Abstract:
:Small molecules produced by Actinobacteria have played a prominent role in both drug discovery and organic chemistry. As part of a larger study of the actinobacterial symbionts of fungus-growing ants, we discovered a small family of three previously unreported piperazic acid-containing cyclic depsipeptides, gerumycins A-C. The gerumycins are slightly smaller versions of dentigerumycin, a cyclic depsipeptide that selectively inhibits a common fungal pathogen, Escovopsis. We had previously identified this molecule from a Pseudonocardia associated with Apterostigma dentigerum, and now we report the molecule from an associate of the more highly derived ant Trachymyrmex cornetzi. The three previously unidentified compounds, gerumycins A-C, have essentially identical structures and were produced by two different symbiotic Pseudonocardia spp. from ants in the genus Apterostigma found in both Panama and Costa Rica. To understand the similarities and differences in the biosynthetic pathways that produced these closely related molecules, the genomes of the three producing Pseudonocardia were sequenced and the biosynthetic gene clusters identified. This analysis revealed that dramatically different biosynthetic architectures, including genomic islands, a plasmid, and the use of spatially separated genetic loci, can lead to molecules with virtually identical core structures. A plausible evolutionary model that unifies these disparate architectures is presented.
journal_name
Proc Natl Acad Sci U S Aauthors
Sit CS,Ruzzini AC,Van Arnam EB,Ramadhar TR,Currie CR,Clardy Jdoi
10.1073/pnas.1515348112subject
Has Abstractpub_date
2015-10-27 00:00:00pages
13150-4issue
43eissn
0027-8424issn
1091-6490pii
1515348112journal_volume
112pub_type
杂志文章abstract::Cell mechanics plays a role in stem cell reprogramming and differentiation. To understand this process better, we created a genetically encoded optical probe, named actin-cpstFRET-actin (AcpA), to report forces in actin in living cells in real time. We showed that stemness was associated with increased force in actin....
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.1411683111
更新日期:2014-12-09 00:00:00
abstract::Measles still remains a major cause of childhood morbidity and mortality worldwide. Measles virus (MV) vaccines are highly successful, but the mechanism underlying their efficacy has been unclear. Here we report the crystal structure of the MV attachment protein, hemagglutinin, responsible for MV entry. The receptor-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.0707830104
更新日期:2007-12-04 00:00:00
abstract::Mouse interferon preparations inhibited the multiplication of mouse leukemia L 1210 cells cultivated under steady-state conditions in a chemostat. The use of this sensitive and controlled system led to the detection of a rapid inhibition in the incorporation of (3-H)thymidine into cellular acid-precipitable material 2...
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.72.6.2265
更新日期:1975-06-01 00:00:00
abstract::Landscape-scale reconstructions of ancient environments within the cradle of humanity may reveal insights into the relationship between early hominins and the changing resources around them. Many studies of Olduvai Gorge during Pliocene-Pleistocene times have revealed the presence of precession-driven wet-dry cycles 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.2004532117
更新日期:2020-10-06 00:00:00
abstract::Because most human squamous carcinoma cell lines of the aerodigestive and genital tracts are refractory to the antiproliferative action of transforming growth factor beta 1 (TGF beta 1) in vitro, we have begun to identify the causes for resistance of squamous carcinoma cell lines to TGF beta 1 by using somatic cell ge...
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.90.13.6280
更新日期:1993-07-01 00:00:00
abstract::The 33-amino-acid ankyrin motif comprises a beta-turn followed by two anti-parallel alpha-helices and a loop and tandem arrays of the motif pack in a linear fashion to produce elongated structures characterized by short-range interactions. In this article we use site-directed mutagenesis to investigate the kinetic unf...
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.0705300105
更新日期:2008-07-22 00:00:00
abstract::The genome of the defective avian tumor virus MH2 was identified as a RNA of 5.7 kilobases by its presence in different MH2-helper virus complexes and its absence from pure helper virus, by its unique fingerprint pattern of RNase T1-resistant (T1) oligonucleotides that differed from those of two helper virus RNAs, 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.76.4.1633
更新日期:1979-04-01 00:00:00
abstract::Papain solubilized H-2a histocompatibility antigens (H-2Kk plus H-2Dd) have been purified by a large-scale procedure that can routinely provide 2-3 mg of heavy chain from 1 kg of mouse liver. The heavy chains were homogeneous by sodium dodecyl sulfate electrophoresis. Disc gel electrophoresis resolved two protein band...
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.75.7.3322
更新日期:1978-07-01 00:00:00
abstract::A yeast gene has been identified by screening for DNA replication mutants using a permeabilized cell replication assay. The mutant is temperature sensitive for growth and shows a cell cycle phenotype typical of DNA replication mutants. RNA synthesis is normal in the mutant but DNA synthesis ceases upon shift to the no...
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.92.17.7642
更新日期:1995-08-15 00:00:00
abstract::We established a pancreatic adenocarcinoma cell line (CFPAC-1) from a patient with cystic fibrosis (CF) and assessed some of its properties. The cells show epithelial morphology and express cytokeratin and oncofetal antigens characteristic of pancreatic duct cells. Basal and stimulated levels of cAMP and cAMP-dependen...
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.87.10.4012
更新日期:1990-05-01 00:00:00
abstract::Tyrosine hydroxylase (EC 1.14.16.2), the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis, was localized by electron microscopy within noradrenergic neurons of the nucleus locus coeruleus of the rat brain with a specific antibody to tyrosine hydroxylase labeled by the peroxidase-antiperoxidase im...
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.72.2.659
更新日期:1975-02-01 00:00:00
abstract::Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their charac...
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.1901169116
更新日期:2019-08-27 00:00:00
abstract::A varying oxygen environment is known to affect cellular function in disease as well as activity of various therapeutics. For transient structures, whether they are unconstrained therapeutic transplants, migrating cells during tumor metastasis, or cell populations induced by an immunological response, the role of oxyg...
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.1815909116
更新日期:2019-03-12 00:00:00
abstract::Neuropathogenicity of poliovirus can be attenuated by mutations in the internal ribosomal entry site (IRES) within the 5' nontranslated region of its genome. The Sabin vaccine strains used in prevention of poliomyelitis carry such mutations in their IRES elements. In addition, mutations within the structural and nonst...
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.93.6.2370
更新日期:1996-03-19 00:00:00
abstract::Endothelial cell growth factor (ECGF) binds specifically in vitro to membrane receptors present on the surface of several cell types, including murine and human endothelial cells and fibroblasts. Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor prevent receptor occup...
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.82.18.6138
更新日期:1985-09-01 00:00:00
abstract::Meiosis-specific homologs of RecA protein have been identified in Saccharomyces cerevisiae and higher eukaryotes including mammals, but their enzymatic activities have not been described. We have purified the human protein HsDmc1 produced in Escherichia coli from a cloned copy of the cDNA. The recombinant enzyme had D...
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.94.21.11221
更新日期:1997-10-14 00:00:00
abstract::Susceptibility of activated T cells to apoptosis must be tightly regulated to ensure sufficient T cell progeny for an effective response, while allowing a rapid depletion of them at the end of the immune response. We show here that a previously isolated, NF-kappa B/rel target gene IEX-1 (Immediate Early response gene ...
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.022326699
更新日期:2002-01-22 00:00:00
abstract::Nonhuman primates possess a highly developed capacity for face recognition, which resembles the human capacity both cognitively and neurologically. Face recognition is typically tested by having subjects compare facial images, whereas there has been virtually no attention to how they connect these images to reality. 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.0912174106
更新日期:2009-12-22 00:00:00
abstract::Transthyretin (TTR) is a globular tetrameric transport protein in plasma. Nearly 140 single amino acid substitutions in TTR cause life-threatening amyloid disease. We report a one-of-a-kind pathological variant featuring a Glu51, Ser52 duplication mutation (Glu51_Ser52dup). The proband, heterozygous for the mutation, ...
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.1802977115
更新日期:2018-07-10 00:00:00
abstract::The modern Old World Monkeys (Superfamily Cercopithecoidea, Family Cercopithecidae) can be traced back into the late Miocene, but their origin and subsequent diversification is obscured by the scarcity of terrestrial fossil sites in Africa between 15 and 6 Ma. Here, we document the presence of cercopithecids at 12.5 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.1213691110
更新日期:2013-04-09 00:00:00
abstract::We have previously shown that lymphoblasts alloactivated in vitro acquire the capacity of stimulating the autologous mixed lymphocyte response. This response is anti-idiotypic in nature because lymphocytes so primed display accelerated memory responses only when restimulated by autologous lymphoblasts that have been 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.80.3.830
更新日期:1983-02-01 00:00:00
abstract::Mutations in copper/zinc superoxide dismutase (SOD1) are causative for dominantly inherited amyotrophic lateral sclerosis (ALS). Despite high variability in biochemical properties among the disease-causing mutants, a proportion of both dismutase-active and -inactive mutants are stably bound to spinal cord mitochondria...
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.0712209105
更新日期:2008-03-11 00:00:00
abstract::How subduction-the sinking of cold lithospheric plates into the mantle-is initiated is one of the key mysteries in understanding why Earth has plate tectonics. One of the favored locations for subduction triggering is at passive margins, where sea floor abuts continental margins. Such passive margin collapse is proble...
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.2011247118
更新日期:2021-01-26 00:00:00
abstract::We have earlier reported conditions that support the axenic development in vitro of a complete asexual erythrocytic cycle of Plasmodium falciparum. Up to 30% of merozoites showed initial differentiation into trophic forms (rings) viable at 14 hr. However, only approximately 1% of the merozoites would develop further 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.92.2.566
更新日期:1995-01-17 00:00:00
abstract::The expression of interleukin-4 (IL-4) is viewed as the hallmark of a Th2 lymphocyte, whereas the subsequent action of IL-4 and IL-13, mediated through the STAT6 signaling pathway, is seen as a prerequisite for the full development of Th2 immune responses to parasites and allergens. G4 mice, whose IL-4 gene locus cont...
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.0806372105
更新日期:2008-08-26 00:00:00
abstract::Organ graft rejection is a T-cell-dependent process. The activation of alloreactive T cells requires stimulation of the T-cell receptor/CD3 complex by foreign major histocompatibility complex (MHC)-encoded gene products. However, accumulating evidence suggests that, in addition to T-cell receptor occupancy, other cost...
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.89.22.11102
更新日期:1992-11-15 00:00:00
abstract::Gene knockout is the most powerful tool for determining gene function or permanently modifying the phenotypic characteristics of a cell. Existing methods for gene disruption are limited by their efficiency, time to completion, and/or the potential for confounding off-target effects. Here, we demonstrate a rapid single...
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.0800940105
更新日期:2008-04-15 00:00:00
abstract::Argonaute (Ago) proteins are the key component of the RNA-induced silencing complex and mediate RNA interference (RNAi) in association with small RNAs. Although overall the mechanism of RNAi is well understood, many molecular details of this complex process are not. Here we report about in-depth steady-state and, in p...
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.1217838110
更新日期:2013-10-29 00:00:00
abstract::Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, and ultimately insulin resistance. We hypothesized that VEGF-A-induced stimulation of angiogenesis enables sustained and sufficient oxygen and nutrient exchange during fat mass expansion, thereby improving adipose...
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.1200447109
更新日期:2012-04-10 00:00:00
abstract::The NIFA protein of Klebsiella pneumoniae is required for transcription of all nif (nitrogen fixation) operons except the regulatory nifLA operon itself. NIFA activates transcription of nif operons by the alternative holoenzyme form of RNA polymerase, sigma 54-holoenzyme, in a nucleoside triphosphate (NTP)-dependent 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.91.1.103
更新日期:1994-01-04 00:00:00