Abstract:
:Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be performed or are ineffective. In the past, the stimulation of blood vessel growth was pursued using direct delivery of growth factors, angiogenic gene therapy, or cellular therapy. Although therapeutic angiogenesis holds great promise for treating patients with ischemia, current methods have not found success in clinical trials. Fibroblast growth factor-2 (FGF-2) was one of the first growth factors to be tested for use in therapeutic angiogenesis. Here, we present a method for improving the biological activity of FGF-2 by codelivering the growth factor with a liposomally embedded coreceptor, syndecan-4. This technique was shown to increase FGF-2 cellular signaling, uptake, and nuclear localization in comparison with FGF-2 alone. Delivery of syndecan-4 proteoliposomes also increased endothelial proliferation, migration, and angiogenic tube formation in response to FGF-2. Using an animal model of limb ischemia, syndecan-4 proteoliposomes markedly improved the neovascularization following femoral artery ligation and recovery of perfusion of the ischemic limb. Taken together, these results support liposomal delivery of syndecan-4 as an effective means to improving the potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue.
journal_name
Proc Natl Acad Sci U S Aauthors
Jang E,Albadawi H,Watkins MT,Edelman ER,Baker ABdoi
10.1073/pnas.1117885109subject
Has Abstractpub_date
2012-01-31 00:00:00pages
1679-84issue
5eissn
0027-8424issn
1091-6490pii
1117885109journal_volume
109pub_type
杂志文章abstract::One of the critical issues regarding proteins with a four-helix bundle motif is which interactions play the major role in stabilizing this type of folded structure: the interaction among the four alpha-helices or the interaction between the loop and helix segments. To answer this question, an energetic analysis has be...
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.89.16.7315
更新日期:1992-08-15 00:00:00
abstract::Near infrared diffuse optical spectroscopy and diffuse optical imaging are promising methods that eventually may enhance or replace existing technologies for breast cancer screening and diagnosis. These techniques are based on highly sensitive, quantitative measurements of optical and functional contrast between healt...
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.071511098
更新日期:2001-04-10 00:00:00
abstract::Voltage-dependent anion channels (VDACs) are pore-forming proteins (porins) that form the major pathway for movement of adenine nucleotides through the outer mitochondrial membrane. Electrophysiological studies indicate that VDAC-like channel activity is also prevalent in the cell membranes of many mammalian cells. Ho...
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.060242297
更新日期:2000-03-28 00:00:00
abstract::Both mammals and birds use the interaural time difference (ITD) for localization of sound in the horizontal plane. They may localize either real or phantom sound sources, when the signal consists of a narrow frequency band. This ambiguity does not occur with broadband signals. A plot of impulse rates or amplitude of e...
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.97.22.11787
更新日期:2000-10-24 00:00:00
abstract::In most animals, longevity is achieved at the expense of fertility, but queen honey bees do not show this tradeoff. Queens are both long-lived and fertile, whereas workers, derived from the same genome, are both relatively short-lived and normally sterile. It has been suggested, on the basis of results from workers, 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.0701909104
更新日期:2007-04-24 00:00:00
abstract::Vesicular stomatitis virus (VSV) exhibits a remarkably robust and pantropic infectivity, mediated by its coat protein, VSV-G. Using this property, recombinant forms of VSV and VSV-G-pseudotyped viral vectors are being developed for gene therapy, vaccination, and viral oncolysis and are extensively used for gene transd...
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.1214441110
更新日期:2013-04-30 00:00:00
abstract::Immunological memory is a hallmark of adaptive immunity, and understanding T cell memory will be central to the development of effective cell-mediated vaccines. The characteristics and functions of CD4 memory cells have not been well defined. Here we demonstrate that the increased size of the secondary response is sol...
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.0807449105
更新日期:2008-09-23 00:00:00
abstract::Classification within the genus Pistacia has been based on leaf morphology and geographical distribution. Molecular genetic tools (PCR amplification followed by restriction analysis of a 3.2-kb region of variable chloroplast DNA, and restriction fragment length polymorphism analysis of the Pistacia cpDNA with tobacco ...
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.94.15.7987
更新日期:1997-07-22 00:00:00
abstract::Aerogel materials have myriad scientific and technological applications due to their large intrinsic surface areas and ultralow densities. However, creating a nanodiamond aerogel matrix has remained an outstanding and intriguing challenge. Here we report the high-pressure, high-temperature synthesis of a diamond aerog...
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.1010600108
更新日期:2011-05-24 00:00:00
abstract::Superficial cells from early amphibian embryos display regional specializations of their cell surfaces. That portion of the plasma membrane facing the perivitelline space (apical surface) is nonadhesive, whereas, in the same cell, the lateral and basal portions of the plasma membrane will adhere to other cells. These ...
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.77.6.3460
更新日期:1980-06-01 00:00:00
abstract::Production of reactive oxygen intermediates (ROI) and a form of programmed cell death called hypersensitive response (HR) are often associated with disease resistance of plants. We have previously shown that the Rac homolog of rice, OsRac1, is a regulator of ROI production and cell death in rice. Here we show that 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.021273498
更新日期:2001-01-16 00:00:00
abstract::The impact of rapid climate change on contemporary human populations is of global concern. To contextualize our understanding of human responses to rapid climate change it is necessary to examine the archeological record during past climate transitions. One episode of abrupt climate change has been correlated with soc...
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.1408028111
更新日期:2014-12-02 00:00:00
abstract::Insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute to the development of these disorders, the mo...
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.0402511101
更新日期:2004-07-13 00:00:00
abstract::Many bacterial pathogens of plants and animals have evolved a specialized protein-secretion system termed type III to deliver bacterial proteins into host cells. These proteins stimulate or interfere with host cellular functions for the pathogen's benefit. The Salmonella typhimurium pathogenicity island 1 encodes one ...
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.170128997
更新日期:2000-08-29 00:00:00
abstract::Human settlement of Oceania marked the culmination of a global colonization process that began when humans first left Africa at least 90,000 years ago. The precise origins and dispersal routes of the Austronesian peoples and the associated Lapita culture remain contentious, and numerous disparate models of dispersal (...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.0607753104
更新日期:2007-03-20 00:00:00
abstract::A vestigial, nonphotosynthetic plastid has been identified recently in protozoan parasites of the phylum Apicomplexa. The apicomplexan plastid, or "apicoplast," is indispensable, but the complete sequence of both the Plasmodium falciparum and Toxoplasma gondii apicoplast genomes has offered no clue as to what essentia...
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.95.21.12352
更新日期:1998-10-13 00:00:00
abstract::The synthesis of alpha-chiral amines bearing two alkyl groups has been hampered by the accessibility and stability of the alkylimine precursor. Herein, we report an efficient strategy to generate the alkyl-substituted imine in situ that is compatible with the Me-DuPHOS monoxide.Cu(I) catalyzed addition of diorganozinc...
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.0307096101
更新日期:2004-04-13 00:00:00
abstract::Our previous work [Levinger, L. & Varshavsky, A. (1982) Cell 28, 375-385] has shown that D1, a 50-kilodalton chromosomal protein of Drosophila melanogaster, is specifically associated with isolated nucleosomes that contain a complex A + T-rich satellite DNA with buoyant density of 1.688 g/ml. We show here that D1 is a...
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.79.23.7152
更新日期:1982-12-01 00:00:00
abstract::Molecules of keystone significance are relatively rare, yet mediate a variety of interactions between organisms. They influence the distribution and abundance of species, the transfer of energy across multiple trophic levels, and thus they play significant roles in structuring ecosystems. Despite their potential impor...
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.1103906108
更新日期:2011-07-12 00:00:00
abstract::Acquired resistance to EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inevitable in metastatic EGFR-mutant lung cancers. Here, we modeled disease progression using EGFR-mutant human tumor cell lines. Although five of six models displayed alterations already found in humans, one harbored an unexpected seconda...
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.1203530109
更新日期:2012-07-31 00:00:00
abstract::Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeu...
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.1700694114
更新日期:2017-07-25 00:00:00
abstract::A mutant (ML 308-22) was isolated from Escherichia coli ML 308, which had lost the normal capacity to accumulate lactose analogs despite an increase in the membrane carrier activity. The exit of thiomethylgalactoside was much faster than normal, accounting for the inability of the cell to maintain high intracellular c...
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.65.1.63
更新日期:1970-01-01 00:00:00
abstract::Column chromatography on (dT)(12-18)-cellulose was used to detect and isolate a novel DNA polymerase activity from human breast tumor cell line HBT-3. The new enzyme is similar to those of mammalian RNA tumor viruses in its molecular size, preference for poly(A).(dT)(12-18) as compared to either poly(dA).(dT)(12-18) o...
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.70.8.2453
更新日期:1973-08-01 00:00:00
abstract::Microtubule formation from lamb brain tubulin isolated by affinity chromatography and freed of exchangeable nucleotide requires GTP for maximal rate and extent of polymerization. The nucleotide analogs guanylylmethylenediphosphate and guanylylimidodiphosphate fail to replace GTP; in addition, neither the presence of m...
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.74.2.462
更新日期:1977-02-01 00:00:00
abstract::The effect of 12-O-tetradecanoylphorbol 13-acetate (TPA), a potent tumor promoter, on the synthesis of proteins in BALB/c 3T3 mouse fibroblasts has been studied. When [35S]methionine-labeled proteins synthesized after the addition of TPA were analyzed by one- or two-dimensional polyacrylamide gel electrophoresis, 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.79.6.1800
更新日期:1982-03-01 00:00:00
abstract::Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DN...
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.1519286113
更新日期:2016-03-29 00:00:00
abstract::The MAL6 locus is one of five closely related unlinked loci, any one of which is sufficient for fermentation of maltose in Saccharomyces. Previous genetic analysis indicated that this locus is defined by two complementation groups, MALp and MALg. MALp reportedly is a regulatory gene required for inducible synthesis of...
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.81.9.2811
更新日期:1984-05-01 00:00:00
abstract::Glucocorticoids (GCs) are potent anti-inflammatory agents that block cytokine production. We investigated whether GCs also block cytokine signaling via the Janus kinase (Jak)-signal transducer and activator of transcription (STAT) pathway. Dexamethasone inhibited IL-2-induced DNA binding, tyrosine phosphorylation, and...
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.160099797
更新日期:2000-08-15 00:00:00
abstract::The chimaeric protein repressor-galactosidase, in which fully active lac repressor is covalently linked to the active enzyme beta-galactosidase, was used as a system for probing the quaternary structure of lac repressor. Electron micrographs revealed repressor-galactosidase to be a tetrameric aggregate. When lac repre...
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.73.10.3529
更新日期:1976-10-01 00:00:00
abstract::Amnesia produced by protein synthesis inhibitors such as anisomycin provides major support for the prevalent view that the formation of long-lasting memories requires de novo protein synthesis. However, inhibition of protein synthesis might disrupt other neural functions to interfere with memory formation. Intraamygda...
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.0705195104
更新日期:2007-07-24 00:00:00