Abstract:
:Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung progenitor cells, the identity of molecules that might be therapeutically targeted in response to infections to promote activation of progenitor cell types remains elusive. Here, we report that loss of Abl1 specifically in SCGB1A1-expressing cells leads to a significant increase in the proliferation and differentiation of bronchiolar epithelial cells, resulting in dramatic expansion of an SCGB1A1+ airway cell population that coexpresses SPC, a marker for type II alveolar cells that promotes alveolar regeneration following bacterial pneumonia. Furthermore, treatment with an Abl-specific allosteric inhibitor enhanced regeneration of the alveolar epithelium and promoted accelerated recovery of mice following pneumonia. These data reveal a potential actionable target that may be exploited for efficient recovery after pathogen-induced infections.
journal_name
Proc Natl Acad Sci U S Aauthors
Khatri A,Kraft BD,Tata PR,Randell SH,Piantadosi CA,Pendergast AMdoi
10.1073/pnas.1816030116subject
Has Abstractpub_date
2019-01-29 00:00:00pages
1603-1612issue
5eissn
0027-8424issn
1091-6490pii
1816030116journal_volume
116pub_type
杂志文章abstract::By employing the nuclear DNA of the African rice Oryza glaberrima as a reference genome, the timing, natures, mechanisms, and specificities of recent sequence evolution in the indica and japonica subspecies of Oryza sativa were identified. The data indicate that the genome sizes of both indica and japonica have increa...
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.0403715101
更新日期:2004-08-24 00:00:00
abstract::The caspases are cysteine proteases that have been implicated in the execution of programmed cell death in organisms ranging from nematodes to humans. Many members of the Bcl-2 family, including Bcl-XL, are potent inhibitors of programmed cell death and inhibit activation of caspases in cells. Here, we report a direct...
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.95.2.554
更新日期:1998-01-20 00:00:00
abstract::Understanding how electric fields and their fluctuations in the active site of enzymes affect efficient catalysis represents a critical objective of biochemical research. We have directly measured the dynamics of the electric field in the active site of a highly proficient enzyme, Δ(5)-3-ketosteroid isomerase (KSI), 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.1113874108
更新日期:2011-10-04 00:00:00
abstract::Chemical genomics is a powerful approach to dissect processes that may be intractable using conventional genetics because of gene lethality or redundancy. Recently, a link has been established between endomembrane trafficking and gravitropism. To understand this link, we screened a library of 10,000 diverse chemicals ...
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.0500222102
更新日期:2005-03-29 00:00:00
abstract::Single-stranded DNA oligonucleotides can achieve targeted base-pair substitution with modest efficiency but high precision. We show that "oligo targeting" can be used effectively to study missense mutations in DNA mismatch repair (MMR) genes. Inherited inactivating mutations in DNA MMR genes are causative for the canc...
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.1520813113
更新日期:2016-04-12 00:00:00
abstract::Thyrotropin-releasing hormone (TRH) binds to specific receptors on GH4C1 pituitary tumor cells. A fluorescently labeled analog of TRH was synthesized by coupling pGlu-His-ProNH(CH2)6NH2 to fluorescein isothiocyanate. The fluorescein-labeled peptide (FL-TRH) stimulated prolactin synthesis and release by GH4C1 cultures ...
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.78.1.587
更新日期:1981-01-01 00:00:00
abstract::After encoding, memory traces are initially fragile and have to be reinforced to become permanent. The initial steps of this process occur at a cellular level within minutes or hours. Besides this rapid synaptic consolidation, systems consolidation occurs within a time frame of days to years. For declarative memory, 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.0705454104
更新日期:2007-11-20 00:00:00
abstract::We compared private and social decision making to investigate the neural underpinnings of the effect of social comparison on risky choices. We measured brain activity using functional MRI while participants chose between two lotteries: in the private condition, they observed the outcome of the unchosen lottery, and in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.1100892108
更新日期:2011-09-20 00:00:00
abstract::IL-2-PE40 is a chimeric protein composed of human interleukin 2 (IL-2) genetically fused to the amino terminus of a modified form of Pseudomonas exotoxin lacking its cell recognition domain. IL-2-PE40, which is extremely cytotoxic to IL-2 receptor-positive cells, was examined for its ability to prevent graft rejection...
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.86.3.1008
更新日期:1989-02-01 00:00:00
abstract::Undesired side products of DNA transfections are usually discarded. However, here, we show that such products may provide insight into mutational events that are also a major driving force in protein evolution. While studying the small heat-shock protein alphaA-crystallin, we transfected the hamster alphaA-crystallin ...
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.96.14.8074
更新日期:1999-07-06 00:00:00
abstract::Taking advantage of a fluorescent Ca(2+) indicator selectively targeted to the trans-Golgi lumen, we here demonstrate that its Ca(2+) homeostatic mechanisms are distinct from those of the other Golgi subcompartments: (i) Ca(2+) uptake depends exclusively on the activity of the secretory pathway Ca(2+) ATPase1 (SPCA1),...
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.1004702107
更新日期:2010-05-18 00:00:00
abstract::The transcription factor caudal-type homeobox 1 (CDX1) is a key regulator of differentiation in the normal colon and in colorectal cancer (CRC). CDX1 activates the expression of enterocyte genes, but it is not clear how the concomitant silencing of stem cell genes is achieved. MicroRNAs (miRNAs) are important mediator...
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.1503370112
更新日期:2015-03-31 00:00:00
abstract::The clonal rat pituitary cell line GH4C1 expresses the genes for several voltage-dependent potassium channels including Kv1.5 and Kv1.4. Dexamethasone, a glucocorticoid agonist, induces a slowly inactivating potassium current in these cells but does not alter the amplitude of a rapidly inactivating component of potass...
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.92.13.5955
更新日期:1995-06-20 00:00:00
abstract::Most class I MHC ligands are generated from the vast majority of cellular proteins by proteolysis within the ubiquitin-proteasome pathway and are presented on the cell surface by MHC class I molecules. Here, we present the crystallographic analysis of yeast 20S proteasome in complex with the inhibitor homobelactosin 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.0600647103
更新日期:2006-03-21 00:00:00
abstract::As assessed by ultrastructure, histochemical staining, and T-cell dependency, in vitro-differentiated inter-leukin 3-dependent mouse mast cells are comparable to the mast cells that reside in the gastrointestinal mucosa but not in the skin or the serosal cavity of the mouse. We now demonstrate that when cloned interle...
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.85.2.569
更新日期:1988-01-01 00:00:00
abstract::Membrane-associated and periplasmic proteins of Agrobacterium tumefaciens C-58 were compared with those from avirulent (nontumrigenic) derivative strains by slab and two-dimensional gel electrophoresis. Two proteins (Per-I and Per-2), with a molecular weight of 37,500 and 37,300, respectively, were detected in the sup...
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.75.8.3796
更新日期:1978-08-01 00:00:00
abstract::The lectin chaperone calreticulin (CRT) assists the folding and quality control of newly synthesized glycoproteins in the endoplasmic reticulum (ER). It interacts with ERp57, a thiol-disulfide oxidoreductase that promotes the formation of disulfide bonds in glycoproteins bound by CRT. Here, we investigated the interac...
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.042699099
更新日期:2002-02-19 00:00:00
abstract::The androgen receptor (AR) binds to androgen response elements and regulates target genes via a mechanism involving coregulators. Here we demonstrate that the AR can interact with the testicular orphan receptor-4 (TR4) and function as a repressor to down-regulate the TR4 target genes by preventing the TR4 binding to 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.96.26.14724
更新日期:1999-12-21 00:00:00
abstract::The bactericidal effects of antibiotics are undoubtedly triggered by target-specific interactions, but there is growing evidence that an important aspect of cytotoxicity results from treatment-induced metabolic perturbations. In this study, we characterized molecular mechanisms whereby trimethoprim treatment results 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.1706236114
更新日期:2017-10-24 00:00:00
abstract::Real-time visualization of intracellular calcium concentration ([Ca2+]i) changes in mammalian Purkinje cells in vitro, utilizing the dye Fura-2, indicates that calcium action potentials are generated in the dendritic tree and follow a particular activation sequence. During spontaneous oscillations or after direct curr...
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.87.13.5084
更新日期:1990-07-01 00:00:00
abstract::Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system postulated to be a cell-mediated autoimmune disease in which interferon gamma (IFN-gamma) plays an important role. There is increased IFN-gamma secretion in MS, and IFN-gamma administration induces exacerbations of disease. We foun...
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.94.2.599
更新日期:1997-01-21 00:00:00
abstract::The last 2 decades have seen discoveries in highly excited states of atoms and molecules of phenomena that are qualitatively different from the "planetary" model of the atom, and the near-rigid model of molecules, characteristic of these systems in their low-energy states. A unified view is emerging in terms of approx...
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.93.25.14287
更新日期:1996-12-10 00:00:00
abstract::Proteins containing a caspase recruitment domain (CARD) play pivotal roles in signal transduction leading to apoptosis and NF-kappaB activation and inflammation. Here we identify and characterize human and mouse CARD protein 6 (CARD6), CARD-containing proteins of unique structure. CARD6 associates with microtubules 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.0510380103
更新日期:2006-01-24 00:00:00
abstract::The versatility of CRISPR-Cas endonucleases as a tool for biomedical research has led to diverse applications in gene editing, programmable transcriptional control, and nucleic acid detection. Most CRISPR-Cas systems, however, suffer from off-target effects and unpredictable nonspecific binding that negatively impact ...
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.1918685117
更新日期:2020-05-26 00:00:00
abstract::Metabolic imaging of the relative amounts of reduced NADH and FAD and the microenvironment of these metabolic electron carriers can be used to noninvasively monitor changes in metabolism, which is one of the hallmarks of carcinogenesis. This study combines cellular redox ratio, NADH and FAD lifetime, and subcellular 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.0708425104
更新日期:2007-12-04 00:00:00
abstract::Spontaneous cross-linking in vitro, during incubation of purified collagen in nonstriated and native type fibrils, was studied to elucidate the relationship between intra and intermolecular cross-links. In nonbanded fibrils, the aldol condensation products of two allysyl residues, previously shown to constitute the in...
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.67.3.1307
更新日期:1970-11-01 00:00:00
abstract::Low-dimensional objects such as molecular strands, ladders, and sheets have intrinsic features that affect their propensity to fold into 3D objects. Understanding this relationship remains a challenge for de novo design of functional structures. Using molecular dynamics simulations, we investigate the refolding of 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.1722681115
更新日期:2018-07-17 00:00:00
abstract::Electrogenic sodium- and chloride-dependent gamma-aminobutyric acid (GABA) transport in crude synaptosomal membrane vesicles is partly inhibited by saturating levels of either of the substrate analogues cis-3-aminocyclohexanecarboxylic acid (ACHC) or beta-alanine. However, both of them together potently and fully inhi...
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.87.7.2550
更新日期:1990-04-01 00:00:00
abstract::The folding energetics of the mono-N-glycosylated adhesion domain of the human immune cell receptor cluster of differentiation 2 (hCD2ad) were studied systematically to understand the influence of the N-glycan on the folding energy landscape. Fully elaborated N-glycan structures accelerate folding by 4-fold and stabil...
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.0810318105
更新日期:2009-03-03 00:00:00
abstract::In the absence of any overt task performance, it has been shown that spontaneous, intrinsic brain activity is expressed as systemwide, resting-state networks in the adult brain. However, the route to adult patterns of resting-state activity through neuronal development in the human brain is currently unknown. Therefor...
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.0704380104
更新日期:2007-09-25 00:00:00