Building a glaucoma interaction network using a text mining approach.

Background: The volume of biomedical literature and its underlying knowledge base is rapidly expanding, making it beyond the ability of a single human being to read through all the literature. Several automated methods have been developed to help make sense of this dilemma. The present study reports on the results of a text mining approach to extract gene interactions from the data warehouse of published experimental results which are then used to benchmark an interaction network associated with glaucoma.

Regulatory networks in retinal ischemia-reperfusion injury.

Background: Retinal function is ordered by interactions between transcriptional and posttranscriptional regulators at the molecular level. These regulators include transcription factors (TFs) and posttranscriptional factors such as microRNAs (miRs). Some studies propose that miRs predominantly target the TFs rather than other types of protein coding genes and such studies suggest a possible interconnection of these two regulators in co-regulatory networks.

Ischemia-reperfusion injury of the retina is linked to necroptosis via the ERK1/2-RIP3 pathway.

Purpose: Ischemia-reperfusion (IR) injury is involved in the pathology of many retinal disorders since it contributes to the death of retinal neurons and the subsequent decline in vision. We determined the molecular patterns of some of the principal molecules involved in necroptosis and investigated whether IR retinal injury is associated with the extracellular signal-regulated kinase-1/2- receptor-interacting protein kinase 3 (ERK1/2-RIP3) pathway.

Methods: The cellular and subcellular localization of molecules involved in the cell death pathway, including RAGE, ERK1/2, FLIP, and RIP3, was determined with immunohistochemistry of cryosections of IR-injured retina from 2-month-old Long Evans rats.

Time-dependent Gene Profiling Indicates the Presence of Different Phases for Ischemia/Reperfusion Injury in Retina.

Ischemia/reperfusion (IR) injury has been associated with several retinal pathologies, and a few genes/gene products have been linked to IR injury. However, the big picture of temporal changes, regarding the affected gene networks, pathways, and processes remains to be determined. The purpose of the present study was to investigate initial, intermediate, and later stages to characterize the etiology of IR injury in terms of the pathways affected over time.

MicroRNAs in the Neural Retina.

The health and function of the visual system rely on a collaborative interaction between diverse classes of molecular regulators. One of these classes consists of transcription factors, which are known to bind to DNA and control the transcription activities of their target genes. For a long time, it was thought that the transcription factors were the only regulators of gene expression.

Cross-kingdom sequence similarities between human micro-RNAs and plant viruses.

Micro-RNAs regulate the expression of cellular and tissue phenotypes at a post-transcriptional level through a complex process involving complementary interactions between micro-RNAs and messenger-RNAs. Similar nucleotide interactions have been shown to occur as cross-kingdom events; for example, between plant viruses and plant micro-RNAs and also between animal viruses and animal micro-RNAs. In this study, this view is expanded to look for cross-kingdom similarities between plant virus and human micro-RNA sequences.

Transcriptomic analysis of the zebrafish inner ear points to growth hormone mediated regeneration following acoustic trauma.

Background: Unlike mammals, teleost fishes are capable of regenerating sensory inner ear hair cells that have been lost following acoustic or ototoxic trauma. Previous work indicated that immediately following sound exposure, zebrafish saccules exhibit significant hair cell loss that recovers to pre-treatment levels within 14 days. Following acoustic trauma in the zebrafish inner ear, we used microarray analysis to identify genes involved in inner ear repair following acoustic exposure.

Modeling microRNA-mRNA interactions using PLS regression in human colon cancer.

Background: Changes in microRNA (miRNA) expression patterns have been extensively characterized in several cancers, including human colon cancer. However, how these miRNAs and their putative mRNA targets contribute to the etiology of cancer is poorly understood. In this work, a bioinformatics computational approach with miRNA and mRNA expression data was used to identify the putative targets of miRNAs and to construct association networks between miRNAs and mRNAs to gain some insights into the underlined molecular mechanisms of human colon cancer.

Comparative in silico analyses of cpeb1-4 with functional predictions.

Background: Cytoplasmic polyadenylation element binding proteins (Cpebs) are a family of proteins that bind to defined groups of mRNAs and regulate their translation. While Cpebs were originally identified as important features of oocyte maturation, recent interest is due to their prospective roles in neural system plasticity.

Results: In this study we made use of bioinformatic tools and methods including NCBI Blast, UCSC Blat, and Invitrogen Vector NTI to comprehensively analyze all known isoforms of four mouse Cpeb paralogs extracted from the national UniGene, UniProt, and NCBI protein databases.

Genomic profiling of messenger RNAs and microRNAs reveals potential mechanisms of TWEAK-induced skeletal muscle wasting in mice.

Background: Skeletal muscle wasting is a devastating complication of several physiological and pathophysiological conditions. Inflammatory cytokines play an important role in the loss of skeletal muscle mass in various chronic diseases. We have recently reported that proinflammatory cytokine TWEAK is a major muscle-wasting cytokine.

Characterization of the transcripts and protein isoforms for cytoplasmic polyadenylation element binding protein-3 (CPEB3) in the mouse retina.

Background: Cytoplasmic polyadenylation element binding proteins (CPEBs) regulate translation by binding to regulatory motifs of defined mRNA targets. This translational mechanism has been shown to play a critical role in oocyte maturation, early development, and memory formation in the hippocampus. Little is known about the presence or functions of CPEBs in the retina.

Glutamate-induced NFkappaB activation in the retina.

Purpose: To determine the distribution and glutamate-mediated activation of nuclear factor (NF) kappaB members in the retina and pan-purified retinal ganglion cells (RGCs) and to characterize steps in the signal transduction events that lead to NFkappaB activation.

Methods: Retinal expression patterns and RGCs were evaluated for five NFkappaB proteins with the aid of immunohistochemistry. Retinal explants or RGCs were treated with glutamate with or without the presence of the NDMA receptor antagonist memantine, the calcium chelator EGTA, or a specific inhibitor for calcium/calmodulin-dependent protein kinase-II (CaMKII).

Regulatory module network of basic/helix-loop-helix transcription factors in mouse brain.

Background: The basic/helix-loop-helix (bHLH) proteins are important components of the transcriptional regulatory network, controlling a variety of biological processes, especially the development of the central nervous system. Until now, reports describing the regulatory network of the bHLH transcription factor (TF) family have been scarce. In order to understand the regulatory mechanisms of bHLH TFs in mouse brain, we inferred their regulatory network from genome-wide gene expression profiles with the module networks method.

CaMKIIalphaB mediates a survival response in retinal ganglion cells subjected to a glutamate stimulus.

Purpose: During N-methyl-d-aspartate-induced cell death in the neural retina, levels of the nuclear isoform of CaMKIIalpha, CaMKIIalphaB, previously reported to be detected only in the midbrain and diencephalon, become elevated. The purpose of this study was to investigate whether CaMKIIalphaB is present specifically in retinal ganglion cells (RGCs) and to determine whether it can be implicated in the cell death or cell survival of signal transduction pathways.

Methods: Pan-purified RGCs were obtained from the retinas of postnatal day (P)6 to P8 Sprague-Dawley rats.

Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3.

Increased chondroitin sulfate proteoglycan (CSPG) expression in the vicinity of a spinal cord injury (SCI) is a primary participant in axonal regeneration failure. However, the presence of similar increases of CSPG expression in denervated synaptic targets well away from the primary lesion and the subsequent impact on regenerating axons attempting to approach deafferented neurons have not been studied. Constitutively expressed CSPGs within the extracellular matrix and perineuronal nets of the adult rat dorsal column nuclei (DCN) were characterized using real-time PCR, Western blot analysis and immunohistochemistry.

Analysis of probe level patterns in Affymetrix microarray data.

Background: Microarrays have been used extensively to analyze the expression profiles for thousands of genes in parallel. Most of the widely used methods for analyzing Affymetrix Genechip microarray data, including RMA, GCRMA and Model Based Expression Index (MBEI), summarize probe signal intensity data to generate a single measure of expression for each transcript on the array. In contrast, other methods are applied directly to probe intensities, negating the need for a summarization step.

Microarray reveals complement components are regulated in the serum-deprived rat retinal ganglion cell line.

Purpose: Glaucoma is a progressive eye disease that leads to blindness due to loss of retinal ganglion cells (RGCs). There are difficulties in using primary cultures of purified RGC to study this pathophysiology. RGC-5, a transformed not RGC line, expresses several markers characteristic of the RGCs.

The role of CaMKII in BDNF-mediated neuroprotection of retinal ganglion cells (RGC-5).

The purpose of the study is to determine if expression or secretion of brain-derived neurotrophic factor (BDNF) in retinal ganglion cells (RGC-5) is mediated by NFkappaB or Ca2+/calmodulin-dependent protein kinase II (CaMKII). RGC-5 cells were exposed to 1 mM glutamate for various periods of time, in the presence or absence of prospective regulatory molecules. BDNF mRNA and protein expression were assessed with the aid of real-time PCR and immunoblots, respectively, and BDNF secretion was determined by ELISA.

Retinal ganglion cell death and neuroprotection: Involvement of the CaMKIIalpha gene.

The purpose of this study is to determine if calcium/calmodulin-dependent protein kinase-II (CaMKII) plays a role in neuronal cell death and if inhibition of this kinase affords some neuroprotection in the RGC-5 retinal ganglion cell line. The RGC-5 cells were treated with glutamate at various concentrations for increasing increments of time. Cytotoxicity was assayed by measuring the lactate dehydrogenase (LDH) leakage from non-viable cells and TUNEL assays.

MPrime: efficient large scale multiple primer and oligonucleotide design for customized gene microarrays.

Background: Enhancements in sequencing technology have recently yielded assemblies of large genomes including rat, mouse, human, fruit fly, and zebrafish. The availability of large-scale genomic and genic sequence data coupled with advances in microarray technology have made it possible to study the expression of large numbers of sequence products under several different conditions in days where traditional molecular biology techniques might have taken months, or even years. Therefore, to efficiently study a number of gene products associated with a disease, pathway, or other biological process, it is necessary to be able to design primer pairs or oligonucleotides en masse rather than using a time consuming and laborious gene-by-gene method.

Human adult olfactory neuroepithelial derived progenitors retain telomerase activity and lack apoptotic activity.

Olfactory epithelium (OE) contains a population of progenitors responsible for its life-long regenerative capacity. Procedures for the isolation of these progenitors have been established [F.J.

Enhanced expression of TNF-R1 protein in NMDA-mediated cell death in the retina.

Multiple apoptosis-related genes are expressed in the retina after exposure to N-methyl-D-aspartic acid (NMDA). For example, the mRNAs for TNF-R1, FasL, and Nur77 are up-regulated between 2.8 and 7-fold [Mol.

Developmentally regulated expression of CaMKII and iGluRs in the rat retina.

Calcium/calmodulin-dependent protein kinase II (CaMKII) and the ionotropic glutamate receptors (iGluRs) have been shown to be pivotal in the maturation of synapses during development of the central nervous system. The purpose of the current study was to assay the expression profiles of these molecules during the development of the rat retina. The mRNA levels of CaMKII were determined by the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method.