Developing quantitative analysis program of blood flow velocity according to vessel diameter for neovascular age-related macular degeneration using OCTA-VISTA.

This study aimed to develop a quantitative analysis program of blood flow velocity by vessel diameter in neovascular age-related macular degeneration (nAMD) subjects using high-speed swept-source optical coherence tomography angiography. This retrospective, observational, cross-sectional study included 10 eyes of healthy volunteers and 4 eyes of patients with representative nAMD. Novel scan patterns and variable interscan time analysis were utilized to measure the flow parameter, a surrogate marker of blood flow velocity, by vessel diameter within different depths. Detected vessels at superficial and deep as well as outer retinal regions were categorized into three vessel diameters (major vessels (> 40 µm), medium vessels (20-40 µm), and capillaries (< 20 µm)). The flow parameter increased with enlarged vessel diameter in all participants at superficial and deep layer. All nAMD subjects, except for type 3 macular neovascularization (MNV), contained a structure dominated by medium vessels at outer retinal region. The mean flow parameter at outer retinal region was type 1 MNV (1.46 ms-1), type 1 + 2 MNV (0.98 ms-1), and polypoidal choroidal vasculopathy, including branching vascular networks (1.46 ms-1). This program provides the possibility to extract the blood flow information at different depths by vessel diameter types, which is considered to be useful tool for evaluating nAMD pathology and activity.

Anisotropic Photodetachment of Positronium Negative Ions with Linearly Polarized Light.

We report on the anisotropic photodetachment of positronium negative ions, followed by the dissociation into p-wave electrons and positronium atoms, with a linearly polarized laser beam. We have observed a strong recoil effect of the photoelectrons on the translation momentum of the dissociated positronium atoms. With polarization angle-resolved measurements, the asymmetry parameter of the photoemission angular distribution of the ions at a photon energy of 1.165 eV was determined to be 1.97±0.04(stat)±0.07(syst), in agreement with a theoretical prediction. The present method can be applied to explore the unrevealed dissociation dynamics of exotic particle systems and their manipulation with polarized light.

Possible role of p38 MAPK-MNK1-EMI2 cascade in metaphase-II arrest of mouse oocytes.

The Mos-MAPK signaling pathway involving the Mos-MEK1/2-ERK1/2-RSK1/2/3 or MSK1-EMI2 cascade is directly linked to metaphase-II arrest of vertebrate oocytes. In this study, we examined whether p38, a member of the MAPK subfamily, is regulated under the control of Mos and contributes to metaphase-II arrest in the mouse oocyte. Morpholino oligonucleotide-mediated depletion of Mos revealed a remarkable decrease in phosphorylation of p38. Simultaneous treatment of oocytes with two chemical inhibitors of p38 and MEK1/2 induced both release from metaphase II and degradation of cyclin B1, whereas the treatment with each of these two inhibitors had little effect. Moreover, phosphorylation of EMI2 was dramatically abolished by addition of the two inhibitors. Indeed, MNK1, a kinase downstream of p38, exhibited the ability to phosphorylate EMI2. These results suggest that in addition to the Mos-MEK1/2 pathway, the Mos-mediated p38 pathway may be implicated in metaphase-II arrest.

Snail promotes Cyr61 secretion to prime collective cell migration and form invasive tumor nests in squamous cell carcinoma.

We previously identified genes associated with Snail-mediated squamous cell carcinoma (SCC) invasiveness, in which we observed significant elevation of Cyr61 expression. In this study, SCC cell lines overexpressing Cyr61 exhibited constitutive activation of Rho A and upregulated invasiveness without the disruption of homophilic cell attachment. Humoral Cyr61 enhanced further production of endogenous Cyr61 by SCC cells, which stimulated collective cell migration and the development of an invasive tumor nest. We propose a Cyr61-dependent model for the development of invasive SCC nest, whereby a subset of tumor cells that highly produce Cyr61 may direct other tumor cells to undergo collective cell migration, resulting in a formation of primary SCC mass.

PGE2 targets squamous cell carcinoma cell with the activated epidermal growth factor receptor family for survival against 5-fluorouracil through NR4A2 induction.

We found a linear correlation between the Prostaglandin E(2) (PGE(2)) amount and the NR4A2 expression in oral squamous cell carcinoma (SCC) tissues through a statistical analysis among 41 clinical cases. In SCC cell lines, PGE(2) receptor (EP) ligation by exogenous PGE(2) promoted the NR4A2 expression in the cAMP/protein kinase A (PKA)-dependent manner. The process required a nature of SCC cell represented by constitutive activated epidermal growth factor receptor (EGFR) family. Targeted inactivation of the EGFRs interfered the PGE(2)-dependent NR4A2 expression. The PGE(2)-dependent NR4A2 induction is essential for the resistance to anti-cancer drug-induced apoptosis especially in SCC cells which showed constitutive EGFRs activity via autocrine epiregulin, a ligand for EGFRs. Conversely, SCC cells which lack epiregulin expression in their nature could gain the ability to promote the NR4A2 expression in response to PGE(2) and attain the resistance to anti-cancer drug-induced apoptosis under the existence of exogenous epiregulin. These findings suggest that susceptibility of SCC to anti-cancer drug could be compromised when PGE(2) was delivered in the microenvironment of SCC cells supported by constitutive EGFR family activities as their nature.

Oxazaborolidinone-catalyzed enantioselective Friedel-Crafts alkylation of furans and indoles with alpha,beta-unsaturated ketones.

allo-Threonine-derived oxazaborolidinone (10 mol %) catalyzes the Friedel-Crafts alkylation of furans and indoles with simple acyclic alpha,beta-unsaturated ketones to give products with high yield and high enantioselectivity. The use of N,N-dimethylaniline (2.5-10 mol %) as an additive is essential for enantioselectivity.

Oxazaborolidinone-catalyzed enantioselective Diels-Alder reaction of acyclic alpha,beta-unsaturated ketones.

allo-Threonine-derived O-acyl-B-phenyl-oxazaborolidinones are demonstrated to be powerful and highly enantioselective Lewis acid catalysts for the Diels-Alder reaction of simple acyclic enone dienophiles, expanding the scope of ketone dienophiles and dienes. With 10 to 20 mol % of catalyst, the Diels-Alder adducts are obtained in 76-98% ee with high endo-selectivity. The catalyst exhibits high activity for the reaction with the less reactive beta-substituted dienophiles and the less reactive 1,3-cycohexadiene and 1,3-butadiene derivatives. The application of the catalysts to the Diels-Alder reaction of furan is also described.

Appearance of the oocyte activation of mouse round spermatids cultured in vitro.

This study was undertaken to determine the expression time of fertilization and oocytes activation abilities of spermatids in the mouse. When elongating or elongated spermatids isolated from fresh testes of adult males (B6D2F1) were injected into mature mouse oocytes, both spermatids could activate the mature oocytes and occur fertilization. On the one hand, the round spermatids could not activate mature oocytes, when microinjected into oocytes. In some experiments, recovered round spermatids were cultured under co-culture systems using Sertoli cells as a feeder cell. Under the co-culture system, developed elongating spermatids could stimulate and fertilized mature oocytes. These results indicate that the start of oocyte activation appearance is between the stage of round spermatid and elongating spermatids and the activation ability increases with the advance of spermiogensis. On the other hand, round spermatids isolated from males of ICR strain mouse already have the oocyte activation ability and the fertilizing ability. The result obtained suggests that the expression time of the oocyte activating ability is difficult between the mouse strain.

Myelin transcription factor 1 (MyT1) immunoreactivity in infants with periventricular leukomalacia.

Myelin transcription factor 1 (MyT1) is a zinc-dependent, DNA-binding protein, and is known to be expressed in early progenitors of oligodendrocytes. We examined the immunoreactivity of MyT1 in developing human brains and brains with periventricular leukomalacia (PVL) to understand the relationship between the expression of MyT1 and myelination in PVL brains. MyT1-positive glial cells were first detected at 19 gestational weeks (GWs) and then gradually increased until 26-29 GWs in the control group. Then they decreased and became very rare at 1 year of age. The expression of MyT1 immunoreactivity shifted from the nucleus to the cytoplasm of the glial cells in the developmental time course. In the chronic stage of PVL, MyT1-positive cells were significantly increased around necrotic foci and some of the regions were coincident with increasing MBP and PLP immunoreactivity. These results may reflect myelin repair on dysmyelination around PVL areas. Therefore, MyT1 may play an important role in the myelin repair in PVL regions.