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  • 1
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    In vivo brain GPCR signaling elucidated by phosphoproteomics (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-06-22
    Description: A systems view of G protein–coupled receptor (GPCR) signaling in its native environment is central to the development of GPCR therapeutics with fewer side effects. Using the kappa opioid receptor (KOR) as a model, we employed high-throughput phosphoproteomics to investigate signaling induced by structurally diverse agonists in five mouse brain regions. Quantification of 50,000 different phosphosites provided a systems view of KOR in vivo signaling, revealing novel mechanisms of drug action. Thus, we discovered enrichment of the mechanistic target of rapamycin (mTOR) pathway by U-50,488H, an agonist causing aversion, which is a typical KOR-mediated side effect. Consequently, mTOR inhibition during KOR activation abolished aversion while preserving beneficial antinociceptive and anticonvulsant effects. Our results establish high-throughput phosphoproteomics as a general strategy to investigate GPCR in vivo signaling, enabling prediction and modulation of behavioral outcomes.
    Keywords: Cell Biology, Neuroscience, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    NextGen Voices: Quality mentoring (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-10-05
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Control of self-assembly of DNA tubules through integration of gold nanoparticles (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-03
    Description: The assembly of nanoparticles into three-dimensional (3D) architectures could allow for greater control of the interactions between these particles or with molecules. DNA tubes are known to form through either self-association of multi-helix DNA bundle structures or closing up of 2D DNA tile lattices. By the attachment of single-stranded DNA to gold nanoparticles, nanotubes of various 3D architectures can form, ranging in shape from stacked rings to single spirals, double spirals, and nested spirals. The nanoparticles are active elements that control the preference for specific tube conformations through size-dependent steric repulsion effects. For example, we can control the tube assembly to favor stacked-ring structures using 10-nanometer gold nanoparticles. Electron tomography revealed a left-handed chirality in the spiral tubes, double-wall tube features, and conformational transitions between tubes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893555/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893555/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharma, Jaswinder -- Chhabra, Rahul -- Cheng, Anchi -- Brownell, Jonathan -- Liu, Yan -- Yan, Hao -- P41 RR-01081/RR/NCRR NIH HHS/ -- P41 RR000592/RR/NCRR NIH HHS/ -- P41 RR017573/RR/NCRR NIH HHS/ -- P41 RR017573-086704/RR/NCRR NIH HHS/ -- RR17573/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):112-6. doi: 10.1126/science.1165831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Single Molecule Biophysics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19119229" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*chemistry ; Electron Microscope Tomography ; *Gold ; Image Processing, Computer-Assisted ; Inverted Repeat Sequences ; Metal Nanoparticles/*chemistry ; Nanotubes/*chemistry ; Nucleic Acid Conformation ; Thermodynamics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    V1 neurons signal acquisition of an internal representation of stimulus location (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-06-14
    Description: A fundamental aspect of visuomotor behavior is deciding where to look or move next. Under certain conditions, the brain constructs an internal representation of stimulus location on the basis of previous knowledge and uses it to move the eyes or to make other movements. Neuronal responses in primary visual cortex were modulated when such an internal representation was acquired: Responses to a stimulus were affected progressively by sequential presentation of the stimulus at one location but not when the location was varied randomly. Responses of individual neurons were spatially tuned for gaze direction and tracked the Bayesian probability of stimulus appearance. We propose that the representation arises in a distributed cortical network and is associated with systematic changes in response selectivity and dynamics at the earliest stages of cortical visual processing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharma, Jitendra -- Dragoi, Valentin -- Tenenbaum, Joshua B -- Miller, Earl K -- Sur, Mriganka -- New York, N.Y. -- Science. 2003 Jun 13;300(5626):1758-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. jeetu@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805552" target="_blank"〉PubMed〈/a〉
    Keywords: Analysis of Variance ; Animals ; Bayes Theorem ; Cues ; Electrophysiology ; Fixation, Ocular/*physiology ; Humans ; Macaca mulatta ; Neurons/*physiology ; Photic Stimulation ; Probability ; Random Allocation ; Saccades/*physiology ; Visual Cortex/cytology/*physiology ; Visual Perception/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Orientation maps of subjective contours in visual cortex (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-12-20
    Description: Responses to subjective contours in visual cortical areas V1 and V2 in adult cats were investigated by optical imaging of intrinsic signals and single-unit recording. Both V1 and V2 contain maps of the orientation of subjective gratings that have their basis in specific kinds of neuronal responses to subjective orientations. A greater proportion of neurons in V2 than in V1 show a robust response to subjective edges. Through the use of subjective stimuli in which the orientation of the luminance component is invariant, an unmasked V1 response to subjective edges alone can be demonstrated. The data indicate that the processing of subjective contours begins as early as V1 and continues progressively in higher cortical areas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheth, B R -- Sharma, J -- Rao, S C -- Sur, M -- EY07023/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1996 Dec 20;274(5295):2110-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. msur@wccf.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8953048" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Brain Mapping ; Cats ; *Form Perception ; Image Processing, Computer-Assisted ; Light ; Neurons/*physiology ; Visual Cortex/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Self-organized stress patterns drive state transitions in actin cortices (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-06-07
    Description: Biological functions rely on ordered structures and intricately controlled collective dynamics. This order in living systems is typically established and sustained by continuous dissipation of energy. The emergence of collective patterns of motion is unique to nonequilibrium systems and is a manifestation of dynamic steady states. Mechanical resilience of animal cells is largely controlled by the actomyosin cortex. The cortex provides stability but is, at the same time, highly adaptable due to rapid turnover of its components. Dynamic functions involve regulated transitions between different steady states of the cortex. We find that model actomyosin cortices, constructed to maintain turnover, self-organize into distinct nonequilibrium steady states when we vary cross-link density. The feedback between actin network structure and organization of stress-generating myosin motors defines the symmetries of the dynamic steady states. A marginally cross-linked state displays divergence-free long-range flow patterns. Higher cross-link density causes structural symmetry breaking, resulting in a stationary converging flow pattern. We track the flow patterns in the model actomyosin cortices using fluorescent single-walled carbon nanotubes as novel probes. The self-organization of stress patterns we have observed in a model system can have direct implications for biological functions.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Flexible active-matrix organic light-emitting diode display enabled by MoS2 thin-film transistor (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-04-21
    Description: Atomically thin molybdenum disulfide (MoS 2 ) has been extensively investigated in semiconductor electronics but has not been applied in a backplane circuitry of organic light-emitting diode (OLED) display. Its applicability as an active drive element is hampered by the large contact resistance at the metal/MoS 2 interface, which hinders the transport of carriers at the dielectric surface, which in turn considerably deteriorates the mobility. Modified switching device architecture is proposed for efficiently exploiting the high- k dielectric Al 2 O 3 layer, which, when integrated in an active matrix, can drive the ultrathin OLED display even in dynamic folding states. The proposed architecture exhibits 28 times increase in mobility compared to a normal back-gated thin-film transistor, and its potential as a wearable display attached to a human wrist is demonstrated.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Transformation of shock-compressed graphite to hexagonal diamond in nanoseconds (2017)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2017-10-28
    Description: The graphite-to-diamond transformation under shock compression has been of broad scientific interest since 1961. The formation of hexagonal diamond (HD) is of particular interest because it is expected to be harder than cubic diamond and due to its use in terrestrial sciences as a marker at meteorite impact sites. However, the formation of diamond having a fully hexagonal structure continues to be questioned and remains unresolved. Using real-time (nanosecond), in situ x-ray diffraction measurements, we show unequivocally that highly oriented pyrolytic graphite, shock-compressed along the c axis to 50 GPa, transforms to highly oriented elastically strained HD with the (100) HD plane parallel to the graphite basal plane. These findings contradict recent molecular dynamics simulation results for the shock-induced graphite-to-diamond transformation and provide a benchmark for future theoretical simulations. Additionally, our results show that an earlier report of HD forming only above 170 GPa for shocked pyrolytic graphite may lead to incorrect interpretations of meteorite impact events.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉The transition from land to water in whales and dolphins (cetaceans) was accompanied by remarkable adaptations. To reveal genomic changes that occurred during this transition, we screened for protein-coding genes that were inactivated in the ancestral cetacean lineage. We found 85 gene losses. Some of these were likely beneficial for cetaceans, for example, by reducing the risk of thrombus formation during diving (〈i〉F12〈/i〉 and 〈i〉KLKB1〈/i〉), erroneous DNA damage repair (〈i〉POLM〈/i〉), and oxidative stress–induced lung inflammation (〈i〉MAP3K19〈/i〉). Additional gene losses may reflect other diving-related adaptations, such as enhanced vasoconstriction during the diving response (mediated by 〈i〉SLC6A18〈/i〉) and altered pulmonary surfactant composition (〈i〉SEC14L3〈/i〉), while loss of 〈i〉SLC4A9〈/i〉 relates to a reduced need for saliva. Last, loss of melatonin synthesis and receptor genes (〈i〉AANAT〈/i〉, 〈i〉ASMT〈/i〉, and 〈i〉MTNR1A〈/i〉/〈i〉B〈/i〉) may have been a precondition for adopting unihemispheric sleep. Our findings suggest that some genes lost in ancestral cetaceans were likely involved in adapting to a fully aquatic lifestyle.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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