| 1. |
- Legrain, Pierre, et al.
(author)
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The Human Proteome Project : Current State and Future Direction
- 2011
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 10:7
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Journal article (peer-reviewed)abstract
- After the successful completion of the Human Genome Project, the Human Proteome Organization has recently officially launched a global Human Proteome Project (HPP), which is designed to map the entire human protein set. Given the lack of protein-level evidence for about 30% of the estimated 20,300 protein-coding genes, a systematic global effort will be necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP research groups will use the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge bases. The HPP participants will take advantage of the output and cross-analyses from the ongoing Human Proteome Organization initiatives and a chromosome-centric protein mapping strategy, termed C-HPP, with which many national teams are currently engaged. In addition, numerous biologically driven and disease-oriented projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents, and tools for protein studies and analyses, and a stronger basis for personalized medicine. The Human Proteome Organization urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators.
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| 2. |
- Mazei-Robison, Michelle S., et al.
(author)
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Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons
- 2011
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In: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 72:6, s. 977-990
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Journal article (peer-reviewed)abstract
- While the abuse of opiate drugs continues to rise, the neuroadaptations that occur with long-term drug exposure remain poorly understood. We describe here a series of chronic morphine-induced adaptations in ventral tegmental area (VTA) dopamine neurons, which are mediated via downregulation of AKT-mTORC2 (mammalian target of rapamycin complex-2). Chronic opiates decrease the size of VTA dopamine neurons in rodents, an effect seen in humans as well, and concomitantly increase the excitability of the cells but decrease dopamine output to target regions. Chronic morphine decreases mTORC2 activity, and overexpression of Rictor, a component of mTORC2, prevents morphine-induced changes in cell morphology and activity. Further, local knockout of Rictor in VTA decreases DA soma size and reduces rewarding responses to morphine, consistent with the hypothesis that these adaptations represent a mechanism of reward tolerance. Together, these findings demonstrate a novel role for AKT-mTORC2 signaling in mediating neuroadaptations to opiate drugs of abuse.
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| 3. |
- Savitz, Sean I., et al.
(author)
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Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II
- 2011
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In: Stroke. - 0039-2499. ; 42:3, s. 825-829
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Research review (peer-reviewed)abstract
- Cell-based therapies represent a new therapeutic approach for stroke. In 2007, investigators from academia, industry leaders, and members of the National Institutes of Health crafted recommendations to facilitate the translational development of cellular therapies as a novel, emerging modality for stroke from animal studies to clinical trials. This meeting was called Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) and was modeled on the format of the Stroke Therapy Academic Industry Roundtable (STAIR) meetings. Since publication of the original STEPS guidelines, there has been an explosive growth in the number of cellular products and in the number of new laboratory discoveries that impact the safety and potential efficacy of cell therapies for stroke. Any successful development of a cell product will need to take into consideration several factors, including the preclinical safety and efficacy profile, cell characterization, delivery route, in vivo biodistribution, and mechanism of action. In 2010, a second meeting called STEPS 2 was held to bring together clinical and basic science researchers with industry, regulatory, and National Institutes of Health representatives. At this meeting, participants identified critical gaps in knowledge and research areas that require further studies, updated prior guidelines, and drafted new recommendations to create a framework to guide future investigations in cell-based therapies for stroke.
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