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  1. AU="Kory Johnson"
  2. AU="Espinoza, Gonzalo"
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  1. Article ; Online: Common features of aging fail to occur in Drosophila raised without a bacterial microbiome

    Arvind Kumar Shukla / Kory Johnson / Edward Giniger

    iScience, Vol 24, Iss 7, Pp 102703- (2021)

    2021  

    Abstract: Summary: Lifespan is limited both by intrinsic decline in vigor with age and by accumulation of external insults. There exists a general picture of the deficits of aging, one that is reflected in a pattern of age-correlated changes in gene expression ... ...

    Abstract Summary: Lifespan is limited both by intrinsic decline in vigor with age and by accumulation of external insults. There exists a general picture of the deficits of aging, one that is reflected in a pattern of age-correlated changes in gene expression conserved across species. Here, however, by comparing gene expression profiling of Drosophila raised either conventionally, or free of bacteria, we show that ∼70% of these conserved, age-associated changes in gene expression fail to occur in germ-free flies. Among the processes that fail to show time-dependent change under germ-free conditions are two aging features that are observed across phylogeny, declining expression of stress response genes and increasing expression of innate immune genes. These comprise adaptive strategies the organism uses to respond to bacteria, rather than being inevitable components of age-dependent decline. Changes in other processes are independent of the microbiome and can serve as autonomous markers of aging of the individual.
    Keywords Biological sciences ; physiology ; microbiology ; microbiome ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Lamina-specific immunohistochemical signatures in the olfactory bulb of healthy, Alzheimer’s and Parkinson’s disease patients

    Helen C. Murray / Kory Johnson / Andrea Sedlock / Blake Highet / Birger Victor Dieriks / Praju Vikas Anekal / Richard L. M. Faull / Maurice A. Curtis / Alan Koretsky / Dragan Maric

    Communications Biology, Vol 5, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: Murray et al. present a multiplexed fluorescence-based immunohistochemistry approach and use it to screen up to 100 protein markers in the human olfactory bulb from neurologically healthy, Alzheimer’s, and Parkinson’s disease patients. In doing so, they ... ...

    Abstract Murray et al. present a multiplexed fluorescence-based immunohistochemistry approach and use it to screen up to 100 protein markers in the human olfactory bulb from neurologically healthy, Alzheimer’s, and Parkinson’s disease patients. In doing so, they identify differentially expressed biomarkers in Alzheimer’s, and Parkinson’s disease.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging

    Joshua Spurrier / Arvind Kumar Shukla / Kristina McLinden / Kory Johnson / Edward Giniger

    Disease Models & Mechanisms, Vol 11, Iss

    2018  Volume 3

    Abstract: Aging is the greatest risk factor for neurodegeneration, but the connection between the two processes remains opaque. This is in part for want of a rigorous way to define physiological age, as opposed to chronological age. Here, we develop a ... ...

    Abstract Aging is the greatest risk factor for neurodegeneration, but the connection between the two processes remains opaque. This is in part for want of a rigorous way to define physiological age, as opposed to chronological age. Here, we develop a comprehensive metric for physiological age in Drosophila, based on genome-wide expression profiling. We applied this metric to a model of adult-onset neurodegeneration, increased or decreased expression of the activating subunit of the Cdk5 protein kinase, encoded by the gene Cdk5α, the ortholog of mammalian p35. Cdk5α-mediated degeneration was associated with a 27-150% acceleration of the intrinsic rate of aging, depending on the tissue and genetic manipulation. Gene ontology analysis and direct experimental tests revealed that affected age-associated processes included numerous core phenotypes of neurodegeneration, including enhanced oxidative stress and impaired proteostasis. Taken together, our results suggest that Cdk5α-mediated neurodegeneration results from accelerated aging, in combination with cell-autonomous neuronal insults. These data fundamentally recast our picture of the relationship between neurodegeneration and its most prominent risk factor, natural aging.
    Keywords Neurodegeneration ; Aging ; Cdk5 ; Drosophila ; p35 ; Cdk5α ; Medicine ; R ; Pathology ; RB1-214
    Subject code 612
    Language English
    Publishing date 2018-03-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma

    Ashish H. Shah / Sarah R. Rivas / Tara T. Doucet-O’Hare / Vaidya Govindarajan / Catherine DeMarino / Tongguang Wang / Leonel Ampie / Yong Zhang / Yeshavanth Kumar Banasavadi-Siddegowda / Stuart Walbridge / Dragan Maric / Marta Garcia-Montojo / Robert K. Suter / Myoung-Hwa Lee / Kareem A. Zaghloul / Joseph Steiner / Abdel G. Elkahloun / Jay Chandar / Deepa Seetharam /
    Jelisah Desgraves / Wenxue Li / Kory Johnson / Michael E. Ivan / Ricardo J. Komotar / Mark R. Gilbert / John D. Heiss / Avindra Nath

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 13

    Abstract: Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report ... ...

    Abstract Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor–like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2–specific long-terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target.
    Keywords Stem cells ; Virology ; Medicine ; R
    Subject code 571
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Transcriptome profiling identifies regulators of pathogenesis in collagen VI related muscular dystrophy.

    Russell J Butterfield / Diane M Dunn / Ying Hu / Kory Johnson / Carsten G Bönnemann / Robert B Weiss

    PLoS ONE, Vol 12, Iss 12, p e

    2017  Volume 0189664

    Abstract: The collagen VI related muscular dystrophies (COL6-RD), Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are among the most common congenital muscular dystrophies and are characterized by distal joint laxity and a combination of ... ...

    Abstract The collagen VI related muscular dystrophies (COL6-RD), Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are among the most common congenital muscular dystrophies and are characterized by distal joint laxity and a combination of distal and proximal joint contractures. Inheritance can be dominant negative (DN) or recessive depending on the type and location of the mutation. DN mutations allow incorporation of abnormal chains into secreted tetramers and are the most commonly identified mutation type in COL6-RD. Null alleles (nonsense, frameshift, and large deletions) do not allow incorporation of abnormal chains and act recessively. To better define the pathways disrupted by mutations in collagen VI, we have used a transcriptional profiling approach with RNA-Seq to identify differentially expressed genes in COL6-RD individuals from controls.RNA-Seq allows precise detection of all expressed transcripts in a sample and provides a tool for quantification of expression data on a genomic scale. We have used RNA-Seq to identify differentially expressed genes in cultured dermal fibroblasts from 13 COL6-RD individuals (8 dominant negative and 5 null) and 6 controls. To better assess the transcriptional changes induced by abnormal collagen VI in the extracellular matrix (ECM); we compared transcriptional profiles from subjects with DN mutations and subjects with null mutations to transcriptional profiles from controls.Differentially expressed transcripts between COL6-RD and control fibroblasts include upregulation of ECM components and downregulation of factors controlling matrix remodeling and repair. DN and null samples are differentiated by downregulation of genes involved with DNA replication and repair in null samples.Differentially expressed genes identified here may help identify new targets for development of therapies and biomarkers to assess the efficacy of treatments.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570 ; 572
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Synthetic Oligodeoxynucleotides Containing Multiple Telemeric TTAGGG Motifs Suppress Inflammasome Activity in Macrophages Subjected to Oxygen and Glucose Deprivation and Reduce Ischemic Brain Injury in Stroke-Prone Spontaneously Hypertensive Rats.

    Jing Zhao / Yongshan Mou / Joshua D Bernstock / Dace Klimanis / Sixian Wang / Maria Spatz / Dragan Maric / Kory Johnson / Dennis M Klinman / Xiaohong Li / Xinhui Li / John M Hallenbeck

    PLoS ONE, Vol 10, Iss 10, p e

    2015  Volume 0140772

    Abstract: The immune system plays a fundamental role in both the development and pathobiology of stroke. Inflammasomes are multiprotein complexes that have come to be recognized as critical players in the inflammation that ultimately contributes to stroke severity. ...

    Abstract The immune system plays a fundamental role in both the development and pathobiology of stroke. Inflammasomes are multiprotein complexes that have come to be recognized as critical players in the inflammation that ultimately contributes to stroke severity. Inflammasomes recognize microbial and host-derived danger signals and activate caspase-1, which in turn controls the production of the pro-inflammatory cytokine IL-1β. We have shown that A151, a synthetic oligodeoxynucleotide containing multiple telemeric TTAGGG motifs, reduces IL-1β production by activated bone marrow derived macrophages that have been subjected to oxygen-glucose deprivation and LPS stimulation. Further, we demonstrate that A151 reduces the maturation of caspase-1 and IL-1β, the levels of both the iNOS and NLRP3 proteins, and the depolarization of mitochondrial membrane potential within such cells. In addition, we have demonstrated that A151 reduces ischemic brain damage and NLRP3 mRNA levels in SHR-SP rats that have undergone permanent middle cerebral artery occlusion. These findings clearly suggest that the modulation of inflammasome activity via A151 may contribute to a reduction in pro-inflammatory cytokine production by macrophages subjected to conditions that model brain ischemia and modulate ischemic brain damage in an animal model of stroke. Therefore, modulation of ischemic pathobiology by A151 may have a role in the development of novel stroke prevention and therapeutic strategies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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