Intravitreal bevacizumab injection and carotid artery stent replacement for neovascular glaucoma in internal carotid artery occlusion

Neovascular glaucoma (NVG) secondary to internal carotid artery (ICA) occlusion is usually resistant to treatment. We report a case of NVG with ICA occlusion improved by intravitreal bevacizumab (IVB) injection and carotid artery stent replacement (CAS), even though we did not perform panretinal photocoagulation. A 67-year-old male with NVG noted visual loss in his left eye. Magnetic resonance angiography showed left ICA occlusion. He was diagnosed with NVG secondary to ICA occlusion. The next day, we carried out IVB injection in his left eye, following which the iris and angle neovascularization regressed, and the intraocular pressure decreased to normal within a day after the injection. CAS was performed on his left ICA at a month post injection. Two months later, we reinjected bevacizumab in his left eye. His condition remained stable with no recurrence over two years. This case indicates that IVB injection and CAS are useful for early-stage NVG secondary to ICA occlusion

On Ghost Structure of Vacuum Superstring Field Theory

After discussing the general form of the kinetic operator around the tachyon vacuum, we determine the specific form of the pure-ghost kinetic operator Q^ by requiring the twist invariance of the action. We obtain a novel result that the Grassmann-even piece Q_even of Q^ must act differently on GSO(+) sector and on GSO(-) sector to preserve the twist invariance, and show that this structure is crucial for gauge invariance of the action. With this choice of Q^, we construct a solution in an approximation scheme which is conjectured to correspond to a non-BPS D9-brane. We consider both 0-picture cubic and Berkovits' non-polynomial superstring field theories for the NS sector.Comment: 1+42 pages, 5 figures. v2: a reference added, and a brief comment added (footnote 14). v3: version to appear in NPB. Numerical coefficients in front of the kinetic operators, and some signs in the eqs. of motion, have been corrected. Some minor modification

Identification of the matricellular protein Fibulin-5 as a target molecule of glucokinase-mediated calcineurin/NFAT signaling in pancreatic islets

Glucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The islet Fbln5 expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase in Fbln5 expression was diminished in Irs-2-deficient islets. GKA-induced Fbln5 upregulation in the islets was blunted by a glucokinase inhibitor, KATP channel opener, Ca2+ channel blocker and calcineurin inhibitor, while it was augmented by harmine, a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) 1 A inhibitor. Although deletion of Fbln5 in mice had no significant effects on the glucose tolerance or β-cell functions, adenovirus-mediated Fbln5 overexpression increased glucose-stimulated insulin secretion in INS-1 rat insulinoma cells. Since the islet Fbln5 expression is regulated through a glucokinase/KATP channel/calcineurin/nuclear factor of activated T cells (NFAT) pathway crucial for the maintenance of β-cell functions, further investigation of Fbln5 functions in the islets is warranted

DPP-4 inhibition improves early mortality, β cell function, and adipose tissue inflammation in db/db mice fed a diet containing sucrose and linoleic acid

Additional file 3: Figure S2. Liver and epididymal fat weights in db/+ mice and db/db mice. The experiments were performed in db/+ or db/db mice fed an SL diet, SO diet, SL containing DPP-4 inhibitor (0.4% des-fluoro-sitagliptin) diet, or SO containing DPP-4 inhibitor diet for 8 weeks. (left) Liver weights as a proportion of body weight (n = 5). (right) Epididymal fat weights as a proportion of body weight (n = 5)

EBF1 and PAX5 control pro-B cell expansion via opposing regulation of the Myc gene

Genes encoding B lineage restricted transcription factors are frequently mutated in B-lymphoid leukemias, suggesting a close link between normal and malignant B-cell development. One of these transcription factors is Early B cell Factor 1 (EBF1), a protein of critical importance for lineage specification and survival of B-lymphoid progenitors. Here, we report that impaired EBF1 function in mouse B-cell progenitors results in reduced expression of Myc. Ectopic expression of MYC partially rescued B-cell expansion in the absence of EBF1 both in vivo and in vitro. Using chromosome conformation analysis in combination with ATAC-seq, ChIP-seq and reporter gene assays, we identified six EBF responsive enhancer elements within the Myc locus. CRISPR-Cas9 mediated targeting of EBF1 binding sites identified one element of key importance for Myc expression and pro-B cell expansion. These data provide evidence that Myc is a direct target of EBF1. Furthermore, ChIP-seq analysis revealed that several regulatory elements in the Myc locus are targets of PAX5. However, ectopic expression of PAX5 in EBF1 deficient cells inhibits the cell cycle and reduces Myc expression, suggesting that EBF1 and PAX5 act in an opposing manner to regulate Myc levels. This hypothesis is further substantiated by the finding that Pax5 inactivation reduces requirements for EBF1 in pro-B cell expansion. The binding of EBF1 and PAX5 to regulatory elements in the human MYC gene in a B-ALL cell line indicate that the EBF1:PAX5:MYC regulatory loop is conserved and may control both normal and malignant B-cell development

Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis

To understand the developmental trajectories in early lymphocyte differentiation, we identified differentially expressed surface markers on lineage-negative lymphoid progenitors (LPs). Single-cell polymerase chain reaction experiments allowed us to link surface marker expression to that of lineage-associated transcription factors (TFs) and identify GFRA2 and BST1 as markers of early B cells. Functional analyses in vitro and in vivo as well as single-cell gene expression analyses supported that surface expression of these proteins defined distinct subpopulations that include cells from both the classical common LPs (CLPs) and Fraction A compartments. The formation of the GFRA2-expressing stages of development depended on the TF EBF1, critical both for the activation of stage-specific target genes and modulation of the epigenetic landscape. Our data show that consecutive expression of Ly6D, GFRA2, and BST1 defines a developmental trajectory linking the CLP to the CD19(+) progenitor compartment.Peer reviewe

Autonomous assembly and disassembly of gliding molecular robots regulated by a DNA-based molecular controller

自分で集合と散開をする群体分子ロボットを開発--病気の自動的なピンポイント診断と治療への適用に期待--.京都大学プレスリリース. 2024-06-03.In recent years, there has been a growing interest in engineering dynamic and autonomous systems with robotic functionalities using biomolecules. Specifically, the ability of molecular motors to convert chemical energy to mechanical forces and the programmability of DNA are regarded as promising components for these systems. However, current systems rely on the manual addition of external stimuli, limiting the potential for autonomous molecular systems. Here, we show that DNA-based cascade reactions can act as a molecular controller that drives the autonomous assembly and disassembly of DNA-functionalized microtubules propelled by kinesins. The DNA controller is designed to produce two different DNA strands that program the interaction between the microtubules. The gliding microtubules integrated with the controller autonomously assemble to bundle-like structures and disassemble into discrete filaments without external stimuli, which is observable by fluorescence microscopy. We believe this approach to be a starting point toward more autonomous behavior of motor protein–based multicomponent systems with robotic functionalities

Comments on Solutions of Vacuum Superstring Field Theory

We study classical solutions of vacuum version of Berkovits' superstring field theory, focusing on the (super)ghost sector. We first argue that the supersliver state which is annihilated by eta_0, though it has the correct quantum numbers and solves the equation of motion, is actually non-perturbatively pure-gauge, and hence it fails to describe a D-brane. As a step toward the construction of non-trivial solutions, we calculate e^{-Phi}Qe^{Phi} for twisted superslivers. As a by-product, we find that the bc-twisted sliver solution in bosonic VSFT can, at least formally, also be written as a pure-gauge configuration.Comment: 1+21 pages, no figures. v2:Some expressions in eqs.(4.11)-(5.4) have been corrected, with our main conclusions unchange

Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma

Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBVencoded RNA.We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-a, and arginase 1, suggesting the immune regulatory role of BART miRNAs.The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma.These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV1 B-cell lymphoma. (Blood. 2018;131(23):2552-2567)