Gene expression changes within Müller glial cells in retinitis pigmentosa

Purpose: Retinitis pigmentosa (RP) is a progressive retinal degeneration in which the retina loses nearly all of its photoreceptor cells and undergoes major structural changes. Little is known regarding the role the resident glia, the Müller glia, play in the progression of the disease. In this article, we define gene expression changes in Müller glial cells (MGCs) from two different mouse models of RP, the retinal degeneration 1 (rd1) and rhodopsin knockout (Rhod-ko) models. The RNA repertoire of single MGCs was comprehensively profiled, and a comparison was made between MGCs from wild-type (WT) and mutant retinas. Two time points were chosen for analysis, one at the peak of rod photoreceptor death and one during the period of cone photoreceptor death. Methods: Retinas were dissociated, and single MGCs were chosen under a dissecting microscope using a micropipette. Single cell cDNAs were generated and genome-wide profiles were obtained by hybridization to Affymetrix arrays. A comparison was made among all samples to discover the changes in gene expression during the periods of rod and cone photoreceptor death. Results: MGCs respond to retinal degeneration by undergoing gliosis, a process marked by the upregulation of glial fibrillary acidic protein (Gfap). Many additional transcripts were found to change. These can be placed into functional clusters, such as retinal remodeling, stress response, and immune-related response. Conclusions: A high degree of heterogeneity among the individual cells was observed, possibly due to their different spatial proximities to dying cells and/or inherent heterogeneity among MGCs

Relativistic calculation of the triton binding energy and its implications

First results for the triton binding energy obtained from the relativistic spectator or Gross equation are reported. The Dirac structure of the nucleons is taken into account. Numerical results are presented for a family of realistic OBE models with off-shell scalar couplings. It is shown that these off-shell couplings improve both the fits to the two-body data and the predictions for the binding energy.Comment: 5 pages, RevTeX 3.0, 1 figure (uses epsfig.sty

The transcriptome of retinal Müller glial cells

Müller glial cells are the major type of glia in the mammalian retina. To identify the molecular machinery that defines Müller glial cell identity and function, single cell gene expression profiling was performed on Affymetrix microarrays. Identification of a cluster of genes expressed at high levels suggests a Müller glia core transcriptome, which likely underlies many of the functions of Müller glia. Expression of components of the cell cycle machinery and the Notch pathway, as well as of growth factors, chemokines, and lipoproteins might allow communication between Müller glial cells and the neurons that they support, including modulation of neuronal activity. This approach revealed a set of transcripts that were not previously characterized in (Müller) glia; validation of the expression of some of these genes was performed by in situ hybridization. Genes expressed exclusively by Müller glia were identified as novel markers. In addition, a novel BAC transgenic mouse that expresses Cre in Müller glia cells was generated. The molecular fingerprint of Müller glia provides a foundation for further studies of Müller glia development and function in normal and diseased states

Annealing schedule from population dynamics

We introduce a dynamical annealing schedule for population-based optimization algorithms with mutation. On the basis of a statistical mechanics formulation of the population dynamics, the mutation rate adapts to a value maximizing expected rewards at each time step. Thereby, the mutation rate is eliminated as a free parameter from the algorithm.Comment: 6 pages RevTeX, 4 figures PostScript; to be published in Phys. Rev.

Quantum Monte Carlo Studies of Relativistic Effects in Light Nuclei

Relativistic Hamiltonians are defined as the sum of relativistic one-body kinetic energy, two- and three-body potentials and their boost corrections. In this work we use the variational Monte Carlo method to study two kinds of relativistic effects in the binding energy of 3H and 4He. The first is due to the nonlocalities in the relativistic kinetic energy and relativistic one-pion exchange potential (OPEP), and the second is from boost interaction. The OPEP contribution is reduced by about 15% by the relativistic nonlocality, which may also have significant effects on pion exchange currents. However, almost all of this reduction is canceled by changes in the kinetic energy and other interaction terms, and the total effect of the nonlocalities on the binding energy is very small. The boost interactions, on the other hand, give repulsive contributions of 0.4 (1.9) MeV in 3H (4He) and account for 37% of the phenomenological part of the three-nucleon interaction needed in the nonrelativistic Hamiltonians.Comment: 33 pages, RevTeX, 11 PostScript figures, submitted to Physical Review

Prediction of locally stable RNA secondary structures for genome-wide surveys

Motivation: Recently novel classes of functional RNAs, most prominently the miRNAs have been discovered, strongly suggesting that further types of functional RNAs are still hidden in the recently completed genomic DNA sequences. Only few techniques are known, however, to survey genomes for such RNA genes. When sufficiently similar sequences are not available for comparative approaches the only known remedy is to search directly for structural features. Results: We present here efficient algorithms for computing locally stable RNA structures at genome-wide scales. Both the minimum energy structure and the complete matrix of base pairing probabilities can be computed in (N × L2) time and (N + L2) memory in terms of the length N of the genome and the size L of the largest secondary structure motifs of interest. In practice, the 100 Mb of the complete genome of Caenorhabditis elegans can be folded within about half a day on a modern PC with a search depth of L = 100. This is sufficient example for a survey for miRNAs

Monitoring Ion Channel Function In Real Time Through Quantum Decoherence

In drug discovery research there is a clear and urgent need for non-invasive detection of cell membrane ion channel operation with wide-field capability. Existing techniques are generally invasive, require specialized nano structures, or are only applicable to certain ion channel species. We show that quantum nanotechnology has enormous potential to provide a novel solution to this problem. The nitrogen-vacancy (NV) centre in nano-diamond is currently of great interest as a novel single atom quantum probe for nanoscale processes. However, until now, beyond the use of diamond nanocrystals as fluorescence markers, nothing was known about the quantum behaviour of a NV probe in the complex room temperature extra-cellular environment. For the first time we explore in detail the quantum dynamics of a NV probe in proximity to the ion channel, lipid bilayer and surrounding aqueous environment. Our theoretical results indicate that real-time detection of ion channel operation at millisecond resolution is possible by directly monitoring the quantum decoherence of the NV probe. With the potential to scan and scale-up to an array-based system this conclusion may have wide ranging implications for nanoscale biology and drug discovery.Comment: 7 pages, 6 figure