Brief Report: Excitatory and Inhibitory Brain Metabolites as Targets of Motor Cortex Transcranial Direct Current Stimulation Therapy and Predictors of Its Efficacy in Fibromyalgia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110535/1/art38945.pd

Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery

Motivation: Signaling pathways control a large variety of cellular processes. However, currently, even within the same database signaling pathways are often curated at different levels of detail. This makes comparative and cross-talk analyses difficult. Results: We present SignaLink, a database containing 8 major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster, and humans. Based on 170 review and approx. 800 research articles, we have compiled pathways with semi-automatic searches and uniform, well-documented curation rules. We found that in humans any two of the 8 pathways can cross-talk. We quantified the possible tissue- and cancer-specific activity of cross-talks and found pathway-specific expression profiles. In addition, we identified 327 proteins relevant for drug target discovery. Conclusions: We provide a novel resource for comparative and cross-talk analyses of signaling pathways. The identified multi-pathway and tissue-specific cross-talks contribute to the understanding of the signaling complexity in health and disease and underscore its importance in network-based drug target selection. Availability: http://SignaLink.orgComment: 9 pages, 4 figures, 2 tables and a supplementary info with 5 Figures and 13 Table

Linking Proteins to Signaling Pathways for Experiment Design and Evaluation

Biomedical experimental work often focuses on altering the functions of selected proteins. These changes can hit signaling pathways, and can therefore unexpectedly and non-specifically affect cellular processes. We propose PathwayLinker, an online tool that can provide a first estimate of the possible signaling effects of such changes, e.g., drug or microRNA treatments. PathwayLinker minimizes the users' efforts by integrating protein-protein interaction and signaling pathway data from several sources with statistical significance tests and clear visualization. We demonstrate through three case studies that the developed tool can point out unexpected signaling bias in normal laboratory experiments and identify likely novel signaling proteins among the interactors of known drug targets. In our first case study we show that knockdown of the Caenorhabditis elegans gene cdc-25.1 (meant to avoid progeny) may globally affect the signaling system and unexpectedly bias experiments. In the second case study we evaluate the loss-of-function phenotypes of a less known C. elegans gene to predict its function. In the third case study we analyze GJA1, an anti-cancer drug target protein in human, and predict for this protein novel signaling pathway memberships, which may be sources of side effects. Compared to similar services, a major advantage of PathwayLinker is that it drastically reduces the necessary amount of manual literature searches and can be used without a computational background. PathwayLinker is available at http://PathwayLinker.org. Detailed documentation and source code are available at the website

Initial Verification of GEOS-4 Aerosols Using CALIPSO and MODIS: Scene Classification

A-train sensors such as MODIS and MISR provide column aerosol properties, and in the process a means of estimating aerosol type (e.g. smoke vs. dust). Correct classification of aerosol type is important because retrievals are often dependent upon selection of the right aerosol model. In addition, aerosol scene classification helps place the retrieved products in context for comparisons and analysis with aerosol transport models. The recent addition of CALIPSO to the A-train now provides a means of classifying aerosol distribution with altitude. CALIPSO level 1 products include profiles of attenuated backscatter at 532 and 1064 nm, and depolarization at 532 nm. Backscatter intensity, wavelength ratio, and depolarization provide information on the vertical profile of aerosol concentration, size, and shape. Thus similar estimates of aerosol type using MODIS or MISR are possible with CALIPSO, and the combination of data from all sensors provides a means of 3D aerosol scene classification. The NASA Goddard Earth Observing System general circulation model and data assimilation system (GEOS-4) provides global 3D aerosol mass for sulfate, sea salt, dust, and black and organic carbon. A GEOS-4 aerosol scene classification algorithm has been developed to provide estimates of aerosol mixtures along the flight track for NASA's Geoscience Laser Altimeter System (GLAS) satellite lidar. GLAS launched in 2003 and did not have the benefit of depolarization measurements or other sensors from the A-train. Aerosol typing from GLAS data alone was not possible, and the GEOS-4 aerosol classifier has been used to identify aerosol type and improve the retrieval of GLAS products. Here we compare 3D aerosol scene classification using CALIPSO and MODIS with the GEOS-4 aerosol classifier. Dust, smoke, and pollution examples will be discussed in the context of providing an initial verification of the 3D GEOS-4 aerosol products. Prior model verification has only been attempted with surface mass comparisons and column optical depth from AERONET and MODIS

State-of-art neuroanatomical target analysis of high-definition and conventional tDCS montages used for migraine and pain control

Although transcranial direct current stimulation (tDCS) studies promise to modulate cortical regions associated with pain, the electric current produced usually spreads beyond the area of the electrodes’ placement. Using a forward-model analysis, this study compared the neuroanatomic location and strength of the predicted electric current peaks, at cortical and subcortical levels, induced by conventional and High-Definition-tDCS (HD-tDCS) montages developed for migraine and other chronic pain disorders. The electrodes were positioned in accordance with the 10-20 or 10-10 electroencephalogram (EEG) landmarks: motor cortex-supraorbital (M1-SO, anode and cathode over C3 and Fp2, respectively), dorsolateral prefrontal cortex bilateral (DLPFC, anode over F3, cathode over F4), vertex-occipital cortex (anode over Cz and cathode over Oz), HD-tDCS 4x1 (one anode on C3, and four cathodes over Cz, F3, T7, and P3) and HD-tDCS 2x2 (two anodes over C3/C5 and two cathodes over FC3/FC5). M1-SO produced a large current flow in the prefrontal cortex (PFC). Peaks of current flow also occurred in deeper brain structures, such as the cingulate cortex, insula, thalamus and brainstem. The same structures received significant amount of current with Cz-Oz and DLPFC tDCS. However, there were differences in the current flow to outer cortical regions. The visual cortex, cingulate and thalamus received the majority of the current flow with the Cz-Oz, while the anterior parts of the superior and middle frontal gyri displayed an intense amount of current with DLPFC montage. HD-tDCS montages enhanced the focality, producing peaks of current in subcortical areas at negligible levels. This study provides novel information regarding the neuroanatomical distribution and strength of the electric current using several tDCS montages applied for migraine and pain control. Such information may help clinicians and researchers in deciding the most appropriate tDCS montage to treat each pain disorder