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Article ; Online: Linking connectome with transcriptome using a self-inactivating rabies virus.

Yao, Shenqin / Levi, Boaz P

2023 Volume 20, Issue 4, Page(s) 493–494

MeSH term(s)	Rabies virus/genetics ; Connectome ; Transcriptome ; Antibodies, Viral
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-03-02
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2169522-2
ISSN	1548-7105 ; 1548-7091
ISSN (online)	1548-7105
ISSN	1548-7091
DOI	10.1038/s41592-023-01803-4
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Article ; Online: Putting Two Heads Together to Build a Better Brain.

Mich, John K / Close, Jennie L / Levi, Boaz P

Cell stem cell

2017 Volume 21, Issue 3, Page(s) 289–290

Abstract: 3D organoids enable in vitro human brain development models, but they have not yet recapitulated some essential features of brain circuit formation. Recently, several studies appearing in Nature, Nature Methods, and Cell Stem Cell generated fused ... ...

Abstract	3D organoids enable in vitro human brain development models, but they have not yet recapitulated some essential features of brain circuit formation. Recently, several studies appearing in Nature, Nature Methods, and Cell Stem Cell generated fused organoid models of inhibitory and excitatory neuron development, which can now achieve functional circuit integration.
MeSH term(s)	Brain ; Cell Movement ; Humans ; Interneurons ; Neurogenesis ; Organoids
Language	English
Publishing date	2017-09-08
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2017.08.017
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Article: AAV-mediated interneuron-specific gene replacement for Dravet syndrome.

Mich, John K / Ryu, Jiyun / Wei, Aguan D / Gore, Bryan B / Guo, Rong / Bard, Angela M / Martinez, Refugio A / Bishaw, Yemeserach / Luber, Em / Oliveira Santos, Luiz M / Miranda, Nicole / Ramirez, Jan-Marino / Ting, Jonathan T / Lein, Ed S / Levi, Boaz P / Kalume, Franck K

bioRxiv : the preprint server for biology

2023

Abstract: Dravet syndrome (DS) is a devastating developmental epileptic encephalopathy marked by treatment-resistant seizures, developmental delay, intellectual disability, motor deficits, and a 10-20% rate of premature death. Most DS patients harbor loss-of- ... ...

Abstract	Dravet syndrome (DS) is a devastating developmental epileptic encephalopathy marked by treatment-resistant seizures, developmental delay, intellectual disability, motor deficits, and a 10-20% rate of premature death. Most DS patients harbor loss-of-function mutations in one copy of
Language	English
Publishing date	2023-12-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.15.571820
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Article ; Online: Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons.

Matson, Kaya J E / Russ, Daniel E / Kathe, Claudia / Hua, Isabelle / Maric, Dragan / Ding, Yi / Krynitsky, Jonathan / Pursley, Randall / Sathyamurthy, Anupama / Squair, Jordan W / Levi, Boaz P / Courtine, Gregoire / Levine, Ariel J

Nature communications

2022 Volume 13, Issue 1, Page(s) 5628

Abstract: After spinal cord injury, tissue distal to the lesion contains undamaged cells that could support or augment recovery. Targeting these cells requires a clearer understanding of their injury responses and capacity for repair. Here, we use single nucleus ... ...

Abstract	After spinal cord injury, tissue distal to the lesion contains undamaged cells that could support or augment recovery. Targeting these cells requires a clearer understanding of their injury responses and capacity for repair. Here, we use single nucleus RNA sequencing to profile how each cell type in the lumbar spinal cord changes after a thoracic injury in mice. We present an atlas of these dynamic responses across dozens of cell types in the acute, subacute, and chronically injured spinal cord. Using this resource, we find rare spinal neurons that express a signature of regeneration in response to injury, including a major population that represent spinocerebellar projection neurons. We characterize these cells anatomically and observed axonal sparing, outgrowth, and remodeling in the spinal cord and cerebellum. Together, this work provides a key resource for studying cellular responses to injury and uncovers the spontaneous plasticity of spinocerebellar neurons, uncovering a potential candidate for targeted therapy.
MeSH term(s)	Animals ; Axons/metabolism ; Cerebellum/metabolism ; Mice ; Nerve Regeneration/physiology ; Neurons/metabolism ; Spinal Cord/metabolism ; Spinal Cord Injuries/pathology
Language	English
Publishing date	2022-09-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-33184-1
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Article ; Online: A systematic screen for tube morphogenesis and branching genes in the Drosophila tracheal system.

Ghabrial, Amin S / Levi, Boaz P / Krasnow, Mark A

PLoS genetics

2011 Volume 7, Issue 7, Page(s) e1002087

Abstract: Many signaling proteins and transcription factors that induce and pattern organs have been identified, but relatively few of the downstream effectors that execute morphogenesis programs. Because such morphogenesis genes may function in many organs and ... ...

Abstract	Many signaling proteins and transcription factors that induce and pattern organs have been identified, but relatively few of the downstream effectors that execute morphogenesis programs. Because such morphogenesis genes may function in many organs and developmental processes, mutations in them are expected to be pleiotropic and hence ignored or discarded in most standard genetic screens. Here we describe a systematic screen designed to identify all Drosophila third chromosome genes (∼40% of the genome) that function in development of the tracheal system, a tubular respiratory organ that provides a paradigm for branching morphogenesis. To identify potentially pleiotropic morphogenesis genes, the screen included analysis of marked clones of homozygous mutant tracheal cells in heterozygous animals, plus a secondary screen to exclude mutations in general "house-keeping" genes. From a collection including more than 5,000 lethal mutations, we identified 133 mutations representing ∼70 or more genes that subdivide the tracheal terminal branching program into six genetically separable steps, a previously established cell specification step plus five major morphogenesis and maturation steps: branching, growth, tubulogenesis, gas-filling, and maintenance. Molecular identification of 14 of the 70 genes demonstrates that they include six previously known tracheal genes, each with a novel function revealed by clonal analysis, and two well-known growth suppressors that establish an integral role for cell growth control in branching morphogenesis. The rest are new tracheal genes that function in morphogenesis and maturation, many through cytoskeletal and secretory pathways. The results suggest systematic genetic screens that include clonal analysis can elucidate the full organogenesis program and that over 200 patterning and morphogenesis genes are required to build even a relatively simple organ such as the Drosophila tracheal system.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/growth & development ; Gene Expression Regulation, Developmental ; Genes, Insect ; Genes, Lethal ; Heterozygote ; Homozygote ; Morphogenesis ; Mutation ; Trachea/growth & development ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Drosophila Proteins ; Transcription Factors
Language	English
Publishing date	2011-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1002087
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Article ; Online: Integrating physiological regulation with stem cell and tissue homeostasis.

Nakada, Daisuke / Levi, Boaz P / Morrison, Sean J

Neuron

2011 Volume 70, Issue 4, Page(s) 703–718

Abstract: Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from ... ...

Abstract	Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation, also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology.
MeSH term(s)	Animals ; Cell Differentiation/physiology ; Cell Proliferation ; Guided Tissue Regeneration/methods ; Homeostasis/physiology ; Humans ; Nerve Net/cytology ; Nerve Net/physiology ; Signal Transduction/physiology ; Stem Cells/cytology ; Stem Cells/physiology
Language	English
Publishing date	2011-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2011.05.011
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.

Chen, Xinhong / Wolfe, Damien A / Bindu, Dhanesh Sivadasan / Zhang, Mengying / Taskin, Naz / Goertsen, David / Shay, Timothy F / Sullivan, Erin E / Huang, Sheng-Fu / Ravindra Kumar, Sripriya / Arokiaraj, Cynthia M / Plattner, Viktor M / Campos, Lillian J / Mich, John K / Monet, Deja / Ngo, Victoria / Ding, Xiaozhe / Omstead, Victoria / Weed, Natalie /

Bishaw, Yeme / Gore, Bryan B / Lein, Ed S / Akrami, Athena / Miller, Cory / Levi, Boaz P / Keller, Annika / Ting, Jonathan T / Fox, Andrew S / Eroglu, Cagla / Gradinaru, Viviana

Nature communications

2023 Volume 14, Issue 1, Page(s) 3345

Abstract: Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain ... ...

Abstract	Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits.
MeSH term(s)	Mice ; Rats ; Animals ; Endothelial Cells/metabolism ; Rodentia/genetics ; Macaca mulatta/genetics ; Brain/metabolism ; Tropism/genetics ; Mice, Knockout ; Dependovirus/metabolism ; Genetic Vectors/genetics ; Transduction, Genetic ; Calcium-Binding Proteins/metabolism ; Extracellular Matrix Proteins/genetics
Chemical Substances	Sparcl1 protein, mouse ; Calcium-Binding Proteins ; Extracellular Matrix Proteins
Language	English
Publishing date	2023-06-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-38582-7
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Article ; Online: Interindividual variation in human cortical cell type abundance and expression.

Johansen, Nelson / Somasundaram, Saroja / Travaglini, Kyle J / Yanny, Anna Marie / Shumyatcher, Maya / Casper, Tamara / Cobbs, Charles / Dee, Nick / Ellenbogen, Richard / Ferreira, Manuel / Goldy, Jeff / Guzman, Junitta / Gwinn, Ryder / Hirschstein, Daniel / Jorstad, Nikolas L / Keene, C Dirk / Ko, Andrew / Levi, Boaz P / Ojemann, Jeffrey G /

Pham, Thanh / Shapovalova, Nadiya / Silbergeld, Daniel / Sulc, Josef / Torkelson, Amy / Tung, Herman / Smith, Kimberly / Lein, Ed S / Bakken, Trygve E / Hodge, Rebecca D / Miller, Jeremy A

Science (New York, N.Y.)

2023 Volume 382, Issue 6667, Page(s) eadf2359

Abstract: Single-cell transcriptomic studies have identified a conserved set of neocortical cell types from small postmortem cohorts. We extended these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. ... ...

Abstract	Single-cell transcriptomic studies have identified a conserved set of neocortical cell types from small postmortem cohorts. We extended these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one of 125 robust cell types identified in the middle temporal gyrus. However, we found interindividual variance in abundances and gene expression signatures, particularly in deep-layer glutamatergic neurons and microglia. A minority of donor variance is explainable by age, sex, ancestry, disease state, and cell state. Genomic variation was associated with expression of 150 to 250 genes for most cell types. This characterization of cellular variation provides a baseline for cell typing in health and disease.
MeSH term(s)	Adult ; Humans ; Epilepsy/metabolism ; Gene Expression Profiling ; Neurons/metabolism ; Temporal Lobe/cytology ; Temporal Lobe/metabolism ; Transcriptome ; Nervous System Diseases/genetics ; Mental Disorders/genetics
Language	English
Publishing date	2023-10-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adf2359
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain.

Chuapoco, Miguel R / Flytzanis, Nicholas C / Goeden, Nick / Christopher Octeau, J / Roxas, Kristina M / Chan, Ken Y / Scherrer, Jon / Winchester, Janet / Blackburn, Roy J / Campos, Lillian J / Man, Kwun Nok Mimi / Sun, Junqing / Chen, Xinhong / Lefevre, Arthur / Singh, Vikram Pal / Arokiaraj, Cynthia M / Shay, Timothy F / Vendemiatti, Julia / Jang, Min J /

Mich, John K / Bishaw, Yemeserach / Gore, Bryan B / Omstead, Victoria / Taskin, Naz / Weed, Natalie / Levi, Boaz P / Ting, Jonathan T / Miller, Cory T / Deverman, Benjamin E / Pickel, James / Tian, Lin / Fox, Andrew S / Gradinaru, Viviana

Nature nanotechnology

2023 Volume 18, Issue 10, Page(s) 1241–1251

Abstract: Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic ... ...

Abstract	Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates. Here we report on AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques, which has improved delivery efficiency in the brains of multiple non-human primate species: marmoset, rhesus macaque and green monkey. CAP-Mac is neuron biased in infant Old World primates, exhibits broad tropism in adult rhesus macaques and is vasculature biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver functional GCaMP for ex vivo calcium imaging across multiple brain areas, or a cocktail of fluorescent reporters for Brainbow-like labelling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. As such, CAP-Mac is shown to have potential for non-invasive systemic gene transfer in the brains of non-human primates.
MeSH term(s)	Humans ; Animals ; Infant, Newborn ; Chlorocebus aethiops ; Macaca mulatta/genetics ; Callithrix/genetics ; Brain/physiology ; Gene Transfer Techniques ; Neurons ; Genetic Vectors/genetics
Language	English
Publishing date	2023-07-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2254964-X
ISSN	1748-3395 ; 1748-3387
ISSN (online)	1748-3395
ISSN	1748-3387
DOI	10.1038/s41565-023-01419-x
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Article: Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.

Chen, Xinhong / Wolfe, Damien A / Bindu, Dhanesh Sivadasan / Zhang, Mengying / Taskin, Naz / Goertsen, David / Shay, Timothy F / Sullivan, Erin / Huang, Sheng-Fu / Kumar, Sripriya Ravindra / Arokiaraj, Cynthia M / Plattner, Viktor / Campos, Lillian J / Mich, John / Monet, Deja / Ngo, Victoria / Ding, Xiaozhe / Omstead, Victoria / Weed, Natalie /

Bishaw, Yeme / Gore, Bryan / Lein, Ed S / Akrami, Athena / Miller, Cory / Levi, Boaz P / Keller, Annika / Ting, Jonathan T / Fox, Andrew S / Eroglu, Cagla / Gradinaru, Viviana

bioRxiv : the preprint server for biology

2023

Abstract	Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds and rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and
Language	English
Publishing date	2023-01-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.12.523844
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