Essential Roles of Exocyst Complex Component 3-like 2 on Cardiovascular Development in Mice

滋賀医科大学博士（医学）application/pdfAngiogenesis is a process to generate new blood vessels from pre-existing vessels and to maintain vessels, and plays critical roles in normal development and disease. However, the molecular mechanisms underlying angiogenesis are not fully understood. This study examined the roles of exocyst complex component (Exoc) 3-like 2 (Exoc3l2) during development in mice. We found that Exoc3l1, Exoc3l2, Exoc3l3 and Exoc3l4 are expressed abundantly in endothelial cells at embryonic day 8.5. The generation of Exoc3l2 knock-out (KO) mice showed that disruption of Exoc3l2 resulted in lethal in utero. Substantial numbers of Exoc3l2 KO embryos exhibited hemorrhaging. Deletion of Exoc3l2 using Tie2-Cre transgenic mice demonstrated that Exoc3l2 in hematopoietic and endothelial lineages was responsible for the phenotype. Taken together, these findings reveal that Exoc3l2 is essential for cardiovascular and brain development in mice.Thesis or Dissertation令和4年度doctoral thesi

Lyman Break Galaxies at z∼5z\sim5: Rest-Frame UV Spectra

We report initial results for spectroscopic observations of candidates of Lyman Break Galaxies (LBGs) at $z\sim5$ in a region centered on the Hubble Deep Field-North by using the Faint Object Camera and Spectrograph attached to the Subaru Telescope. Eight objects with $I_C\leq25.0$ mag, including one AGN, are confirmed to be at $4.5<z<5.2$. The rest-frame UV spectra of seven LBGs commonly show no or weak Lyalpha emission line (rest-frame equivalent width of 0-10\AA) and relatively strong low-ionization interstellar metal absorption lines of SiII $\lambda$1260, OI+SiII $\lambda$1303, and CII $\lambda$1334 (mean rest-frame equivalent widths of them are $-1.2 \sim -5.1$\AA). These properties are significantly different from those of the mean rest-frame UV spectrum of LBGs at $z\sim3$, but are quite similar to those of subgroups of LBGs at $z\sim3$ with no or weak Lyalpha emission. The weakness of Lyalpha emission and strong low-ionization interstellar metal absorption lines may indicate that these LBGs at $z\sim5$ are chemically evolved to some degree and have a dusty environment. Since the fraction of such LBGs at $z\sim5$ in our sample is larger than that at $z\sim3$, we may witness some sign of evolution of LBGs from $z\sim5$ to $z\sim3$, though the present sample size is very small. It is also possible, however, that the brighter LBGs tend to show no or weak Lyalpha emission, because our spectroscopic sample is bright (brighter than $L^{\ast}$) among LBGs at $z\sim5$. More observations are required to establish spectroscopic nature of LBGs at $z\sim5$.Comment: 16 pages, 3 figures, accepted by Ap

A Case of Pill-Induced Esophagitis With Mucosal Dissection

With the advance of gastrointestinal endoscopy, pill-induced esophagitis has been detected more frequently, but the association of mucosal dissection is rare. We reported a case of pill-induced esophagitis associated with mucosal dissection

Rhophilin, a small GTPase Rho-binding protein, is abundantly expressed in the mouse testis and localized in the principal piece of the sperm tail

AbstractTissue distribution and cellular localization of rhophilin, a 71 kDa Rho-binding protein, were examined in mice. Rhophilin mRNA was highly expressed in adult testis, but was absent in the testis of W/WV mice deficient in germ cells. An anti-rhophilin antibody detected a band of an expected size in sperm extracts, which was enriched in the tail fraction. Immunofluorescence analysis revealed two lines of striated staining running in parallel in the principal piece of the sperm tail. These results suggest that rhophilin is expressed in germ cells and localized in the fibrous sheath of the sperm tail

Capsaicin, a TRPV1 Ligand, Suppresses Bone Resorption by Inhibiting the Prostaglandin E Production of Osteoblasts, and Attenuates the Inflammatory Bone Loss Induced by Lipopolysaccharide

Capsaicin, a transient receptor potential vanilloid type 1 (TRPV1) ligand, regulates nerve-related pain-sensitive signals, inflammation, and cancer growth. Capsaicin suppresses interleukin-1-induced osteoclast differentiation, but its roles in bone tissues and bone diseases are not known. This study examined the effects of capsaicin on inflammatory bone resorption and prostaglandin E (PGE) production induced by lipopolysaccharide (LPS) in vitro and on bone mass in LPS-treated mice in vivo. Capsaicin suppressed osteoclast formation, bone resorption, and PGE production induced by LPS in vitro. Capsaicin suppressed the expression of cyclooxygenase-2 (COX-2) and membrane-bound PGE synthase-1 (mPGES-1) mRNAs and PGE production induced by LPS in osteoblasts. Capsaicin may suppress PGE production by inhibiting the expression of COX-2 and mPGES-1 in osteoblasts and LPS-induced bone resorption by TRPV1 signals because osteoblasts express TRPV1. LPS treatment markedly induced bone loss in the femur in mice, and capsaicin significantly restored the inflammatory bone loss induced by LPS in mice. TRPV1 ligands like capsaicin may therefore be potentially useful as clinical drugs targeting bone diseases associated with inflammatory bone resorption

Clinical usefulness of the attention-deficit hyperactivity disorder rating scale-IV in the treatment of enuretic children undiagnosed with developmental disorders

To determine the association between attention-deficit hyperactivity disorder （ADHD） and nocturnal enuresis （NE） and its relation to the effectiveness of NE treatment in children undiagnosed with developmental disorders. A total of 154 children with NE （112 males and 42 females） were included in this study, aged ≥5–＜15 years, presenting at the Department of Pediatrics, Showa University Fujigaoka Hospital, between January 2016 and June 2017. None of the participants was diagnosed with developmental disorders. We retrospectively evaluated Attention-Deficit Hyperactivity Disorder Rating Scale-IV （ADHD-RS-IV） scores, Dysfunctional Voiding Symptom Score （DVSS）, NE clinical characteristics, and efficacy of NE treatment. The mean age was 8.0±2.0 years （standard deviation）. Sixty-seven （40.3％） patients presented with daytime incontinence （DI）. The mean total ADHD-RS and DVSS scores were 7.7±8.0 and 6.6±4.3, respectively, and they were significantly correlated （p＝0.049）. ADHD-RS scores were significantly higher in patients with DI than in those without DI （p＝0.0006）. ADHD-RS scores and large-volume DI （a DVSS subscale item） were significantly correlated. Six months after treatment initiation, patients with ＜50％ improvement （nonresponder） in NE had significantly higher total ADHD-RS scores than those with ≥50％ improvement （responder） （p＝0.007）. Even in patients not diagnosed with developmental disorders, ADHD characteristics may influence the clinical course of NE. Evaluation of ADHD characteristics using a screening tool such as the ADHD-RS is important in the NE treatment

Migraine triggers in Asian countries: a narrative review

BackgroundMigraine is one of the most common neurological disorders worldwide. Clinical characteristics of migraine may be somewhat different across ethnic groups. Although factors such as stress, lack of sleep, and fasting are known as migraine triggers, the discussion about geographical differences of migraine triggers in Asia is lacking.MethodsIn this study, we performed a narrative review on migraine triggers in Asia. We searched PubMed for relevant papers published between January 2000 and February 2022.ResultsForty-two papers from 13 Asian countries were included. Stress and sleep are the most frequently reported migraine triggers in Asia. There were some differences in migraine triggers in Asian countries: fatigue and weather common in Eastern Asia and fasting common in Western Asia.ConclusionMajority of the common triggers reported by patients with migraine in Asia were stress and sleep, similar to those reported globally, thus showing they are universally important. Some triggers linked to internal homeostasis are influenced by culture (e.g., alcohol, food/eating habit), and triggers related to environmental homeostasis, such as weather, are highly heterogenous between regions

Generating Vegfr3 reporter transgenic mouse expressing membrane-tagged Venus for visualization of VEGFR3 expression in vascular and lymphatic endothelial cells

Vascular endothelial growth factor receptor 3 (Vegfr3) has been widely used as a marker for lymphatic and vascular endothelial cells during mouse embryonic development and in adult mouse, making it valuable for studying angiogenesis and lymphangiogenesis under normal and pathological conditions. Here, we report the generation of a novel transgenic (Tg) mouse that expresses a membrane-localized fluorescent reporter protein, Gap43-Venus, under the control of the Vegfr3 regulatory sequence. Vegfr3-Gap43-Venus BAC Tg recapitulated endogenous Vegfr3 expression in vascular and lymphatic endothelial cells during embryonic development and tumor development. Thus, this Tg mouse line contributes a valuable model to study angiogenesis and lymphangiogenesis in physiological and pathological contexts

Aging of the Vascular System and Neural Diseases.

Vertebrates have acquired complex high-order functions facilitated by the dispersion of vascular and neural networks to every corner of the body. Blood vessels deliver oxygen and nutrients to all cells and provide essential transport systems for removing waste products. For these functions, tissue vascularization must be spatiotemporally appropriate. Recent studies revealed that blood vessels create a tissue-specific niche, thus attracting attention as biologically active sites for tissue development. Each capillary network is critical for maintaining proper brain function because age-related and disease-related impairment of cognitive function is associated with the loss or diminishment of brain capillaries. This review article highlights how structural and functional alterations in the brain vessels may change with age and neurogenerative diseases. Capillaries are also responsible for filtering toxic byproducts, providing an appropriate vascular environment for neuronal function. Accumulation of amyloid β is a key event in Alzheimer’s disease pathogenesis. Recent studies have focused on associations reported between Alzheimer’s disease and vascular aging. Furthermore, the glymphatic system and meningeal lymphatic systems contribute to a functional unit for clearance of amyloid β from the brain from the central nervous system into the cervical lymph nodes. This review article will also focus on recent advances in stem cell therapies that aim at repopulation or regeneration of a degenerating vascular system for neural diseases