Effects of static interventions on disuse atrophy of the rat soleus muscle at different sites along its longitudinal axis.

13301甲第4303号博士（保健学）金沢大学博士論文本文Full 以下に掲載：Journal of Physical Therapy Science 27(7) pp.2317-2321 2015. JPTS. 共著者：Ryo Miyachi, Toshiaki Yamazak

Lumbar motor control & perceptual awareness

Purpose : The purpose of this study was to clarify the differences in lumbar spine and hip joint motor control ability (MCA) in prone hip extension (PHE) between individuals with and without low back pain (LBP). It also aimed to determine the relationship between lumbar spine and hip joint MCA and lumbar perceptual awareness in individuals with LBP. Methods : In total, 78 university students (20 with LBP and 58 without) were included in the study. The MCA of the lumbar spine and hip joint in PHE and perceptual awareness were evaluated. The MCA of the lumbar spine and hip joint was measured using a wearable sensor. Subsequently, a comparison of the MCA of the lumbar spine and hip joints of the participants and the relationship between MCA and lumbar perceptual awareness were examined. Results : The MCA of the LBP group was higher than that of the non-LBP group in motion on the sagittal plane. In addition, perceptual awareness was negatively correlated with MCA in the sagittal plane in the lumbar spine. Conclusion : People with LBP had higher lumbar spine and hip joint MCA than those without LBP. Perceptual awareness was associated with lumbar spine and hip joint MCA in people with LBP

H3K9 Demethylases JMJD1A and JMJD1B Control Prospermatogonia to Spermatogonia Transition in Mouse Germline

Histone H3 lysine 9 (H3K9) methylation is dynamically regulated by methyltransferases and demethylases. In spermatogenesis, prospermatogonia differentiate into differentiating or undifferentiated spermatogonia after birth. However, the epigenetic regulation of prospermatogonia to spermatogonia transition is largely unknown. We found that perinatal prospermatogonia have extremely low levels of di-methylated H3K9 (H3K9me2) and that H3K9 demethylases, JMJD1A and JMJD1B, catalyze H3K9me2 demethylation in perinatal prospermatogonia. Depletion of JMJD1A and JMJD1B in the embryonic germline resulted in complete loss of male germ cells after puberty, indicating that H3K9me2 demethylation is essential for male germline maintenance. JMJD1A/JMJD1B-depleted germ cells were unable to differentiate into functional spermatogonia. JMJD1 isozymes contributed to activation of several spermatogonial stem cell maintenance genes through H3K9 demethylation during the prospermatogonia to spermatogonia transition, which we propose is key for spermatogonia development. In summary, JMJD1A/JMJD1B-mediated H3K9me2 demethylation promotes prospermatogonia to differentiate into functional spermatogonia by establishing proper gene expression profiles

Usefulness of the Pipeline Embolic Device for Large and Giant Carotid Cavernous Aneurysms

PurposeConventional coil embolization for large carotid cavernous aneurysms (CCAs) has limited utility due to its inability to prevent recurrences and reduce mass effect. Trapping of the parent artery may have a risk of ischemic complications due to intracranial perfusion disorders. We successfully treated 24 patients with large CCAs using a flow diverter (Pipeline™ embolic device: PED), and this report discusses the safety and efficacy of this method.Materials and MethodsTwenty four patients (23 females, mean age 71.5 years old) with large CCAs, including 6 giant CCAs, were treated with a PED over three years. Under sufficient dual anti-platelet management, the PED was deployed over the orifice of the aneurysm. Two patients required multiple telescoping stents. Clinical and radiological states were checked with MRI at 1, 3 and 6 months post-surgically. Angiographic follow-up was performed at 6 months.ResultsIn all patients, PED was appropriately deployed. Stagnation of contrast with eclipse signs was observed post-angiogram in 21 cases. One patient requiring 5 telescoping stents experienced temporary ischemic symptoms. Fourteen patients experienced improvement of ocular motor impairment deficiency, including 6 patients who recovered. Angiograms at 6 months follow-up showed complete occlusion in 63% (12/19) of patients, and MRI showed reduction of aneurysm volume in 89% (17/19) of patients.ConclusionFlow diverters for large CCAs showed promising clinical and radiological efficacy. They can shrink the aneurysm and improve symptoms without sacrificing the parent artery. It will be necessary to summarize the cases and to verify the long-term results

Tuning of Sry expression by H3K9 methylation and demethylation

Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the Sry locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous GLP mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring Sry expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of Sry expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance

Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis

Histone H3 lysine 9 (H3K9) methylation is unevenly distributed in mammalian chromosomes. However, the molecular mechanism controlling the uneven distribution and its biological significance remain to be elucidated. Here, we show that JMJD1A and JMJD1B preferentially target H3K9 demethylation of gene-dense regions of chromosomes, thereby establishing an H3K9 hypomethylation state in euchromatin. JMJD1A/JMJD1B-deficient embryos died soon after implantation accompanying epiblast cell death. Furthermore, combined loss of JMJD1A and JMJD1B caused perturbed expression of metabolic genes and rapid cell death in embryonic stem cells (ESCs). These results indicate that JMJD1A/JMJD1B-meditated H3K9 demethylation has critical roles for early embryogenesis and ESC maintenance. Finally, genetic rescue experiments clarified that H3K9 overmethylation by G9A was the cause of the cell death and perturbed gene expression of JMJD1A/JMJD1B-depleted ESCs. We summarized that JMJD1A and JMJD1B, in combination, ensure early embryogenesis and ESC viability by establishing the correct H3K9 methylated epigenome

Vasculature-driven stem cell population coordinates tissue scaling in dynamic organs

Stem cell (SC) proliferation and differentiation organize tissue homeostasis. However, how SCs regulate coordinate tissue scaling in dynamic organs remain unknown. Here, we delineate SC regulations in dynamic skin. We found that interfollicular epidermal SCs (IFESCs) shape basal epidermal proliferating clusters (EPCs) in expanding abdominal epidermis of pregnant mice and proliferating plantar epidermis. EPCs consist of IFESC-derived Tbx3⁺–basal cells (Tbx3⁺-BCs) and their neighboring cells where Adam8–extracellular signal–regulated kinase signaling is activated. Clonal lineage tracing revealed that Tbx3⁺-BC clones emerge in the abdominal epidermis during pregnancy, followed by differentiation after parturition. In the plantar epidermis, Tbx3⁺-BCs are sustained as long-lived SCs to maintain EPCs invariably. We showed that Tbx3⁺-BCs are vasculature-dependent IFESCs and identified mechanical stretch as an external cue for the vasculature-driven EPC formation. Our results uncover vasculature-mediated IFESC regulations, which explain how the epidermis adjusts its size in orchestration with dermal constituents in dynamic skin

Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow

骨髄のNK細胞の分化に造血細胞が産生するIL-15が必須である --2種類の局在を示すNK細胞の新規分化モデル--. 京都大学プレスリリース. 2023-09-20.Natural killer (NK) cells are innate immune cells critical for protective immune responses against infection and cancer. Although NK cells differentiate in the bone marrow (BM) in an interleukin-15 (IL-15)-dependent manner, the cellular source of IL-15 remains elusive. Using NK cell reporter mice, we show that NK cells are localized in the BM in scattered and clustered manners. NK cell clusters overlap with monocyte and dendritic cell accumulations, whereas scattered NK cells require CXCR4 signaling. Using cell-specific IL-15-deficient mice, we show that hematopoietic cells, but not stromal cells, support NK cell development in the BM through IL-15. In particular, IL-15 produced by monocytes and dendritic cells appears to contribute to NK cell development. These results demonstrate that hematopoietic cells are the IL-15 niche for NK cell development in the BM and that BM NK cells are present in scattered and clustered compartments by different mechanisms, suggesting their distinct functions in the immune response

間歇的伸張運動によるラットヒラメ筋廃用性萎縮の変化: 筋萎縮抑制効果の経時的変化に関して

〔目的〕廃用性萎縮筋に対する間歇的伸張運動の筋萎縮抑制効果を，経時的および長軸部位別に検討すること．〔対象と方法〕対象は，8週齢Wistar系ラットのヒラメ筋とした．通常飼育をするC群，後肢懸垂を行うHS群，後肢懸垂中に伸張運動を行うST群に分けた．さらにそれぞれ0・3・7・10・14日時点に群分けした．実験期間終了後，筋の近位・中央・遠位部で凍結切片を作成，HE染色を行い，筋線維横断面積（CSA）を測定した．〔結果〕伸張運動開始14日目でHS 群のCSAがST群と比較し有意に高値を示した．また，14日目のST群で，中央・遠位部での筋線維横断面積の減少率がHS群に比べて小さかった．〔結語〕廃用性萎縮筋は伸張運動により経時的に変化し，萎縮抑制効果は長軸部位により異なることが示唆された． [Purpose] The purpose of this study was to investigate the effects of intermittent stretching exercise on disuse atrophy of the rat soleus muscle with respect to site and the change over time in the inhibitory effect on atrophy. [Subjects and Methods] Eighty-three 8-week-old male Wistar rats were divided into 3 groups: a control group which was reared under standard conditions (C0/3/7/10/14), a hind-limb suspension group (HS3/7/10/14), and a stretching exercise group (ST3/7/10/14). After the completion of each experimental period the soleus muscle was cut into proximal, middle, and distal samples, which were stained with hematoxylin and eosin, and the cross-sectional area (CSA) was measured. [Results] The CSA of ST14 was significantly greater than that of HS14. The reduction rate of the CSA in the middle and distal regions of ST14 was small compared to that of HS14. [Conclusion] The results suggest that disuse atrophy is altered over time by stretching exercise, and that there are differences in effect among the longitudinal sites of the soleus muscle.出版者照会後に全文公