The Circadian Clock as an Essential Molecular Link Between Host Physiology and Microorganisms

Advances in high-throughput sequencing technologies in the past decade has led to a tremendous growth in knowledge about the role played by microorganisms on our body health. Trillions of microbes live in close symbiosis with their host, and have impacts on various aspects of host physiology as well as predisposition to disease. This is a consequence of the direct interaction between host cells and microbes or their signaling molecules, such as metabolites, which can reach and exert their effects in distal tissues. Among the essential factors modulating the human body's ecosystem of symbionts, the circadian clock might be one of the key regulators. The endogenous clock is a highly conserved timekeeper able to align organismal physiology to the daily cycle, thus maximizing survival and fitness. Circadian rhythms coordinate whole-body biological processes synchronizing cellular biochemical reactions, tissue function and finally controlling systemic homeostasis. Intriguingly, growing body of evidence has demonstrated that the host circadian cycle governs the structure of the gut microbiota community and its diurnal rhythmicity, whereas the microbes contribute to maintenance of clock function. In this review, we will give an overview of the multisystem aspects of microbiome-host interactions in the context of circadian rhythmicity. In particular, the effect of the interaction clock-microbial communities on immune system function and metabolic homeostasis will be discussed. Finally, the possible implication of daily rhythm on the gut-microbiome-brain axis will be analyzed, focusing on the reciprocal effects of clock disruption and microbiota alterations on brain function and behavior

Proteinuria screening for children

Proteinuria screening for children.BackgroundIn Japan, urine screenings are performed annually at school for proteinuria and hematuria, but the effectiveness of this practice has not been clarified.MethodsUrine screening at school was performed, and we investigated the prevalence of urine abnormalities and incidence and the causes of their diseases. Therefore, we studied effectiveness of the school-screening program.ResultsThe prevalence of urinary abnormalities was 0.52% among elementary school children and 0.75% among junior high school children. The incidence was 0.24% among elementary school children. The school-screening program is effective in early detection of glomerulonephritis, so the number of new end-stage renal disease (ESRD) patients starting treatment has been changing.DiscussionThe school-screening program is effective for early detection of glomerulonephritis. In case of generations who underwent the school-screening program, the age that one develops ESRD has been rising year by year, and the number of new ESRD patients starting treatment before 20 years old is lower in Japan than in America.ConclusionThe school-screening program in Japan represents a highly effective mass screening technique

The occurrence of neurons with strongly negatively charged surface coats in mammalian, avian, reptilian, amphibian and piscine brains.

Neurons with strongly negatively charged surface coats were recognized in mammalian, avian, reptilian, amphibian and piscine brains. Many large-sized neurons had strongly negatively charged surface coats in the visual cortex and brain stem of the cow, cat, guinea pig, mouse, quail and parakeet. Such neurons were also seen in the brain stem of the lower vertebrates such as the house lizard, Japanese terrapin, bullfrog, newt, carp and sweetfish.</p

Perineuronal Sulfated Proteoglycans in the Adult Rat Brain: Histochemical and Electron Microscopic Studies

Neurons of cerebellar nuclei in the rat brain had a marked surface coat which was stained with cationic iron colloid or aldehyde fuchsin. Neurons with a similar surface coat were also noted in the retrosplenial cortex. The surface coat was stained doubly with cationic iron colloid and aldehyde fuchsin. Digestion with hyaluronidase eliminated the stainability of the surface coat to both agents. Combined digestion with chondroitinase ABC, heparitinase and keratanase eliminated the cationic iron colloid staining but did not interfere with the aldehyde fuchsin staining. Electron microscopy of ultrathin sections revealed that the iron particles were deposited in the perineuronal tissue spaces. These findings indicate that the surface coat consists of sulfated proteoglycans which occupy, as the extracellular matrix, the perineuronal tissue spaces. Many neurons in the retrosplenial cortex were labeled with lectin Vicia villosa agglutinin. Double staining revealed that these lectin-labeled neurons are usually reactive to cationic iron colloid. Few neurons in the cerebellar nuclei were labeled with lectin V. villosa agglutinin.</p

Perineuronal Sulfated Proteoglycans, Cell Surface Glycoproteins and Dark Neurons in the Cingulate Cortex of Newborn and Adult Rats

Many neurons in the adult rat cingulate cortex possess perineuronal sulfated proteoglycans detectable with cationic iron colloid and aldehyde fuchsin, or cell surface glycoproteins reactive to lectin Vicia villosa or soybean agglutinin. The perineuronal sulfated proteoglycans develop three to four weeks after birth. The cell surface glycoproteins develop at earlier stage or two to three weeks after birth. Dark or active neurons begin to appear three to four weeks after birth. These findings indicate that the brain matures after birth or during weaning period.</p

The effect of cyclic phosphatidic acid on the proliferation and differentiation of mouse cerebellar granule precursor cells during cerebellar development

AbstractThe proliferation and differentiation of cerebellar granule cell precursors (GCPs) are highly regulated spatiotemporally during development. We focused on cyclic phosphatidic acid (cPA) as a lipid mediator with a cyclic phosphate group as a regulatory factor of GCPs. While its structure is similar to that of lysophosphatidic acid (LPA), its function is very unique. cPA is known to be present in the cerebellum at high levels, but its function has not been fully elucidated. In this study, we examined the role of cPA on the proliferation and differentiation of GCPs. A cell cycle analysis of GCPs revealed that cPA reduced the number of phospho-histone H3 (Phh3)-positive cells and bromodeoxy uridine (BrdU)-incorporated cells and increased an index of the cell cycle exit. We next analyzed the effect of cPA on GCP differentiation using Tuj1 as a neuronal marker of final differentiation. The results show that cPA increased the number of Tuj1-positive cells. Further analysis of the proliferation of GCPs showed that cPA suppressed Sonic hedgehog (Shh)-dependent proliferation, but did not suppress insulin-like growth factor-1 (IGF-1)-dependent proliferation. P2Y5 (LPA6), an LPA receptor, is highly expressed in GCPs. The knockdown of P2Y5 suppressed the inhibitory effect of cPA on the proliferation of GCPs, suggesting that P2Y5 is a candidate receptor for cPA. Thus, cPA suppresses the Shh-dependent proliferation of GCPs and promotes the differentiation of GCPs through P2Y5. These results demonstrate that cPA plays a critical role in the development of GCPs

Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts

AbstractCyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator and an analog of the growth factor-like phospholipid lysophosphatidic acid (LPA). cPA has a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We showed before that a metabolically stabilized cPA derivative, 2-carba-cPA, relieved osteoarthritis pathogenesis in vivo and induced hyaluronic acid synthesis in human osteoarthritis synoviocytes in vitro. This study focused on hyaluronic acid synthesis in human fibroblasts, which retain moisture and maintain health in the dermis. We investigated the effects of cPA and LPA on hyaluronic acid synthesis in human fibroblasts (NB1RGB cells). Using particle exclusion and enzyme-linked immunosorbent assays, we found that both cPA and LPA dose-dependently induced hyaluronic acid synthesis. We revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA and LPA treatment time dependently. We then characterized the signaling pathways up-regulating hyaluronic acid synthesis mediated by cPA and LPA in NB1RGB cells. Pharmacological inhibition and reporter gene assays revealed that the activation of the LPA receptor LPAR1, Gi/o protein, phosphatidylinositol-3 kinase (PI3K), extracellular-signal-regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding protein (CREB) but not nuclear factor κB induced hyaluronic acid synthesis by the treatment with cPA and LPA in NB1RGB cells. These results demonstrate for the first time that cPA and LPA induce hyaluronic acid synthesis in human skin fibroblasts mainly through the activation of LPAR1-Gi/o followed by the PI3K, ERK, and CREB signaling pathway

Peculiar Distribution of Tumorous Xanthomas in an Adult Case of Erdheim-Chester Disease Complicated by Atopic Dermatitis

Erdheim-Chester disease is a rare non-Langerhans form of histiocytosis with multiple organ involvement. Approximately 20% of patients have xanthoma-like lesions, usually on the eyelids. We report a case of Erdheim-Chester disease in a 32-year-old male who showed peculiar xanthomatous skin lesions and also had atopic dermatitis. His skin manifestations included ring-like yellowish tumors on his periorbital regions, rope necklace-like tumors on his neck, and spindle-shaped tumors on his right preauricular region and cubital fossas. He also had exophthalmos and diabetes insipidus. Chronic eczematous lesions were present on the flexor aspect of his extremities, and his serum eosinophil numbers and immunoglobulin E levels were elevated. A histological examination of his right neck tumor showed foamy macrophages and touton-type giant cells, which were positive for CD68 and CD163 and negative for S-100 and CD1a. We suggest that the complication of atopic dermatitis may have contributed to the uncommon clinical features in this case

解剖体において両側性の星状神経節ブロックは頻繁に硬膜外腔への薬液浸潤を起こす

It is well known that epidural infusion of injectate in association with a C6 paratracheal stellate ganglion block (SGB) leads to negative and/or positive side effects for the patient. However, this associated infusion has not been demonstrated experimentally using cadavers. We found that, in postmortem-fixed cadavers, epidural infusion occurred much more frequently in cases of bilateral SGB than in unilateral SGB. The frequency in the bilateral case (36.1%) was far beyond the two times of the unilateral one (7.7%). The injectate (latex resin, 10 ml for one side) was delivered from the prevertebral deposit into the epidural space by way of the spaces around the C8 and/or T1 spinal nerve roots. Thus, the latex spread around and/or in the brachial plexus usually combined with the epidural infusion. We speculate that the amount of injectate spreading into the prevertebral space in the bilateral injection (total 20 ml) was beyond the hypothetical tentative capacity and that the excess amount made the addional, perineural spread. The present results suggests that, in clinical cases, the frequency of epidural infusion depends on the amount of injectate even in the routine unilateral SGB. However, the cadaveric study did not indicate how much amount is the excess for the living patient