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  1. Article ; Online: AdRoit is an accurate and robust method to infer complex transcriptome composition.

    Yang, Tao / Alessandri-Haber, Nicole / Fury, Wen / Schaner, Michael / Breese, Robert / LaCroix-Fralish, Michael / Kim, Jinrang / Adler, Christina / Macdonald, Lynn E / Atwal, Gurinder S / Bai, Yu

    Communications biology

    2021  Volume 4, Issue 1, Page(s) 1218

    Abstract: Bulk RNA sequencing provides the opportunity to understand biology at the whole transcriptome level without the prohibitive cost of single cell profiling. Advances in spatial transcriptomics enable to dissect tissue organization and function by genome- ... ...

    Abstract Bulk RNA sequencing provides the opportunity to understand biology at the whole transcriptome level without the prohibitive cost of single cell profiling. Advances in spatial transcriptomics enable to dissect tissue organization and function by genome-wide gene expressions. However, the readout of both technologies is the overall gene expression across potentially many cell types without directly providing the information of cell type constitution. Although several in-silico approaches have been proposed to deconvolute RNA-Seq data composed of multiple cell types, many suffer a deterioration of performance in complex tissues. Here we present AdRoit, an accurate and robust method to infer the cell composition from transcriptome data of mixed cell types. AdRoit uses gene expression profiles obtained from single cell RNA sequencing as a reference. It employs an adaptive learning approach to alleviate the sequencing technique difference between the single cell and the bulk (or spatial) transcriptome data, enhancing cross-platform readout comparability. Our systematic benchmarking and applications, which include deconvoluting complex mixtures that encompass 30 cell types, demonstrate its preferable sensitivity and specificity compared to many existing methods as well as its utilities. In addition, AdRoit is computationally efficient and runs orders of magnitude faster than most methods.
    MeSH term(s) Gene Expression Profiling/methods ; Genome ; Sensitivity and Specificity ; Transcriptome
    Language English
    Publishing date 2021-10-22
    Publishing country England
    Document type Journal Article
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-021-02739-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Expression of c-fos in hilar mossy cells of the dentate gyrus in vivo.

    Duffy, Aine M / Schaner, Michael J / Chin, Jeannie / Scharfman, Helen E

    Hippocampus

    2013  Volume 23, Issue 8, Page(s) 649–655

    Abstract: Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent--they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on ... ...

    Abstract Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent--they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on recordings in hippocampal slices. MCs project to GCs, so activity in MCs could play an important role in activating GCs. Therefore, we investigated whether MCs were active under basal conditions in vivo, using the immediate early gene c-fos as a tool. We hypothesized that MCs would exhibit c-fos expression even if rats were examined randomly, under normal housing conditions. Therefore, adult male rats were perfused shortly after removal from their home cage and transfer to the laboratory. Remarkably, most c-fos immunoreactivity (ir) was in the hilus, especially temporal hippocampus. C-fos-ir hilar cells co-expressed GluR2/3, suggesting that they were MCs. C-fos-ir MCs were robust even when the animal was habituated to the investigator and laboratory where they were euthanized. However, c-fos-ir in dorsal MCs was reduced under these circumstances, suggesting that ventral and dorsal MCs are functionally distinct. Interestingly, there was an inverse relationship between MC and GC layer c-fos expression, with little c-fos expression in the GC layer in ventral sections where MC expression was strong, and the opposite in dorsal hippocampus. The results support the hypothesis that a subset of hilar MCs are spontaneously active in vivo and provide other DG neurons with tonic depolarizing input.
    MeSH term(s) Analysis of Variance ; Animals ; Cell Count ; Dentate Gyrus/cytology ; Male ; Mossy Fibers, Hippocampal/physiology ; Neurons/metabolism ; Neuropeptide Y/metabolism ; Parvalbumins/metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism
    Chemical Substances Neuropeptide Y ; Parvalbumins ; Proto-Oncogene Proteins c-fos ; Receptors, AMPA ; glutamate receptor ionotropic, AMPA 2 (P6W5IXV8V9)
    Language English
    Publishing date 2013-05-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1074352-2
    ISSN 1098-1063 ; 1050-9631
    ISSN (online) 1098-1063
    ISSN 1050-9631
    DOI 10.1002/hipo.22138
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age.

    Duffy, Aine M / Morales-Corraliza, Jose / Bermudez-Hernandez, Keria M / Schaner, Michael J / Magagna-Poveda, Alejandra / Mathews, Paul M / Scharfman, Helen E

    Neurobiology of aging

    2014  Volume 36, Issue 1, Page(s) 134–148

    Abstract: The entorhinal cortex (EC) is one of the first brain areas to display neuropathology in Alzheimer's disease. A mouse model which simulates amyloid-β (Aβ) neuropathology, the Tg2576 mouse, was used to address these early changes. Here, we show EC ... ...

    Abstract The entorhinal cortex (EC) is one of the first brain areas to display neuropathology in Alzheimer's disease. A mouse model which simulates amyloid-β (Aβ) neuropathology, the Tg2576 mouse, was used to address these early changes. Here, we show EC abnormalities occur in 2- to 4-month-old Tg2576 mice, an age before Aβ deposition and where previous studies suggest that there are few behavioral impairments. First we show, using a sandwich enzyme-linked immunosorbent assay, that soluble human Aβ40 and Aβ42 are detectable in the EC of 2-month-old Tg2576 mice before Aβ deposition. We then demonstrate that 2- to 4-month-old Tg2576 mice are impaired at object placement, an EC-dependent cognitive task. Next, we show that defects in neuronal nuclear antigen expression and myelin uptake occur in the superficial layers of the EC in 2- to 4-month-old Tg2576 mice. In slices from Tg2576 mice that contained the EC, there were repetitive field potentials evoked by a single stimulus to the underlying white matter, and a greater response to reduced extracellular magnesium ([Mg(2+)]o), suggesting increased excitability. However, deep layer neurons in Tg2576 mice had longer latencies to antidromic activation than wild type mice. The results show changes in the EC at early ages and suggest that altered excitability occurs before extensive plaque pathology.
    MeSH term(s) Aging/metabolism ; Aging/pathology ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Animals ; Disease Models, Animal ; Entorhinal Cortex/metabolism ; Entorhinal Cortex/pathology ; Female ; Magnesium/metabolism ; Male ; Mice, Inbred Strains ; Mice, Transgenic ; Plaque, Amyloid/metabolism ; Plaque, Amyloid/pathology
    Chemical Substances Amyloid beta-Peptides ; Magnesium (I38ZP9992A)
    Language English
    Publishing date 2014-07-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604505-4
    ISSN 1558-1497 ; 0197-4580
    ISSN (online) 1558-1497
    ISSN 0197-4580
    DOI 10.1016/j.neurobiolaging.2014.07.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Immediate-early gene expression at rest recapitulates recent experience.

    Marrone, Diano F / Schaner, Michael J / McNaughton, Bruce L / Worley, Paul F / Barnes, Carol A

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2008  Volume 28, Issue 5, Page(s) 1030–1033

    Abstract: Immediate-early genes (IEGs) are tightly coupled to cellular activity and play a critical role in regulating synaptic plasticity. While encoding spatial experience, hippocampal principal cells express IEGs in a behaviorally dependent and cell-specific ... ...

    Abstract Immediate-early genes (IEGs) are tightly coupled to cellular activity and play a critical role in regulating synaptic plasticity. While encoding spatial experience, hippocampal principal cells express IEGs in a behaviorally dependent and cell-specific manner. This expression can be detected through the use of cellular compartment analysis of temporal activity by fluorescence in situ hybridization to generate estimates of cellular activity that match direct neuronal recording under comparable conditions. During rest, IEG expression continues to occur in a small number of cells, and the role of this basal expression is unknown. Imaging IEGs expressed during exploration and adjacent rest periods reveals that "constitutive" IEG expression during rest is not random. Rather, consistent with proposed memory consolidation mechanisms, it recapitulates a subset of the pattern generated by recent experience.
    MeSH term(s) Animals ; Carrier Proteins/biosynthesis ; Carrier Proteins/genetics ; Exploratory Behavior/physiology ; Gene Expression Regulation/genetics ; Gene Expression Regulation/physiology ; Genes, Immediate-Early/genetics ; Genes, Immediate-Early/physiology ; Homer Scaffolding Proteins ; Learning/physiology ; Rats ; Rats, Inbred F344 ; Rest/physiology ; Time Factors
    Chemical Substances Carrier Proteins ; Homer Scaffolding Proteins
    Language English
    Publishing date 2008-01-30
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.4235-07.2008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A selective role for ARMS/Kidins220 scaffold protein in spatial memory and trophic support of entorhinal and frontal cortical neurons.

    Duffy, Aine M / Schaner, Michael J / Wu, Synphen H / Staniszewski, Agnieszka / Kumar, Asok / Arévalo, Juan Carlos / Arancio, Ottavio / Chao, Moses V / Scharfman, Helen E

    Experimental neurology

    2011  Volume 229, Issue 2, Page(s) 409–420

    Abstract: Progressive cortical pathology is common to several neurodegenerative and psychiatric disorders. The entorhinal cortex (EC) and frontal cortex (FC) are particularly vulnerable, and neurotrophins have been implicated because they appear to be protective. ... ...

    Abstract Progressive cortical pathology is common to several neurodegenerative and psychiatric disorders. The entorhinal cortex (EC) and frontal cortex (FC) are particularly vulnerable, and neurotrophins have been implicated because they appear to be protective. A downstream signal transducer of neurotrophins, the ankyrin repeat-rich membrane spanning scaffold protein/Kidins 220 (ARMS) is expressed in the cortex, where it could play an important role in trophic support. To test this hypothesis, we evaluated mice with a heterozygous deletion of ARMS (ARMS(+/-) mice). Remarkably, the EC and FC were the regions that demonstrated the greatest defects. Many EC and FC neurons became pyknotic in ARMS(+/-) mice, so that large areas of the EC and FC were affected by 12 months of age. Areas with pyknosis in the EC and FC of ARMS(+/-) mice were also characterized by a loss of immunoreactivity to a neuronal antigen, NeuN, which has been reported after insult or injury to cortical neurons. Electron microscopy showed that there were defects in mitochondria, myelination, and multilamellar bodies in the EC and FC of ARMS(+/-) mice. Although primarily restricted to the EC and FC, pathology appeared to be sufficient to cause functional impairments, because ARMS(+/-) mice performed worse than wild-type on the Morris water maze. Comparisons of males and females showed that female mice were the affected sex in all comparisons. Taken together, the results suggest that the expression of a prominent neurotrophin receptor substrate normally protects the EC and FC, and that ARMS may be particularly important in females.
    MeSH term(s) Animals ; Entorhinal Cortex/metabolism ; Female ; Frontal Lobe/metabolism ; Immunohistochemistry ; Male ; Maze Learning/physiology ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout ; Microscopy, Electron ; Mitochondria/metabolism ; Myelin Sheath/metabolism ; Neurons/metabolism ; Sex Factors
    Chemical Substances Kidins220 protein, mouse ; Membrane Proteins
    Language English
    Publishing date 2011-03-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 207148-4
    ISSN 1090-2430 ; 0014-4886
    ISSN (online) 1090-2430
    ISSN 0014-4886
    DOI 10.1016/j.expneurol.2011.03.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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