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Molecular and cellular reorganization of neural circuits in the human lineage (2017)

Sousa, A. M. M., Zhu, Y., Raghanti, M. A., Kitchen, R. R., Onorati, M., Tebbenkamp, A. T. N., Stutz, B., Meyer, K. A., Li, M., Kawasawa, Y. I., Liu, F., Perez, R. G., Mele, M., Carvalho, T., Skarica, M., Gulden, F. O., Pletikos, M., Shibata, A., Stephenson, A. R., Edler, M. K., Ely, J. J., Elsworth, J. D., Horvath, T. L., Hof, P. R., Hyde, T. M., Kleinman, J. E., Weinberger, D. R., Reimers, M., Lifton, R. P., Mane, S. M., Noonan, J. P., State, M. W., Lein, E. S., Knowles, J. A., Marques-Bonet, T., Sherwood, C. C., Gerstein, M. B., Sestan, N.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2017-11-24

Beschreibung: To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type–specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease.

Schlagwort(e): Neuroscience

Print ISSN: 0036-8075

Digitale ISSN: 1095-9203

Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5 (2017)

Griffin, E. A., Melas, P. A., Zhou, R., Li, Y., Mercado, P., Kempadoo, K. A., Stephenson, S., Colnaghi, L., Taylor, K., Hu, M.-C., Kandel, E. R., Kandel, D. B.

American Association for the Advancement of Science (AAAS)

In: Science Advances

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Publikationsdatum: 2017-11-02

Beschreibung: Addiction to cocaine is commonly preceded by experiences with legal or decriminalized drugs, such as alcohol, nicotine, and marijuana. The biological mechanisms by which these gateway drugs contribute to cocaine addiction are only beginning to be understood. We report that in the rat, prior alcohol consumption results in enhanced addiction-like behavior to cocaine, including continued cocaine use despite aversive consequences. Conversely, prior cocaine use has no effect on alcohol preference. Long-term, but not short-term, alcohol consumption promotes proteasome-mediated degradation of the nuclear histone deacetylases HDAC4 and HDAC5 in the nucleus accumbens, a brain region critical for reward-based memory. Decreased nuclear HDAC activity results in global H3 acetylation, creating a permissive environment for cocaine-induced gene expression. We also find that selective degradation of HDAC4 and HDAC5, facilitated by the class II–specific HDAC inhibitor MC1568, enhances compulsive cocaine self-administration. These results parallel our previously reported findings that the gateway drug nicotine enhances the behavioral effects of cocaine via HDAC inhibition. Together, our findings suggest a shared mechanism of action for the gateway drugs alcohol and nicotine, and reveal a novel mechanism by which environmental factors may alter the epigenetic landscape of the reward system to increase vulnerability to cocaine addiction.

Digitale ISSN: 2375-2548

Thema: Allgemeine Naturwissenschaft

Publiziert von American Association for the Advancement of Science (AAAS)

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Bragg coherent diffractive imaging of single-grain defect dynamics in polycrystalline films (2017)

Yau, A., Cha, W., Kanan, M. W., Stephenson, G. B., Ulvestad, A.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2017-05-19

Beschreibung: Polycrystalline material properties depend on the distribution and interactions of their crystalline grains. In particular, grain boundaries and defects are crucial in determining their response to external stimuli. A long-standing challenge is thus to observe individual grains, defects, and strain dynamics inside functional materials. Here we report a technique capable of revealing grain heterogeneity, including strain fields and individual dislocations, that can be used under operando conditions in reactive environments: grain Bragg coherent diffractive imaging (gBCDI). Using a polycrystalline gold thin film subjected to heating, we show how gBCDI resolves grain boundary and dislocation dynamics in individual grains in three-dimensional detail with 10-nanometer spatial and subangstrom displacement field resolution. These results pave the way for understanding polycrystalline material response under external stimuli and, ideally, engineering particular functions.

Schlagwort(e): Materials Science

Print ISSN: 0036-8075

Digitale ISSN: 1095-9203

Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors (2017)

Villani, A.-C., Satija, R., Reynolds, G., Sarkizova, S., Shekhar, K., Fletcher, J., Griesbeck, M., Butler, A., Zheng, S., Lazo, S., Jardine, L., Dixon, D., Stephenson, E., Nilsson, E., Grundberg, I., McDonald, D., Filby, A., Li, W., De Jager, P. L., Rozenblatt-Rosen, O., Lane, A. A., Haniffa, M., Regev, A., Hacohen, N.

American Association for the Advancement of Science (AAAS)

In: Science

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Publikationsdatum: 2017-04-21

Beschreibung: Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C + subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease.

Schlagwort(e): Immunology, Online Only

Print ISSN: 0036-8075

Digitale ISSN: 1095-9203

Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von American Association for the Advancement of Science (AAAS)

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