Abstract:
:Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9-T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI.
journal_name
Proc Natl Acad Sci U S Aauthors
Ropper AE,Thakor DK,Han I,Yu D,Zeng X,Anderson JE,Aljuboori Z,Kim SW,Wang H,Sidman RL,Zafonte RD,Teng YDdoi
10.1073/pnas.1616340114subject
Has Abstractpub_date
2017-01-31 00:00:00pages
E820-E829issue
5eissn
0027-8424issn
1091-6490pii
1616340114journal_volume
114pub_type
杂志文章abstract::Mutations in the visA gene of Escherichia coli cause the mutant bacteria to die upon illumination with visible light. We confirmed genetically that the visA gene is a structural gene for ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1). Since other mutations in the genes involved in the biosynthesis of heme can cur...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.23.10520
更新日期:1991-12-01 00:00:00
abstract::The "WD40" domain is a widespread recognition module for linking partner proteins in intracellular networks of signaling and sorting. The clathrin amino-terminal domain, which directs incorporation of cargo into coated pits, is a beta-propeller closely related in structure to WD40 modules. The crystallographically det...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::The tissue-specific, cell-aggregating component of embryonic neural retina cells was purified from the retina cell-aggregating factor and characterized as a glycoprotein. Its molecular weight in solution is in the range of 50,000, and it contains 10-15% carbohydrate. The amino-acid and carbohydrate compositions have b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.3.916
更新日期:1975-03-01 00:00:00
abstract::Cavitation, known as the formation of vapor bubbles when liquids are under tension, is of great interest both in condensed matter science as well as in diverse applications such as botany, hydraulic engineering, and medicine. Although widely studied in bulk and microscale-confined liquids, cavitation in the nanoscale ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1014075109
更新日期:2012-03-06 00:00:00
abstract::We sequenced the genome of Saccharomyces cerevisiae strain YJM789, which was derived from a yeast isolated from the lung of an AIDS patient with pneumonia. The strain is used for studies of fungal infections and quantitative genetics because of its extensive phenotypic differences to the laboratory reference strain, i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0701291104
更新日期:2007-07-31 00:00:00
abstract::PDZ domains are abundant protein interaction modules and typically recognize a short motif at the C terminus of their ligands, with a few residues in the motif endowing the binding specificity. The sequence-based rules, however, cannot fully account for the specificity between the vast number of PDZ domains and ligand...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1508931112
更新日期:2015-12-01 00:00:00
abstract::Most neurotransmission is mediated by action potentials, whereas sensory neurons propagate electrical signals passively and release neurotransmitter in a graded manner. Here, we demonstrate that Caenorhabditis elegans neuromuscular junctions release neurotransmitter in a graded fashion. When motor neurons were depolar...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0903570106
更新日期:2009-06-30 00:00:00
abstract::Graphene superlattices were shown to exhibit high-temperature quantum oscillations due to periodic emergence of delocalized Bloch states in high magnetic fields such that unit fractions of the flux quantum pierce a superlattice unit cell. Under these conditions, semiclassical electron trajectories become straight agai...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1804572115
更新日期:2018-05-15 00:00:00
abstract::Helix-hairpin-helix DNA glycosylases are typically small proteins that initiate repair of DNA by excising damaged or mispaired bases. An invariant aspartic acid in the active site is involved in catalyzing the excision reaction. Replacement of this critical residue with an asparagine severely reduces catalytic activit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402328101
更新日期:2004-05-11 00:00:00
abstract::The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0236849100
更新日期:2003-01-21 00:00:00
abstract::Regulation of IFN signaling is critical in host recognition and response to pathogens while its dysregulation underlies the pathogenesis of several chronic diseases. STimulator of IFN Genes (STING) has been identified as a critical mediator of IFN inducing innate immune pathways, but little is known about direct coreg...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1901090116
更新日期:2019-08-13 00:00:00
abstract::Although many types of ancient bacteria and archea rely on hydrogen sulfide (H(2)S) for their energy production, eukaryotes generate ATP in an oxygen-dependent fashion. We hypothesize that endogenous H(2)S remains a regulator of energy production in mammalian cells under stress conditions, which enables the body to co...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1115634109
更新日期:2012-02-21 00:00:00
abstract::Understanding modulation of memory, as well as the mechanisms underlying memory formation, has become a key issue in neuroscience research. Previously, we found that the formation of long-term, but not short-term, memory for a nonassociative form of learning, sensitization, was modulated by the circadian clock in the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0503847102
更新日期:2005-08-30 00:00:00
abstract::T cells that have been immunized to express optimal levels of contact hypersensitivity upon adoptive transfer to normal animals can be inhibited from doing so by incubating them with an antigen-specific T suppressor factor. This factor is composed of at least two subunits which come from cells expressing different Ly ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.7.2375
更新日期:1982-04-01 00:00:00
abstract::Initiation of adenovirus DNA replication in vitro occurs on a linearized plasmid DNA containing 3,327 base pairs of the adenovirus terminal sequence. Various deletions have been constructed in the plasmid DNA and their template activities examined. Deletions from an internal restriction enzyme cleavage site that retai...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.21.6446
更新日期:1983-11-01 00:00:00
abstract::Past research found that the ingestion of glucose can enhance self-control. It has been widely assumed that basic physiological processes underlie this effect. We hypothesized that the effect of glucose also depends on people's theories about willpower. Three experiments, both measuring (experiment 1) and manipulating...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1313475110
更新日期:2013-09-10 00:00:00
abstract::All proteins of this world are constructed in compliance with the same rule. Accordingly, two totally unrelated proteins, on the average, share 30 identical tripeptides, two tetrapeptides, and one pentapeptide per 500 residues. With this in mind, the 221-residue-long influenza virus hemagglutinin II (IVHA-II), as a re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.8.3065
更新日期:1991-04-15 00:00:00
abstract::Thymidine kinase-deficient mouse L cells have been transformed with plasmid DNAs carrying 8-base-pair Xho I linker insertion mutations in the coding region of the herpes simplex virus type 1 thymidine kinase gene. When the mutant plasmids are introduced individually into LTK- cells, transformation efficiencies are gre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.15.4827
更新日期:1983-08-01 00:00:00
abstract::P/Q Ca(2+) channel activity is inhibited by G protein-coupled receptor activation. Channel inhibition requires a direct Gbetagamma binding onto the pore-forming subunit, Ca(v)2.1. It is characterized by biophysical changes, including current amplitude reduction, activation kinetic slowing, and an I-V curve shift, whic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0306804101
更新日期:2004-04-20 00:00:00
abstract::The endometrial epithelium of the uterus regenerates periodically. The cellular source of newly regenerated endometrial epithelia during a mouse estrous cycle or a human menstrual cycle is presently unknown. Here, I have used single-cell lineage tracing in the whole mouse uterus to demonstrate that epithelial stem cel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1814597116
更新日期:2019-04-02 00:00:00
abstract::Our ability to interpret seismic observations including the seismic discontinuities and the density and velocity profiles in the earth's interior is critically dependent on the accuracy of pressure measurements up to 364 GPa at high temperature. Pressure scales based on the reduced shock-wave equations of state alone ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0609013104
更新日期:2007-05-29 00:00:00
abstract::Metals in one spatial dimension are described at the lowest energy scales by the Luttinger liquid theory. It is well understood that this free theory, and even interacting integrable models, can support ballistic transport of conserved quantities including energy. In contrast, realistic one-dimensional metals, even wi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1916213117
更新日期:2020-06-09 00:00:00
abstract::Myocardin and the myocardin-related transcription factors (MRTFs) A and B act as coactivators for serum response factor, which plays a key role in cardiovascular development. To determine the functions of MRTF-B in vivo, we generated MRTF-B mutant mice by targeted inactivation of the MRTF-B gene. We show that mice hom...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0507346102
更新日期:2005-10-18 00:00:00
abstract::The sterol regulatory element-binding protein (SREBP) family of transcription factors controls the biosynthesis of cholesterol and other lipids, and lipid synthesis is critical for cell growth and proliferation. We were, therefore, interested in the expression and activity of SREBPs during the cell cycle. We found tha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0501494102
更新日期:2005-08-16 00:00:00
abstract::We present the discovery of an unusually large isotope effect in the structural relaxation and the glass transition temperature Tg of water. Dielectric relaxation spectroscopy of low-density as well as of vapor-deposited amorphous water reveal Tg differences of 10 ± 2 K between H2O and D2O, sharply contrasting with ot...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1411620111
更新日期:2014-12-09 00:00:00
abstract::We applied the directional tag PCR subtractive hybridization method to construct a rat hypothalamic cDNA library from which cerebellar and hippocampal sequences had been depleted, enriching 20-30-fold for sequences expressed selectively in the hypothalamus. We studied a sample of 94 clones selected for enrichment in t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.16.8733
更新日期:1996-08-06 00:00:00
abstract::Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1008950108
更新日期:2011-01-04 00:00:00
abstract::We investigated the possibility of positive selection acting on members of the putative seven-pass chemoreceptor superfamily in Caenorhabditis elegans, which comprises approximately 1,300 genes encoding seven-pass G protein-coupled receptors (GPCRs). Using a maximum-likelihood approach, we conducted statistical tests ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0406469102
更新日期:2005-03-22 00:00:00
abstract::The peripheral axonal branch of primary sensory neurons readily regenerates after peripheral nerve injury, but the central branch, which courses in the dorsal columns of the spinal cord, does not. However, if a peripheral nerve is transected before a spinal cord injury, sensory neurons that course in the dorsal column...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0508538102
更新日期:2005-11-15 00:00:00
abstract::Endogenous retroviruses (ERVs) are the remnants of ancient retroviral infections of germ cells and have been maintained in whole or part as heritable genomic elements. The last known endogenization events occurred several million years ago, and therefore stepwise analysis of retroviral endogenization has not been poss...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0704313104
更新日期:2007-10-30 00:00:00