus on evidence that the activity of dopamine neurons is altered in Parkinson's disease (PD), either as a compensatory response to degeneration or as a result of circuit dynamics or pathologic proteins, based on available human data and studies in animal models of PD. We then discuss how this abnormal activity may augment other neurotoxic phenomena in PD, including mitochondrial deficits, protein aggregation and spread, dopamine toxicity, and excitotoxicity. A more complete picture of how activity is altered and the resulting effects on dopaminergic neuron health and function may inform future therapeutic interventions to target and protect dopamine neurons from degeneration.
    MeSH term(s) Animals ; Humans ; Parkinson Disease/pathology ; Dopaminergic Neurons/pathology ; Dopamine/metabolism ; Neurodegenerative Diseases/pathology ; Mitochondria/metabolism ; Disease Models, Animal
    Chemical Substances Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2023-12-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207148-4
    ISSN 1090-2430 ; 0014-4886
    ISSN (online) 1090-2430
    ISSN 0014-4886
    DOI 10.1016/j.expneurol.2023.114645
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 184: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  2. Article ; Online: Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production.

    Bennett, Neal K / Lee, Megan / Orr, Adam L / Nakamura, Ken

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 3, Page(s) e2307904121

    Abstract: Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are ... ...

    Abstract Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS-based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III, and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits-including
    MeSH term(s) Reactive Oxygen Species/metabolism ; Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/metabolism ; Adenosine Triphosphate/metabolism ; Oxidative Stress
    Chemical Substances Reactive Oxygen Species ; Mitochondrial Proteins ; Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2307904121
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    In stock of ZB MED Cologne/Königswinter

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  3. Article ; Online: An Isolated Laminar Osteoma Arising in the Maxillary Sinus.

    Taketomi, Takaharu / Imayama, Kouhei / Nakamura, Ken / Kusukawa, Jingo

    The American journal of case reports

    2023  Volume 24, Page(s) e938904

    Abstract: BACKGROUND Osteomas are benign tumors characterized by proliferation of dense or trabecular bone. Most osteomas of the head and neck occur in the mandible, they rarely occur in the maxillary sinus, and free osteomas are extremely rare. While usually ... ...

    Abstract BACKGROUND Osteomas are benign tumors characterized by proliferation of dense or trabecular bone. Most osteomas of the head and neck occur in the mandible, they rarely occur in the maxillary sinus, and free osteomas are extremely rare. While usually detected incidentally on plain radiographs, symptoms appear when the osteoma obstructs the sinus orifice or invades the adjacent orbit or intracranial structures. Herein, we report a case of a patient with an isolated laminar osteoma arising in the maxillary sinus. CASE REPORT A 52-year-old man presented to our hospital with a radiopaque mass in the right maxillary sinus. An oval mass of size 2.7×2.3 cm was observed in the right maxillary sinus on computed tomography, and no sinusitis was present. Under general anesthesia, the mass was removed orally via the modified Caldwell-Luc method. Histopathologic examination revealed layered compact bony tissue covered by the sinus membrane. The mass was free from the inferior wall of the right maxillary sinus, and a part of the mass was covered by the sinus membrane. The postoperative course was uneventful, and no recurrence was noted after 5 years. CONCLUSIONS We experienced a case of an extremely rare osteoma in the maxillary sinus. The osteoma was solitary and free within the maxillary sinus. The treatment performed was surgical excision using the modified Caldwell-Luc method. The cause of the free osteoma was thought to be odontogenic maxillary sinusitis caused by apical periodontitis of the nearby tooth.
    MeSH term(s) Male ; Humans ; Middle Aged ; Maxillary Sinus/diagnostic imaging ; Maxillary Sinus/pathology ; Tomography, X-Ray Computed ; Radiography ; Osteoma/diagnostic imaging ; Osteoma/surgery ; Anesthesia, General ; Paranasal Sinus Neoplasms
    Language English
    Publishing date 2023-03-27
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2517183-5
    ISSN 1941-5923 ; 1941-5923
    ISSN (online) 1941-5923
    ISSN 1941-5923
    DOI 10.12659/AJCR.938904
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  4. Article ; Online: Protocol to combine brain sections from multiple mice into a single block for spatial transcriptomic analyses.

    Sei, Yoshitaka J / Chaumeil, Myriam M / Nakamura, Ken

    STAR protocols

    2023  Volume 4, Issue 4, Page(s) 102617

    Abstract: Spatial transcriptomics couples visual spatial markers with gene expression levels, but slide space and cost limit the number of samples that can be processed. Here, we present a protocol for mounting brains from multiple mice onto a single capture area ... ...

    Abstract Spatial transcriptomics couples visual spatial markers with gene expression levels, but slide space and cost limit the number of samples that can be processed. Here, we present a protocol for mounting brains from multiple mice onto a single capture area of a spatial transcriptomics slide. We describe steps for conjoining frozen hippocampal sections from different brains into a single cryostat block, reducing the quantity of reagents required. This protocol is applicable to a range of existing spatial genomics platforms. For complete details on the use and execution of this protocol, please refer to Li et al. (2023).
    MeSH term(s) Animals ; Mice ; Gene Expression Profiling ; Transcriptome/genetics ; Brain ; Genomics ; Hippocampus
    Language English
    Publishing date 2023-09-23
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102617
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  5. Article ; Online: Mice with disrupted mitochondria used to model Parkinson's disease.

    Doric, Zak / Nakamura, Ken

    Nature

    2021  Volume 599, Issue 7886, Page(s) 558–560

    MeSH term(s) Animals ; Mice ; Mitochondria ; Neurons/metabolism ; Parkinson Disease/metabolism
    Language English
    Publishing date 2021-11-03
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-021-02955-z
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    Zs.A 26: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 9: Show issues
    Zs.MO 244: Show issues

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  6. Article: Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production.

    Bennett, Neal K / Lee, Megan / Orr, Adam L / Nakamura, Ken

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are ... ...

    Abstract Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS- based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits-including NDUFA8, NDUFB4, and NDUFS8-decreased complex I activity, mitochondria-derived ATP and supercomplex level, but knockdown of these genes had differential effects on ROS. Conversely, we found an essential role for ether lipids in the dynamic regulation of mitochondrial ROS levels independent of ATP. Thus, our results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.
    Language English
    Publishing date 2023-10-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.14.562276
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  7. Article: [Staged Hybrid Repair of Extensive Thoracic Aortic Aneurysm with Right Aortic Arch and Isolated Left Subclavian Artery:Report of a Case].

    Niki, Taiki / Yoshida, Kazufumi / Nakamura, Ken / Kinoshita, Makoto / Koyama, Tadaaki

    Kyobu geka. The Japanese journal of thoracic surgery

    2023  Volume 76, Issue 2, Page(s) 132–135

    Abstract: A 69-year-old male was referred to our hospital due to extensive thoracic aortic aneurysm with right aortic arch and isolated left subclavian artery. We chose staged hybrid repair to avoid the risk of spinal cord injury and bilateral recurrent nerve ... ...

    Abstract A 69-year-old male was referred to our hospital due to extensive thoracic aortic aneurysm with right aortic arch and isolated left subclavian artery. We chose staged hybrid repair to avoid the risk of spinal cord injury and bilateral recurrent nerve paralysis. First, ascending aorta replacement with elephant trunk and reconstruction of the cervical branches were underwent. Second, we performed the thoracic endovascular aortic repair for aortic arch and descending aortic aneurysm. The postoperative course was satisfactory and, computed tomography (CT) showed successful aortic repair without any type of endoleak. He was discharged on the ninth day after the second operation. To our knowledge, this is the first report of surgical repair for an aortic aneurysm with right aortic arch and isolated subclavian artery.
    MeSH term(s) Male ; Humans ; Aged ; Aorta, Thoracic/diagnostic imaging ; Aorta, Thoracic/surgery ; Subclavian Artery/diagnostic imaging ; Subclavian Artery/surgery ; Aortic Aneurysm, Thoracic/diagnostic imaging ; Aortic Aneurysm, Thoracic/surgery ; Aortic Aneurysm/surgery ; Blood Vessel Prosthesis Implantation ; Treatment Outcome ; Stents ; Endovascular Procedures/methods
    Language Japanese
    Publishing date 2023-01-31
    Publishing country Japan
    Document type Case Reports ; English Abstract ; Journal Article
    ZDB-ID 603899-2
    ISSN 0021-5252
    ISSN 0021-5252
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Reader Response: Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial.

    Kang, Un Jung / Nakamura, Ken / Zhuang, Xiaoxi

    Neurology

    2022  Volume 99, Issue 6, Page(s) 258–259

    MeSH term(s) Genetic Therapy/adverse effects ; Humans ; Levodopa ; Parkinson Disease/genetics ; Parkinson Disease/therapy
    Chemical Substances Levodopa (46627O600J)
    Language English
    Publishing date 2022-08-10
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000201002
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    Ui II Zs.153: Show issues Location:
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  9. Article ; Online: Staged graft replacement with thoracic endovascular aneurysm repair for an extensive thoracoabdominal aortic aneurysm after total arch replacement.

    Yoshida, Kazufumi / Nakamura, Ken / Ishigami, Masanosuke / Kinoshita, Makoto / Koyama, Tadaaki

    Journal of cardiothoracic surgery

    2022  Volume 17, Issue 1, Page(s) 20

    Abstract: Background: Open surgery for thoracoabdominal aortic aneurysm is highly invasive. Staged repair for extensive TAAA is effective because it has low morbidity and mortality, and preserves spinal cord perfusion. An initial total arch replacement can create ...

    Abstract Background: Open surgery for thoracoabdominal aortic aneurysm is highly invasive. Staged repair for extensive TAAA is effective because it has low morbidity and mortality, and preserves spinal cord perfusion. An initial total arch replacement can create a proximal landing zone for thoracic endovascular aneurysm repair.
    Case presentation: We performed a staged hybrid thoracoabdominal aortic aneurysm repair after total arch replacement, which consisted of a primary open repair procedure as Crawford Extent III and IV thoracoabdominal aortic aneurysms, and a secondary thoracic endovascular aneurysm repair for the residual lesions for four patients. No spinal cord injury was observed. In one patient, the residual descending aortic aneurysm ruptured six months after the primary open surgery.
    Conclusions: Overall, staged hybrid repair is effective and shows low morbidity and mortality. Secondary thoracic endovascular aneurysm repair should be performed as soon as possible to reduce the risk of residual aneurysm rupture.
    MeSH term(s) Aneurysm, Dissecting/surgery ; Aortic Aneurysm, Abdominal/surgery ; Aortic Aneurysm, Thoracic/complications ; Aortic Aneurysm, Thoracic/diagnostic imaging ; Aortic Aneurysm, Thoracic/surgery ; Blood Vessel Prosthesis Implantation/methods ; Endovascular Procedures/adverse effects ; Humans ; Postoperative Complications/etiology ; Retrospective Studies ; Treatment Outcome
    Language English
    Publishing date 2022-02-21
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2227224-0
    ISSN 1749-8090 ; 1749-8090
    ISSN (online) 1749-8090
    ISSN 1749-8090
    DOI 10.1186/s13019-022-01764-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: On the reaction-diffusion type modelling of the self-propelled object motion.

    Nagayama, Masaharu / Monobe, Harunori / Sakakibara, Koya / Nakamura, Ken-Ichi / Kobayashi, Yasuaki / Kitahata, Hiroyuki

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 12633

    Abstract: In this study, we propose a mathematical model of self-propelled objects based on the Allen-Cahn type phase-field equation. We combine it with the equation for the concentration of surfactant used in previous studies to construct a model that can handle ... ...

    Abstract In this study, we propose a mathematical model of self-propelled objects based on the Allen-Cahn type phase-field equation. We combine it with the equation for the concentration of surfactant used in previous studies to construct a model that can handle self-propelled object motion with shape change. A distinctive feature of our mathematical model is that it can represent both deformable self-propelled objects, such as droplets, and solid objects, such as camphor disks, by controlling a single parameter. Furthermore, we demonstrate that, by taking the singular limit, this phase-field based model can be reduced to a free boundary model, which is equivalent to the [Formula: see text]-gradient flow model of self-propelled objects derived by the variational principle from the interfacial energy, which gives a physical interpretation to the phase-field model.
    Language English
    Publishing date 2023-08-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-39395-w
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