Stuart Sealfon

..This chapter provides an overview of the methodology and applications of RNA and DNA microarrays in various areas of biological research...

..Furthermore, knockdown of Brms1L significantly attenuated GnRH-induced FSHβ expression. Thus, our findings indicate that the expression of Brms1L depends on β-catenin activity and contributes to FSHβ induction by GnRH...

..Recent studies implicate these complexes in the responses to some therapeutic drugs and drugs of abuse, and raise the possibility that they may be involved in mediating functional selectivity...

..Current pathway diagrams lack either comprehensiveness, or an open-access editorial interface. Hence, there is a need for a dependable, expertly curated knowledgebase that integrates this information into a map of signaling networks...

..The BioPP suite is available for private use and for depositing knowledge-bases into a newly created public repository...

..Various unsupervised heuristic approaches that have been developed such as affinity propagation are too expensive to be applied to datasets on the order of 106 points that are often generated by high throughput experiments...

..quot; The lecture begins with a discussion of the major classes of GPCRs and then proceeds to describe the mechanisms of receptor diversity, ligand interaction, desensitization, coupling, and mutations associated with human diseases...

..CONCLUSIONS: MDS mapping based on correlation in conjunction with TF enrichment analysis represents a useful computational method to generate predictions underlying gene coregulation across a population...

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..These results suggest that abnormalities in p53 signaling play a role in dopaminergic cell death induced by proteasome inhibition and may be relevant to neurodegeneration in PD...

..The advantages and disadvantages of these methods are discussed. These methods are applied to gene expression data from two microarray studies and the properties of these multiple testing procedures are compared...

..TNF-alpha increases the expression of these genes in vitro but has not been investigated in vivo...

..More generally, our results show how a genetic program can be temporally controlled through a single regulatory network to achieve the large-scale genetic reprogramming characteristic of cell-state transitions...

..These regulatory changes indicate that the 2AR-mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis...

..Our results demonstrate that chemicals acting at the 5-HT2AR induce specific cellular response patterns in vivo that are reflected in unique changes in the somatosensory cortex transcriptome...

..RIG-I knockdown caused a 75% reduction in the induction of IFNβ mRNA compared with the negative control siRNA. This protocol should be a valuable tool for probing the immune response pathways activated in human DCs...

..In this review, we summarize the current knowledge, as well as unresolved questions, regarding agonist-trafficking and the mechanism of action of hallucinogenic drugs...

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..Although further in vivo study is needed, the characteristics of the AVDC suggest that it is well suited to play a role in the early innate-adaptive transition of the immune system...

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..These results suggest that Y7.53 and Y7.60 contribute to a common functional microdomain connecting helices 7 and 8 that influences the switching of the 5HT2C receptor among multiple active and inactive conformations...

..Recent results on the receptor, signalling and circuit mechanisms underlying the response to psychedelic and antipsychotic drugs might lead to unification of the serotonin and glutamate neurochemical hypotheses of schizophrenia...

..In addition, we have used multiplex enzyme-linked immunosorbent assays to measure secreted proteins. We demonstrate the validity of this technique and document its potential for use with blood from human study populations...

..These results support the hypothesis that specific dopamine agonists stabilize distinct conformations of the D2 receptor that differ in their coupling to G-proteins and to a cytoprotective c-Src/EGFR-mediated PI-3 kinase/Akt pathway...

..Our observations also support the potential use of NS1 mutant influenza viruses as live attenuated influenza virus vaccines...

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..These results explain the basis for variation in cellular responses in an important mammalian signaling pathway leading to gene induction...

..These studies suggest that the individual cell rapidly and stochastically processes the oxidative stress stimulus, leading to an all-or-none cytoprotective or pro-apoptotic signaling response...

..3-fold differences in transcript expression between RNA samples from treatment- and control groups and was applicable to highly heterogenous tissue sources such as hypothalamus and cerebral cortex...

..PLACA uses the results of experiments that are feasible for any signaling network to predict the functional topology of the network and to identify novel relationships...

..This strongly suggests that type I IFN functions not only to reduce viral replication in these immune cells, but also to promote greater DC activation during influenza virus infections...

..We propose that information transfer in the gonadotrope depends on robust signaling modules that serve to integrate events at different time scales across cytoplasmic and nuclear compartments...

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..Our study demonstrates systematic bias of microarray measurements and identifies a calibration function that improves the accuracy of cDNA array data...

..The distribution of epsilon-sarcoglycan in the mouse brain suggests that the symptom complex of M-D may be related to the effects of decreased epsilon-sarcoglycan activity on the development or function of monoaminergic neurons...

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..This paper reviews the status of general knowledge of mGluR2 and mGluR3 in the psychopharmacology, genetics and neuropathology of schizophrenia...

..These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens...

..We propose that PEA-15 represents a novel point of convergence of the PKC and MAPK/ERK pathways under GnRH stimulation. PKC, ERK, and PEA-15 form an AND logic gate that shapes the response of the gonadotrope cell to GnRH...

..These studies indicate that certain dopamine agonists can complex with D(2) receptors to preferentially transactivate neuroprotective signalling pathways and to mediate increased cell survival...

..The hybrid response mechanism improves the reliability of noisy reproductive signal transmission from the brain to the pituitary...

..These results suggest that Nipah virus has evolved a unique immune-antagonist strategy that benefits from controlled expression of multiple antagonist proteins with various potencies...

..The GnRHR-signaling network is openly accessible at http://tsb.mssm.edu/pathwayPublisher/GnRHR_Pathway/GnRHR_Pathway_ index.html...

..These findings indicate a specific role for cortical 5HT2AR function in the modulation of conflict anxiety, consistent with models of cortical, "top-down" influences on risk assessment...

..These results suggest a mechanism whereby synaptic stimulation, by signaling through the mTOR pathway, produces an increase in dendritic translational capacity that contributes to LTP maintenance...

..These findings suggest the importance of the microtranscriptome in gene control in the gonadotrope and implicate miR-132 and miR-212 in the regulation of GnRH-stimulated biosynthetic response...

..Because BMP2 is expressed in the adult mouse pituitary, it may act as critical paracrine co-regulator of FSH synthesis by gonadotropes...

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..The institution provides a fertile environment for this training program as well as specific resources to enhance this important educational endeavor. ..

..These parallel investigations are highly synergistic and may result in fundamental new insight into the mechanisms underlying signaling specificity of the GnRHR system. ..

..Al these interrelated investigations seek novel insight into the molecular mechanisms underlying the action of GnRH analogs and can provide the basis for the rational design of novel therapeutic approaches to modulate receptor activity. ..

..The goal of this research is to generate detailed datasets and predictive models of these cells to help improve the treatment of these conditions. ..