Regulation of Inwardly Rectifying K Channels in Retinal Pigment Epithelial Cells by Intracellular pH

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66255/1/jphysiol.2003.042341.pd

Tumor cell invasion of model 3‐dimensional matrices: demonstration of migratory pathways, collagen disruption, and intercellular cooperation

We report a novel 3‐dimensional model for visualizing tumor cell migration across a nylon mesh‐supported gelatin matrix. To visualize migration across these model barriers, cell proteolytic activity of the pericellular matrix was detected using Bodipy‐BSA (fluorescent upon proteolysis) and DQ™ collagen (fluorescent upon collagenase activity). For 3‐dimensional image reconstruction, multiple optical images at sequential z axis positions were deconvoluted by computer analysis. Specificity was indicated using well‐known inhibitors. Using these fluorescent proteolysis markers and imaging methods, we have directly demonstrated proteolytic and collagenolytic activity during tumor cell invasion. Moreover, it is possible to visualize migratory pathways followed by tumor cells during matrix invasion. Using cells of differing invasive potentials (uPAR‐negative T‐47D wild‐type and uPAR‐positive T‐47D A2–1 cells), we show that the presence of the T‐47D‐A2–1 cells facilitates the entry of T‐47D wild‐type cells into the matrix. In some cases, wild‐type cells follow T‐47D A2–1 cells into the matrix whereas other T‐47D‐wild‐type cells appear to enter without the direct intervention of T‐47D A2–1 cells. Thus, we have developed a new 3‐dimensional model of tumor cell invasion, demonstrated protein and collagen disruption, mapped the pathways followed by tumor cells during migration through an extracellular matrix, and illustrated cross‐talk among tumor cell populations during invasion.—Horino, K., Kindezelskii, A. L., Elner, V. M., Hughes, B. A., Petty, H. R. Tumor cell invasion of model 3‐dimensional matrices: demonstration of migratory pathways, collagen disruption, and intercellular cooperation. FASEB J. 15, 932–939 (2001)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154275/1/fsb2fj000392com.pd

Quantum dynamics of hydrogen atoms on graphene. II. Sticking

Following our recent system-bath modeling of the interaction between a hydrogen atom and a graphene surface [Bonfanti et al., J. Chem. Phys. 143, 124703 (2015)], we present the results of converged quantum scattering calculations on the activated sticking dynamics. The focus of this study is the collinear scattering on a surface at zero temperature, which is treated with high-dimensional wavepacket propagations with the multi-configuration time-dependent Hartree method. At low collision energies, barrier-crossing dominates the sticking and any projectile that overcomes the barrier gets trapped in the chemisorption well. However, at high collision energies, energy transfer to the surface is a limiting factor, and fast H atoms hardly dissipate their excess energy and stick on the surface. As a consequence, the sticking coefficient is maximum ( 3c0.65) at an energy which is about one and half larger than the barrier height. Comparison of the results with classical and quasi-classical calculations shows that quantum fluctuations of the lattice play a primary role in the dynamics. A simple impulsive model describing the collision of a classical projectile with a quantum surface is developed which reproduces the quantum results remarkably well for all but the lowest energies, thereby capturing the essential physics of the activated sticking dynamics investigated

Factors Associated with 5-Year Glaucomatous Progression in Glaucoma Suspect Eyes

Background: The US Preventive Services Task Force found that treatment of early asymptomatic primary open-angle glaucoma reduces visual field defects. However, it remains unclear which factors are associated with glaucomatous progression and which patients are at higher risk. The purpose of this study was to assess demographic factors, medical comorbidities, Humphrey visual field (VF) results, and Cirrus optical coherence tomography variables that could be predictive for 5-year glaucoma progression. Methods: A retrospective longitudinal study was conducted with the following inclusion criteria: glaucoma suspect eyes (defined as an asymmetric cup to disc ratio or an intraocular pressure \u3e21mmHg), best-corrected visual acuity 20/100 or better, spherical equivalent better than −8 diopters and astigmatism less than 3 diopters. Two consecutive abnormal VF tests during a 5-year follow-up was considered glaucomatous progression. Results: A total of 365 eyes (288 patients) were included in the study, of which 55 (15%) converted to glaucoma after 5 years. Logistic regression analysis showed that baseline mean deviation (MD), pattern standard deviation (PSD), VF index, and retinal nerve fiber layer (RNFL) colors were statistically significant in predicting 5-year glaucomatous progression. Though there were differences in glaucoma progression rates when analyzing sex, age, hypertension, diabetes mellitus, family history of glaucoma, and baseline intraocular pressure, these factors were not statistically significant. Conclusions: The study found that VF test results (MD and PSD) and RNFL colors can strongly predict which patients are at an increased risk of glaucoma progression. Clinicians can consider these factors when initiating, or continuing, prophylactic treatment for patients with glaucoma suspect eyes

Toll-Like Receptor 4 (TLR4) of Retinal Pigment Epithelial Cells Participates in Transmembrane Signaling in Response to Photoreceptor Outer Segments

Retinal pigment epithelial (RPE) cells mediate the recognition and clearance of effete photoreceptor outer segments (POS), a process central to the maintenance of normal vision. Given the emerging importance of Toll-like receptors (TLRs) in transmembrane signaling in response to invading pathogens as well as endogenous substances, we hypothesized that TLRs are associated with RPE cell management of POS. TLR4 clusters on human RPE cells in response to human, but not bovine, POS. However, TLR4 clustering could be inhibited by saturating concentrations of an inhibitory anti-TLR4 mAb. Furthermore, human POS binding to human RPE cells elicited transmembrane metabolic and calcium signals within RPE cells, which could be blocked by saturating doses of an inhibitory anti-TLR4 mAb. However, the heterologous combination of bovine POS and human RPE did not trigger these signals. The pattern recognition receptor CD36 collected at the POS–RPE cell interface for both homologous and heterologous samples, but human TLR4 only collected at the human POS–human RPE cell interface. Kinetic experiments of human POS binding to human RPE cells revealed that CD36 arrives at the POS–RPE interface followed by TLR4 accumulation within 2 min. Metabolic and calcium signals immediately follow. Similarly, the production of reactive oxygen metabolites (ROMs) was observed for the homologous human system, but not the heterologous bovine POS–human RPE cell system. As (a) the bovine POS/human RPE combination did not elicit TLR4 accumulation, RPE signaling, or ROM release, (b) TLR4 arrives at the POS–RPE cell interface just before signaling, (c) TLR4 blockade with an inhibitory anti-TLR4 mAb inhibited TLR4 clustering, signaling, and ROM release in the human POS–human RPE system, and (d) TLR4 demonstrates similar clustering and signaling responses to POS in confluent RPE monolayers, we suggest that TLR4 of RPE cells participates in transmembrane signaling events that contribute to the management of human POS

Preliminary Investigation into the Expression of Proton-Coupled Oligopeptide Transporters in Neural Retina and Retinal Pigment Epithelium (RPE): Lack of Functional Activity in RPE Plasma Membranes

Purpose . To determine the expression and functional activity of proton-coupled oligopeptide transporters (POT) in retinal pigment epithelial (RPE) cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41501/1/11095_2004_Article_471009.pd

Factors Associated With 5-Year Glaucomatous Progression In Glaucoma Suspect Eyes: A Retrospective Longitudinal Study

Purpose: To study the association of 5-year glaucomatous progression with several demographic, clinical, visual field and optical coherence tomography (OCT) variables in glaucoma suspect eyes. Methods: A retrospective chart review of 365 eyes of 288 patients were included (323 eyes with suspicious cup-to-disc ratio and 42 eyes with ocular hypertension). The study subjects were divided into two groups: eyes that progressed to glaucoma and those that did not. We calculated the percentage of glaucoma suspect eyes that progressed to glaucoma within 5 years. The inclusion criteria were glaucoma suspect eyes (i.e., suspicious cup-to-disc ratio and/or intraocular pressure \u3e21 mm Hg), age ≥ 30 years old, follow-up time of 5 years, best-corrected visual acuity 20/100 or better, spherical equivalent better than −8 diopters and astigmatism less than 3 diopters. We excluded eyes with any significant retinal or neurological disease, and glaucoma which was determined by at least 2 consecutive reliable visual field tests regardless of the appearance of the optic disc. Results: Bivariate analysis showed eyes that progressed to glaucoma had significantly worse mean deviation, higher pattern standard deviation (PSD), less visual field index, thinner average, superior, and inferior retinal nerve fiber layer thickness (RNFL), and more severe average, superior, and inferior RNFL damages (i.e., color grading scale) at baseline. Logistic regression analysis showed only PSD and severe inferior RNFL damage (i.e., red color) were significantly associated with 5-year glaucomatous progression. Conclusions: Segmental RNFL damage and PSD are associated with 5-year glaucomatous progression in glaucoma suspect eyes

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30