Insulin-like Growth Factor Binding Protein Expression in Human Retinal Pigment Epithelial Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73426/1/j.1749-6632.1993.tb26229.x.pd

Receptor-Coupled Phosphoinositide Hydrolysis in Human Retinal Pigment Epithelium

Carbachol and histamine stimulated phosphoinositide (PPI) hydrolysis in cultured human retinal pigment epithelium (RPE), as reflected by an accumulation of 3 H-inositol phosphates in the presence of 10 m M Li + . Carbachol increased PPI hydrolysis to greater than 600% of basal with an EC 50 of 60 Μ M ; stimulation was linear up to 60 min. This activation likely occurred via the M 3 muscarinic cholinergic receptor based on the IC 50 values for 4-diphenylacetoxy- N -methylpiperidine methiodide (0.47 n M ), pirenzepine (280 n M ), and 11-[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro-6 H -pyrido[2,3- b ][1,4]benzodiazepin-6-one (1.4 Μ M ). Carbachol-mediated PPI hydrolysis was decreased by 80% in the absence of extracellular Ca 2+ . Histamine stimulated PPI turnover in a linear manner by 180% with an EC 50 of 20 Μ M by the H 1 histaminergic receptor. Serotonin, glutamate, norepinephrine, and dopamine were inactive. In human RPE, the resting cytoplasmic Ca 2+ concentration, as determined by fura-2 fluorescence, was 138 ± 24 n M . On the addition of carbachol, there was a 180% increase in peak intracellular Ca 2+ ; addition of histamine increased intracellular Ca 2+ by 187%. These results suggest receptor-mediated, inositol lipid hydrolysis is coupled to intracellular Ca 2+ flux in human RPE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66430/1/j.1471-4159.1991.tb03471.x.pd

Self-dual noncommutative \phi^4-theory in four dimensions is a non-perturbatively solvable and non-trivial quantum field theory

We study quartic matrix models with partition function Z[E,J]=\int dM \exp(trace(JM-EM^2-(\lambda/4)M^4)). The integral is over the space of Hermitean NxN-matrices, the external matrix E encodes the dynamics, \lambda>0 is a scalar coupling constant and the matrix J is used to generate correlation functions. For E not a multiple of the identity matrix, we prove a universal algebraic recursion formula which gives all higher correlation functions in terms of the 2-point function and the distinct eigenvalues of E. The 2-point function itself satisfies a closed non-linear equation which must be solved case by case for given E. These results imply that if the 2-point function of a quartic matrix model is renormalisable by mass and wavefunction renormalisation, then the entire model is renormalisable and has vanishing \beta-function. As main application we prove that Euclidean \phi^4-quantum field theory on four-dimensional Moyal space with harmonic propagation, taken at its self-duality point and in the infinite volume limit, is exactly solvable and non-trivial. This model is a quartic matrix model, where E has for N->\infty the same spectrum as the Laplace operator in 4 dimensions. Using the theory of singular integral equations of Carleman type we compute (for N->\infty and after renormalisation of E,\lambda) the free energy density (1/volume)\log(Z[E,J]/Z[E,0]) exactly in terms of the solution of a non-linear integral equation. Existence of a solution is proved via the Schauder fixed point theorem. The derivation of the non-linear integral equation relies on an assumption which we verified numerically for coupling constants 0<\lambda\leq (1/\pi).Comment: LaTeX, 64 pages, xypic figures. v4: We prove that recursion formulae and vanishing of \beta-function hold for general quartic matrix models. v3: We add the existence proof for a solution of the non-linear integral equation. A rescaling of matrix indices was necessary. v2: We provide Schwinger-Dyson equations for all correlation functions and prove an algebraic recursion formula for their solutio

Does self-love or self-hate predict conspiracy beliefs? Narcissism, self-esteem, and the endorsement of conspiracy theories

Across three studies, we examined the role of self-evaluation in predicting conspiracy beliefs. Previous research linked the endorsement of conspiracy theories to low self-esteem. We propose that conspiracy theories should rather be appealing to individuals with exaggerated feelings of self-love, such as narcissists, due to their paranoid tendencies. In Study 1, general conspiracist beliefs were predicted by high individual narcissism but low self-esteem. Study 2 demonstrated that these effects were differentially mediated by paranoid thoughts, and independent of the effects of collective narcissism. Individual narcissism predicted generalized conspiracist beliefs, regardless of the conspiracy theories implicating in-group or out-group members, while collective narcissism predicted belief in out-group but not in-group conspiracies. Study 3 replicated the effects of individual narcissism and self-esteem on the endorsement of various specific conspiracy theories and demonstrated that the negative effect of self-esteem was largely accounted for by the general negativity toward humans associated with low self-esteem

Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia

<p>Abstract</p> <p>Background</p> <p>A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described.</p> <p>Methods</p> <p>An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under 16 kg/m²or CD4⁺lymphocyte counts of less than 50 cells/mm³, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality.</p> <p>Results</p> <p>Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p < 0.05 for all comparisons), independent of known risk factors for early ART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not.</p> <p>Conclusions</p> <p>The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.</p

Crossover phenomena in spin models with medium-range interactions and self-avoiding walks with medium-range jumps

We study crossover phenomena in a model of self-avoiding walks with medium-range jumps, that corresponds to the limit $N\to 0$ of an $N$-vector spin system with medium-range interactions. In particular, we consider the critical crossover limit that interpolates between the Gaussian and the Wilson-Fisher fixed point. The corresponding crossover functions are computed using field-theoretical methods and an appropriate mean-field expansion. The critical crossover limit is accurately studied by numerical Monte Carlo simulations, which are much more efficient for walk models than for spin systems. Monte Carlo data are compared with the field-theoretical predictions concerning the critical crossover functions, finding a good agreement. We also verify the predictions for the scaling behavior of the leading nonuniversal corrections. We determine phenomenological parametrizations that are exact in the critical crossover limit, have the correct scaling behavior for the leading correction, and describe the nonuniversal lscrossover behavior of our data for any finite range.Comment: 43 pages, revte

Critical Exponents, Hyperscaling and Universal Amplitude Ratios for Two- and Three-Dimensional Self-Avoiding Walks

We make a high-precision Monte Carlo study of two- and three-dimensional self-avoiding walks (SAWs) of length up to 80000 steps, using the pivot algorithm and the Karp-Luby algorithm. We study the critical exponents $\nu$ and $2\Delta_4 -\gamma$ as well as several universal amplitude ratios; in particular, we make an extremely sensitive test of the hyperscaling relation $d\nu = 2\Delta_4 -\gamma$. In two dimensions, we confirm the predicted exponent $\nu = 3/4$ and the hyperscaling relation; we estimate the universal ratios $\ / \ = 0.14026 \pm 0.00007$, $\ / \ = 0.43961 \pm 0.00034$ and $\Psi^* = 0.66296 \pm 0.00043$ (68\% confidence limits). In three dimensions, we estimate $\nu = 0.5877 \pm 0.0006$ with a correction-to-scaling exponent $\Delta_1 = 0.56 \pm 0.03$ (subjective 68\% confidence limits). This value for $\nu$ agrees excellently with the field-theoretic renormalization-group prediction, but there is some discrepancy for $\Delta_1$. Earlier Monte Carlo estimates of $\nu$, which were $\approx\! 0.592$, are now seen to be biased by corrections to scaling. We estimate the universal ratios $\ / \ = 0.1599 \pm 0.0002$ and $\Psi^* = 0.2471 \pm 0.0003$; since $\Psi^* > 0$, hyperscaling holds. The approach to $\Psi^*$ is from above, contrary to the prediction of the two-parameter renormalization-group theory. We critically reexamine this theory, and explain where the error lies.Comment: 87 pages including 12 figures, 1029558 bytes Postscript (NYU-TH-94/09/01

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P &lt; 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T&gt;C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P &lt; .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies