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Cigarette smoke (CS)-induced accumulation of mitochondrial damage has been widely implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Mitophagy plays a crucial role in eliminating damaged mitochondria, and is governed by the PINK1 (PTEN induced putative protein kinase 1)-PRKN (parkin RBR E3 ubiquitin protein ligase) pathway. Although both increased PINK1 and reduced PRKN have been implicated in COPD pathogenesis in association with mitophagy, there are conflicting reports for the role of mitophagy in COPD progression. To clarify the involvement of PRKN-regulated mitophagy in COPD pathogenesis, prkn knockout (KO) mouse models were used. To illuminate how PINK1 and PRKN regulate mitophagy in relation to CS-induced mitochondrial damage and cellular senescence, overexpression and knockdown experiments were performed in airway epithelial cells (AEC). In comparison to wild-type mice, prkn KO mice demonstrated enhanced airway wall thickening with emphysematous changes following CS exposure. AEC in CS-exposed prkn KO mice showed accumulation of damaged mitochondria and increased oxidative modifications accompanied by accelerated cellular senescence. In vitro experiments showed PRKN overexpression was sufficient to induce mitophagy during CSE exposure even in the setting of reduced PINK1 protein levels, resulting in attenuation of mitochondrial ROS production and cellular senescence. Conversely PINK1 overexpression failed to recover impaired mitophagy caused by PRKN knockdown, indicating that PRKN protein levels can be the rate-limiting factor in PINK1-PRKN-mediated mitophagy during CSE exposure. These results suggest that PRKN levels may play a pivotal role in COPD pathogenesis by regulating mitophagy, suggesting that PRKN induction could mitigate the progression of COPD. Abbreviations: AD: Alzheimer disease; AEC: airway epithelial cells; BALF: bronchoalveolar lavage fluid; AKT: AKT serine/threonine kinase; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; COPD: chronic obstructive pulmonary disease; CS: cigarette smoke; CSE: CS extract; CXCL1: C-X-C motif chemokine ligand 1; CXCL8: C-X-C motif chemokine ligand 8; HBEC: human bronchial epithelial cells; 4-HNE: 4-hydroxynonenal; IL: interleukin; KO: knockout; LF: lung fibroblasts; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; 8-OHdG: 8-hydroxy-2ʹ-deoxyguanosine; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin protein ligase; PCD: programmed cell death; PFD: pirfenidone; PIK3C: phosphatidylinositol-4:5-bisphosphate 3-kinase catalytic subunit; PINK1: PTEN induced putative kinase 1; PTEN: phosphatase and tensin homolog; RA: rheumatoid arthritis; ROS: reactive oxygen species; SA-GLB1/β-Gal: senescence-associated-galactosidase, beta 1; SASP: senescence-associated secretory phenotype; SNP: single nucleotide polymorphism; TNF: tumor necrosis factor. [ABSTRACT FROM AUTHOR]

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF. [ABSTRACT FROM PUBLISHER]

In order to evaluate the effects of settings of digital fisheye photography on estimates of relative illuminance (RI) within a forest under low light conditions, we assessed the effectiveness of some estimators, i.e., canopy openness (CO), sky factor (SF), and diffuse transmittance (DIF). The estimates were calculated from digital hemispherical photographs taken with two different exposure settings, i.e., the reference exposure setting and the auto-exposure setting. We also presented a new estimator (%Exposure), which does not require image analysis, and compared it with other estimators calculated from a digital hemispherical photograph using image analysis. The CO, SF, and DIF calculated from digital hemispherical photographs taken with auto-exposure setting were not significantly correlated with RI. However, those calculated from digital hemispherical photographs taken with reference exposure settings were significantly correlated with RI. On the other hand, %Exposure showed a slightly higher correlation with RI compared with the other estimators. [ABSTRACT FROM AUTHOR]

Brucine inclusion crystals with neutral guest molecules exhibit guest-dependent polymorphism due to a hierarchical structure. Chiral brucine molecules are regarded as a primary structure and assemble to form a chiral tape with a 2 1 axis as a common secondary structure. Such tapes meet together in various modes to constitute different bundles as a tertiary structure. The bundle modes are theoretically classified into eight types, which were screened by alteration of guest compounds in the volume range from 39 to 150 Å 3 . [ABSTRACT FROM AUTHOR]

Conclusions . Postural responses differed according to the stimulus direction, i.e. vertical visual stimulation induced head rather than trunk displacements. Accordingly, it could be that center of foot pressure (COP) responses tended to underestimate the postural sway during visual stimulation. Objectives . To investigate head and body sway in response to vertical visual surround motion, and to examine the correlation between the displacements of head and body segments derived from video-motion analysis and COP measurements. Material and methods . Postural sway was assessed in 10 young female subjects by video-motion analysis of four different head and body segments, and by use of force-plate posturography. Head and body sway in the pitch plane was induced by rotating a random pattern of dots about the subject's inter-aural axis at a constant acceleration of 1°/s 2 or a constant velocity of 60°/s in darkness. Results. Generally, head displacement was greater than that of other body parts during vertical optokinetic stimulation (OKS). In most subjects, maximum head displacements were induced in the same direction as the visual motion. Downward OKS induced a forward head and body sway. The COP trajectory correlated well with the displacements of each head and body segment during downward OKS. In contrast, postural responses to upward OKS were complicated in terms of their time course. The correlation coefficient between each head and body segment and the COP varied among individuals for upward OKS. [ABSTRACT FROM AUTHOR]

Conclusion Our results indicate that the illusion of self-motion is a significant factor leading to spatial disorientation. Objective Under normal circumstances, self-motion is perceived in response to motion of the head and body. However, under certain conditions, such as virtual reality environments, visually induced self-motion can be perceived even though the subject is not actually moving, a phenomenon known as "vection". The aim of this study was to examine the possible influence of illusory self-rotation (circular vection) on postural adjustments. Material and methods The subjects were 10 young females with no history of ocular or vestibular disease. Video-motion analysis was applied to measure postural movements during vertical optokinetic stimulation. Results For most subjects, movement of the visual surroundings induced head and body displacements in the same direction as that of the visual stimulus, regardless of the onset of self-motion perception. However, there was a significant increase in postural instability after the subjects began to perceive false self-motion in the opposite direction to that of the visual stimulus. [ABSTRACT FROM AUTHOR]

In order to estimate the influence of flux on plasma refilling during hemodialysis (HD), prospective crossover studies were performed in 10 HD patients with low-flux and high-flux dialyzers. Hematocrit was continuously monitored to assess changes in blood volume. In addition, plasma osmolarity and total protein concentration were measured. Intradialytic reductions in body weight (-5 ± 1 vs -5 ± 1%) and plasma osmolarity (-5 ± 1 vs -5 ± 1%) were similar in both conditions. Although mean blood pressure remained unchanged in either state, the decrease in blood volume was larger in high-flux HD (-13 ± 2 vs -10 ± 2%, p < 0.05). In spite of greater contraction in blood volume during high-flux HD, total proteins were increased equally between low-flux and high-flux HD (11 ± 4 vs 11 ± 4%). Our data that although high-flux HD failed to induce significant drops in blood pressure, it elicited greater magnitude of decreases in blood volume, implicate the judicious application of high-flux HD. [ABSTRACT FROM AUTHOR]

The detection of intense sound-induced vestibular-evoked myogenic potentials (VEMPs) on the sternocleidomastoid muscle comprises the basis of the saccular function test. In order to evaluate the endolymphatic hydrops (EH) of the saccule of the inner ear, a glycerol VEMP (GVEMP) test was performed in 15 patients with unilateral typical Ménière's disease (UMD) and 7 with delayed endolymphatic hydrops (DEH). Using the GVEMP test, 8 of the 15 patients (53%) with UMD were evaluated as being abnormal. In addition, a greater number of patients (67%) were judged to be abnormal when the results of the GVEMP test were combined with those from a glycerol dehydration test, trans-tympanic electrocochleography (ECochG) or furosemide vestibulo-ocular reflex test (FVOR). Four of the 7 patients with DEH (57%) showed abnormal results in the GVEMP test. In particular, in patients with the ipsilateral type of DEH, only the GVEMP test was able to detect the affected side. These findings suggest that the GVEMP test is a new and useful test for EH, and that a test battery comprising the GVEMP test together with one of the other three tests is useful for diagnosing EH of the inner ear. [ABSTRACT FROM AUTHOR]