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  1. Article ; Online: Infrared neural stimulation with 7T fMRI: A rapid in vivo method for mapping cortical connections of primate amygdala.

    Shi, Sunhang / Xu, Augix Guohua / Rui, Yun-Yun / Zhang, Xiaotong / Romanski, Lizabeth M / Gothard, Katalin M / Roe, Anna Wang

    NeuroImage

    2021  Volume 231, Page(s) 117818

    Abstract: We have previously shown that INS-fMRI is a rapid method for mapping mesoscale brain networks in the macaque monkey brain. Focal stimulation of single cortical sites led to the activation of connected cortical locations, resulting in a global ... ...

    Abstract We have previously shown that INS-fMRI is a rapid method for mapping mesoscale brain networks in the macaque monkey brain. Focal stimulation of single cortical sites led to the activation of connected cortical locations, resulting in a global connectivity map. Here, we have extended this method for mapping brainwide networks following stimulation of single subcortical sites. As a testbed, we focused on the basal nucleus of the amygdala in the macaque monkey. We describe methods to target basal nucleus locations with submillimeter precision, pulse train stimulation methods, and statistical tests for assessing non-random nature of activations. Using these methods, we report that stimulation of precisely targeted loci in the basal nucleus produced sparse and specific activations in the brain. Activations were observed in the insular and sensory association cortices as well as activations in the cingulate cortex, consistent with known anatomical connections. What is new here is that the activations were focal and, in some cases, exhibited shifting topography with millimeter shifts in stimulation site. The precision of the method enables networks mapped from different nearby sites in the basal nucleus to be distinguished. While further investigation is needed to improve the sensitivity of this method, our analyses do support the reproducibility and non-random nature of some of the activations. We suggest that INS-fMRI is a promising method for mapping large-scale cortical and subcortical networks at high spatial resolution.
    MeSH term(s) Animals ; Basolateral Nuclear Complex/diagnostic imaging ; Basolateral Nuclear Complex/physiology ; Brain Mapping/methods ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/physiology ; Infrared Rays ; Macaca ; Magnetic Resonance Imaging/methods ; Nerve Net/diagnostic imaging ; Nerve Net/physiology ; Primates
    Language English
    Publishing date 2021-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1147767-2
    ISSN 1095-9572 ; 1053-8119
    ISSN (online) 1095-9572
    ISSN 1053-8119
    DOI 10.1016/j.neuroimage.2021.117818
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Mechanisms of dietary response in mice and primates: a role for EGR1 in regulating the reaction to human-specific nutritional content.

    Weng, Kai / Hu, Haiyang / Xu, Augix Guohua / Khaitovich, Philipp / Somel, Mehmet

    PloS one

    2012  Volume 7, Issue 8, Page(s) e43915

    Abstract: Background: Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question ... ...

    Abstract Background: Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees.
    Results: Using mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1) as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa.
    Conclusion: Our results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies.
    MeSH term(s) Animals ; Diet ; Early Growth Response Protein 1/genetics ; Early Growth Response Protein 1/metabolism ; Gene Expression ; Humans ; Liver/metabolism ; Mice ; Pan troglodytes ; Transcription, Genetic ; Transcriptome
    Chemical Substances EGR1 protein, human ; Early Growth Response Protein 1
    Language English
    Publishing date 2012-08-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0043915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Focal infrared neural stimulation with high-field functional MRI: A rapid way to map mesoscale brain connectomes.

    Xu, Augix Guohua / Qian, Meizhen / Tian, Feiyan / Xu, Bin / Friedman, Robert M / Wang, Jianbao / Song, Xuemei / Sun, Yi / Chernov, Mykyta M / Cayce, Jonathan M / Jansen, E Duco / Mahadevan-Jansen, Anita / Zhang, Xiaotong / Chen, Gang / Roe, Anna Wang

    Science advances

    2019  Volume 5, Issue 4, Page(s) eaau7046

    Abstract: We have developed a way to map brain-wide networks using focal pulsed infrared neural stimulation in ultrahigh-field magnetic resonance imaging (MRI). The patterns of connections revealed are similar to those of connections previously mapped with ... ...

    Abstract We have developed a way to map brain-wide networks using focal pulsed infrared neural stimulation in ultrahigh-field magnetic resonance imaging (MRI). The patterns of connections revealed are similar to those of connections previously mapped with anatomical tract tracing methods. These include connections between cortex and subcortical locations and long-range cortico-cortical connections. Studies of local cortical connections reveal columnar-sized laminar activation, consistent with feed-forward and feedback projection signatures. This method is broadly applicable and can be applied to multiple areas of the brain in different species and across different MRI platforms. Systematic point-by-point application of this method may lead to fundamental advances in our understanding of brain connectomes.
    MeSH term(s) Algorithms ; Animals ; Brain/diagnostic imaging ; Brain/physiology ; Brain Mapping ; Cats ; Connectome ; Electrophysiology ; Image Processing, Computer-Assisted/methods ; Infrared Rays ; Magnetic Resonance Imaging ; Neural Pathways ; Neurons/physiology ; Saimiri ; Visual Cortex/diagnostic imaging
    Language English
    Publishing date 2019-04-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.aau7046
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Development and application of a modified dynamic time warping algorithm (DTW-S) to analyses of primate brain expression time series.

    Yuan, Yuan / Chen, Yi-Ping Phoebe / Ni, Shengyu / Xu, Augix Guohua / Tang, Lin / Vingron, Martin / Somel, Mehmet / Khaitovich, Philipp

    BMC bioinformatics

    2011  Volume 12, Page(s) 347

    Abstract: Background: Comparing biological time series data across different conditions, or different specimens, is a common but still challenging task. Algorithms aligning two time series represent a valuable tool for such comparisons. While many powerful ... ...

    Abstract Background: Comparing biological time series data across different conditions, or different specimens, is a common but still challenging task. Algorithms aligning two time series represent a valuable tool for such comparisons. While many powerful computation tools for time series alignment have been developed, they do not provide significance estimates for time shift measurements.
    Results: Here, we present an extended version of the original DTW algorithm that allows us to determine the significance of time shift estimates in time series alignments, the DTW-Significance (DTW-S) algorithm. The DTW-S combines important properties of the original algorithm and other published time series alignment tools: DTW-S calculates the optimal alignment for each time point of each gene, it uses interpolated time points for time shift estimation, and it does not require alignment of the time-series end points. As a new feature, we implement a simulation procedure based on parameters estimated from real time series data, on a series-by-series basis, allowing us to determine the false positive rate (FPR) and the significance of the estimated time shift values. We assess the performance of our method using simulation data and real expression time series from two published primate brain expression datasets. Our results show that this method can provide accurate and robust time shift estimates for each time point on a gene-by-gene basis. Using these estimates, we are able to uncover novel features of the biological processes underlying human brain development and maturation.
    Conclusions: The DTW-S provides a convenient tool for calculating accurate and robust time shift estimates at each time point for each gene, based on time series data. The estimates can be used to uncover novel biological features of the system being studied. The DTW-S is freely available as an R package TimeShift at http://www.picb.ac.cn/Comparative/data.html.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Animals ; Cerebellum/growth & development ; Cerebellum/metabolism ; Child ; Child, Preschool ; Computer Simulation ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Humans ; Infant ; Macaca mulatta/genetics ; Macaca mulatta/metabolism ; Middle Aged ; Pan troglodytes/embryology ; Pan troglodytes/metabolism ; Prefrontal Cortex/growth & development ; Prefrontal Cortex/metabolism ; Primates ; Time ; Young Adult
    Language English
    Publishing date 2011-08-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041484-5
    ISSN 1471-2105 ; 1471-2105
    ISSN (online) 1471-2105
    ISSN 1471-2105
    DOI 10.1186/1471-2105-12-347
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq.

    Xu, Augix Guohua / He, Liu / Li, Zhongshan / Xu, Ying / Li, Mingfeng / Fu, Xing / Yan, Zheng / Yuan, Yuan / Menzel, Corinna / Li, Na / Somel, Mehmet / Hu, Hao / Chen, Wei / Pääbo, Svante / Khaitovich, Philipp

    PLoS computational biology

    2010  Volume 6, Page(s) e1000843

    Abstract: Transcription is the first step connecting genetic information with an organism's phenotype. While expression of annotated genes in the human brain has been characterized extensively, our knowledge about the scope and the conservation of transcripts ... ...

    Abstract Transcription is the first step connecting genetic information with an organism's phenotype. While expression of annotated genes in the human brain has been characterized extensively, our knowledge about the scope and the conservation of transcripts located outside of the known genes' boundaries is limited. Here, we use high-throughput transcriptome sequencing (RNA-Seq) to characterize the total non-ribosomal transcriptome of human, chimpanzee, and rhesus macaque brain. In all species, only 20-28% of non-ribosomal transcripts correspond to annotated exons and 20-23% to introns. By contrast, transcripts originating within intronic and intergenic repetitive sequences constitute 40-48% of the total brain transcriptome. Notably, some repeat families show elevated transcription. In non-repetitive intergenic regions, we identify and characterize 1,093 distinct regions highly expressed in the human brain. These regions are conserved at the RNA expression level across primates studied and at the DNA sequence level across mammals. A large proportion of these transcripts (20%) represents 3'UTR extensions of known genes and may play roles in alternative microRNA-directed regulation. Finally, we show that while transcriptome divergence between species increases with evolutionary time, intergenic transcripts show more expression differences among species and exons show less. Our results show that many yet uncharacterized evolutionary conserved transcripts exist in the human brain. Some of these transcripts may play roles in transcriptional regulation and contribute to evolution of human-specific phenotypic traits.
    MeSH term(s) Animals ; Cerebellum/chemistry ; Chromosome Mapping ; Cluster Analysis ; DNA, Intergenic/genetics ; Gene Expression Profiling ; Humans ; Macaca/genetics ; Male ; Mice ; Models, Genetic ; Pan troglodytes/genetics ; Phenotype ; Repetitive Sequences, Nucleic Acid/genetics ; Sequence Alignment ; Sequence Analysis, RNA ; Species Specificity
    Chemical Substances DNA, Intergenic
    Language English
    Publishing date 2010-07-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1000843
    Database MEDical Literature Analysis and Retrieval System OnLINE

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