p38 MAPK as a gatekeeper of reprogramming in mouse migratory primordial germ cells.

Mammalian germ cells are derived from primordial germ cells (PGCs) and ensure species continuity through generations. Unlike irreversible committed mature germ cells, migratory PGCs exhibit a latent pluripotency characterized by the ability to derive embryonic germ cells (EGCs) and form teratoma. Here, we show that inhibition of p38 mitogen-activated protein kinase (MAPK) by chemical compounds in mouse migratory PGCs enables derivation of chemically induced Embryonic Germ-like Cells (cEGLCs) that do not require conventional growth factors like LIF and FGF2/Activin-A, and possess unique naïve pluripotent-like characteristics with epiblast features and chimera formation potential. Furthermore, cEGLCs are regulated by a unique PI3K-Akt signaling pathway, distinct from conventional naïve pluripotent stem cells described previously. Consistent with this notion, we show by performing ex vivo analysis that inhibition of p38 MAPK in organ culture supports the survival and proliferation of PGCs and also potentially reprograms PGCs to acquire indefinite proliferative capabilities, marking these cells as putative teratoma-producing cells. These findings highlight the utility of our ex vivo model in mimicking in vivo teratoma formation, thereby providing valuable insights into the cellular mechanisms underlying tumorigenesis. Taken together, our research underscores a key role of p38 MAPK in germ cell development, maintaining proper cell fate by preventing unscheduled pluripotency and teratoma formation with a balance between proliferation and differentiation.

Development of a chemically disclosed serum-free medium for mouse pluripotent stem cells.

Mouse embryonic stem cells (mESCs) have been widely used as a model system to study the basic biology of pluripotency and to develop cell-based therapies. Traditionally, mESCs have been cultured in a medium supplemented with fetal bovine serum (FBS). However, serum with its inconsistent chemical composition has been problematic for reproducibility and for studying the role of specific components. While some serum-free media have been reported, these media contain commercial additives whose detailed components have not been disclosed. Recently, we developed a serum-free medium, DA-X medium, which can maintain a wide variety of adherent cancer lines. In this study, we modified the DA-X medium and established a novel serum-free condition for both naïve mESCs in which all components are chemically defined and disclosed (DA-X-modified medium for robust growth of pluripotent stem cells: DARP medium). The DARP medium fully supports the normal transcriptome and differentiation potential in teratoma and the establishment of mESCs from blastocysts that retain the developmental potential in all three germ layers, including germ cells in chimeric embryos. Utility of chemically defined DA-X medium for primed mouse epiblast stem cells (mEpiSCs) revealed that an optimal amount of cholesterol is required for the robust growth of naïve-state mESCs, but is dispensable for the maintenance of primed-state mEpiSCs. Thus, this study provides reliable and reproducible culture methods to investigate the role of specific components regulating self-renewal and pluripotency in a wide range of pluripotent states.

Computational Fluid Dynamics Analysis of Trigeminal Neuralgia Associated with the Vertebral Artery: A Report of Two Cases.

Trigeminal neuralgia is a nerve disorder that causes unilateral severe facial pain. The clinical features of trigeminal neuralgia are agonizing, paroxysmal, anticipated in one or more divisions of the trigeminal nerve, with repetitive bursts of a few seconds, exacerbated by cutaneous stimuli. Microvascular decompression is proven effective, resulting in a positive outcome. Here, we report two cases of trigeminal neuralgia associated with the vertebral artery, who underwent endoscopic microvascular decompression. This case report aims to show the benefit of computational fluid dynamics evaluation of the neurovascular contact and its effect on change in wall shear stress magnitude of the offending vertebral artery after surgical management with microvascular decompression.

The ensured proliferative capacity of myoblast in serum-reduced conditions with Methyl-ß-cyclodextrin.

To produce muscle fibers for cultured meat on a large scale, it is important to expand myoblasts in a serum-reduced or serum-free medium to avoid cost, ethical, and environmental issues. Myoblasts such as C2C12 cells differentiate quickly into myotubes and lose their ability to proliferate when the serum-rich medium is replaced with a serum-reduced medium. This study demonstrates that Methyl-ß-cyclodextrin (MßCD), a starch-derived agent that depletes cholesterol, can inhibit further differentiation of myoblasts at the MyoD-positive stage by reducing plasma membrane cholesterol on C2C12 cells and primary cultured chick muscle cells. Furthermore, MßCD efficiently blocks cholesterol-dependent apoptotic cell death of myoblasts, which is one of the mechanisms by which it inhibits the differentiation of C2C12 myoblast cells, as dead cells of myoblast are necessary for the fusion of adjacent myoblasts during the differentiation process into myotubes. Importantly, MßCD maintains the proliferative capacity of myoblasts only under differentiation conditions with a serum-reduced medium, suggesting that its mitogenic effect is due to its inhibitory effect on myoblast differentiation into myotube. In conclusion, this study provides significant insights into ensuring the proliferative capacity of myoblasts in a future serum-free condition for cultured meat production.

Preoperative 3D Image Evaluation of EC-IC Bypass by 3D Visualization Analysis Software Amira®.

Background: Careful evaluation of the preoperative imaging for extracranial-intracranial bypass performed for conditions like intracranial stenosis and Moya disease is important. The traditional use of 2D imaging has a significant limitation for neurosurgeons, primarily to determine the optimal location of the recipient artery for performing the surgical bypass. Therefore, many neurosurgeons use 3D angiograms more frequently to overcome these shortcomings. Materials And Methods: We performed the preoperative evaluation of the possibility of performing an anastomosis between the superficial temporal artery and the middle cerebral artery (STA-MCA) bypass by synthesizing images of computerized tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) using Amira® of 3D visualization analysis software (Thermo Scientific Co.). Results: The 3D images prepared before surgery using this software showed good agreement with the intraoperative findings. Conclusion: Preoperative image processing using tools like Amira provide optimal information for good planning and communication for performing STA-MCA bypass and may become a helpful tool.

Functional near-infrared spectroscopy study of the neural correlates between auditory environments and intellectual work performance.

INTRODUCTION: Many people spend a considerable amount of time performing intellectual activities within auditory environments that affect work efficiency. To investigate auditory environments that improve working efficiency, we investigated the relationship between brain activity and performance of the number memory task in environments with and without white noise using functional near-infrared spectroscopy (fNIRS). METHODS: Twenty-nine healthy subjects (aged 21.9 ± 1.4 years) performed the number memory task in both the white noise and silent environments. Cerebral blood flow changes during the task were measured using an ETG-7100 fNIRS system (Hitachi, Ltd., Tokyo, Japan). The psychological states of the subjects were also estimated by subjective ratings of the pleasantness of the auditory environment. Then, they were divided into three groups based on their task scores. The differences in the cerebral blood flow (CBF) changes, functional connection strength, and the subjects' feelings of pleasantness to the noise between the subject groups were analyzed and discussed. RESULTS: The first group felt that the white noise was pleasant, which strengthened the bilateral functional connections between the brain regions related to the memory task. Therefore, the subjects' task performance improved in the white noise environment. Although the second group felt that the white noise was uncomfortable, the frontal regions related to attention control were more activated in the white noise environment to sustain the task performance in the noisy environment. The third group felt that the white noise was unpleasant, and their CBF decreased in that environment, which was associated with deteriorated task performance. CONCLUSIONS: Task performance was closely related to the subjects' feelings of pleasantness to the noise. The results of the analysis of the CBF changes and functional connectivity suggested that the effects of the white noise on brain activity differed among the three groups.