Abstract：
:Improved techniques to noninvasively image protein-protein interactions (PPIs) are essential. We molecularly engineered a positron emission tomography (PET)-based split reporter (herpes simplex virus type 1 thymidine kinase), cleaved between Thr265 and Ala266, and used this in a protein-fragment complementation assay (PCA) to quantify PPIs in mammalian cells and to microPET image them in living mice. An introduced point mutation (V119C) markedly enhanced thymidine kinase complementation in PCAs, on the basis of rapamycin modulation of FKBP12-rapamycin-binding domain (FRB) and FKBP12 (FK506 binding protein), the interaction of hypoxia-inducible factor-1alpha with the von Hippel-Lindau tumor suppressor, and in an estrogen receptor intramolecular protein folding assay. Applications of this unique split thymidine kinase are potentially far reaching, including, for example, considerably more accurate monitoring of immune and stem cell therapies, allowing for fully quantitative and tomographic PET localization of PPIs in preclinical small- and large-animal models of disease.
journal_name
Nat Medjournal_title
Nature medicineauthors
Massoud TF,Paulmurugan R,Gambhir SSdoi
10.1038/nm.2185subject
Has Abstractpub_date
2010-08-01 00:00:00pages
921-6issue
8eissn
1078-8956issn
1546-170Xpii
nm.2185journal_volume
16pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract：:Beta-catenin is a central molecule in the Wnt pathway. Expression of a stable form of beta-catenin on CD4+CD25+ regulatory T (T(reg)) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable beta-catenin-expressing CD4+CD25+ T(reg) cells outcompeted control T(reg) cells in vivo, ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1707
更新日期：2008-02-01 00:00:00
abstract：:Hematopoietic stem and progenitor cells (HSPC) are endowed with the role of generating and maintaining lifelong the extremely diverse pool of blood cells1. Clinically, transplantation of human HSPC from an allogeneic healthy donor or infusion of autologous gene-corrected HSPC can effectively replenish defective blood ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-018-0195-3
更新日期：2018-11-01 00:00:00
abstract：:Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers gr...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.1891
更新日期：2008-12-01 00:00:00
abstract：:The rate of expansion of primary prostatic carcinoma is comparatively slow, with tumours frequently taking years or decades to reach clinically relevant size. We now report the presence of an endogenous inhibitor, derived from aqueous extracts of human prostate tissue, which blocks prostatic carcinoma cell proliferati...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1095-1040
更新日期：1995-10-01 00:00:00
abstract：:The mechanisms responsible for the persistence of HIV-1 after many years of suppressive antiretroviral therapy (ART) have been only partially elucidated. Most of the studies investigating HIV-1 persistence have been performed with blood, although it is well known that germinal centers (GCs) within lymph nodes (LNs) se...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.4113
更新日期：2016-07-01 00:00:00
abstract：:Synthetic vascular prostheses are foreign bodies, so that blood coagulation can occur on their luminal surfaces, causing graft occlusion very frequently in prostheses of small diameter. A vascular prosthesis needs angiogenesis for endothelialization of the luminal surface, as endothelial cells have natural and permane...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm0196-90
更新日期：1996-01-01 00:00:00
abstract：:The incidence of chronic pain is estimated to be 20-25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of th...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.2235
更新日期：2010-11-01 00:00:00
abstract：:Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a potentially fatal multiorgan inflammatory disease associated with herpesvirus reactivation and subsequent onset of autoimmune diseases1-4. Pathophysiology remains elusive and therapeutic options are limited. ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-019-0733-7
更新日期：2020-02-01 00:00:00
abstract：:The human CD4 molecule (hCD4) is expressed on T lymphocytes and macrophages and acts as a key component of the cellular receptor for HIV. At baseline, hCD4 transgenic mice expressed hCD4 on microglia, the resident mononuclear phagocytes of the brain, and showed no neuronal damage. Activation of brain microglia by peri...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm0498-441
更新日期：1998-04-01 00:00:00
abstract：:Although Nogo-A has been identified in the central nervous system as an inhibitor of axonal regeneration, the peripheral roles of Nogo isoforms remain virtually unknown. Here, using a proteomic analysis to identify proteins enriched in caveolae and/or lipid rafts (CEM/LR), we show that Nogo-B is highly expressed in cu...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1020
更新日期：2004-04-01 00:00:00
abstract：:Peripheral nerve injuries represent a significant problem in public health, constituting 2-5% of all trauma cases1. For severe nerve injuries, even advanced forms of clinical intervention often lead to incomplete and unsatisfactory motor and/or sensory function2. Numerous studies report the potential of pharmacologica...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-018-0196-2
更新日期：2018-12-01 00:00:00
abstract：:Systemic inflammation induces various adaptive responses including tachycardia. Although inflammation-associated tachycardia has been thought to result from increased sympathetic discharge caused by inflammatory signals of the immune system, definitive proof has been lacking. Prostanoids, including prostaglandin (PG) ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1231
更新日期：2005-05-01 00:00:00
abstract：:Atherosclerosis is an immunoinflammatory disease elicited by accumulation of lipids in the artery wall and leads to myocardial infarction and stroke. Here, we show that naturally arising CD4(+)CD25(+) regulatory T cells, which actively maintain immunological tolerance to self and nonself antigens, are powerful inhibit...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1343
更新日期：2006-02-01 00:00:00
abstract：:Cellular immunity has an inherent high level of functional heterogeneity. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. We report a microfluidic platform designed for highly multiplexed (more than ten proteins), reliable, sample-efficient (∼1...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.2375
更新日期：2011-06-01 00:00:00
abstract：:Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutrition...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.4280
更新日期：2017-03-01 00:00:00
abstract：:The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/9473
更新日期：1999-06-01 00:00:00
abstract：:We evaluated the ability of neonatal porcine islets to engraft and restore glucose control in pancreatectomized rhesus macaques. Although porcine islets transplanted into nonimmunosuppressed macaques were rapidly rejected by a process consistent with cellular rejection, recipients treated with a CD28-CD154 costimulati...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1375
更新日期：2006-03-01 00:00:00
abstract：:Matrix-producing osteoblasts and bone-resorbing osteoclasts maintain bone homeostasis. Osteoclasts are multinucleated, giant cells of hematopoietic origin formed by the fusion of mononuclear pre-osteoclasts derived from myeloid cells. Fusion-mediated giant cell formation is critical for osteoclast maturation; without ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1514
更新日期：2006-12-01 00:00:00
abstract：:The recent development of tissue microarrays-composed of hundreds of tissue sections from different tumors arrayed on a single glass slide-facilitates rapid evaluation of large-scale outcome studies. Realization of this potential depends on the ability to rapidly and precisely quantify the protein expression within ea...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm791
更新日期：2002-11-01 00:00:00
abstract：:Severe malaria is a major cause of childhood mortality in sub-Saharan Africa but the factors predisposing children to severe forms of malaria have not been fully elucidated. In a case-control study of over 1,200 Gambian children hepatitis B virus carriage was significantly increased amongst cases of severe malaria com...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm0495-374
更新日期：1995-04-01 00:00:00
abstract：:The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-020-1072-4
更新日期：2020-11-01 00:00:00
abstract：:We formulate a two-phase paradigm of autoimmunity associated with systemic lupus erythematosus, the archetypal autoimmune disease. The initial Toll-like receptor (TLR)-independent phase is mediated by dendritic cell uptake of apoptotic cell debris and associated nucleic acids, whereas the subsequent TLR-dependent phas...
journal_title：Nature medicine
pub_type： 杂志文章,评审
doi：10.1038/nm1590
更新日期：2007-05-01 00:00:00
abstract：:Evolutionary patterns of virus replication and distribution in lymphoid tissue during the early phases of HIV infection have not been delineated. Lymph node (LN) biopsies were excised from patients at different times after the estimated time of primary infection. Within 3 months of the acute viral syndrome, HIV was mo...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm0398-341
更新日期：1998-03-01 00:00:00
abstract：:Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest. Here we elucidate the structures of four new host-protective molecules produced in neutrophil-endothelial cocultures and present in human and mouse tissues after sterile inflammation or infecti...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.3911
更新日期：2015-09-01 00:00:00
abstract：: ...
journal_title：Nature medicine
pub_type： 评论,杂志文章
doi：10.1038/s41591-019-0397-3
更新日期：2019-03-01 00:00:00
abstract：:Overexpression of the normally imprinted fetal insulin-like growth factor II (IGF2) has been implicated in the pathogenesis of the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). We have detected constitutional relaxation of imprinting of IGF2 in four children with somatic overgrowth who do not show diagnostic ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm0396-311
更新日期：1996-03-01 00:00:00
abstract：:The ability of the human immune system to respond to vaccination declines with age. We identified an age-associated defect in T cell receptor (TCR)-induced extracellular signal-regulated kinase (ERK) phosphorylation in naive CD4(+) T cells, whereas other signals, such as ζ chain-associated protein kinase 70 (ZAP70) an...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.2963
更新日期：2012-10-01 00:00:00
abstract：:Recent studies of subjects infected with human immunodeficiency virus (HIV-1) have produced conflicting results about the extent of reconstitution possible in the CD4+ lymphocyte repertoire after highly active antiretroviral therapy (HAART). The effect of HAART on the incidence of opportunistic infections will probabl...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm0898-953
更新日期：1998-08-01 00:00:00
abstract：:Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interfere with PAF-induce...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm977
更新日期：2004-02-01 00:00:00
abstract：:Adequate lipid secretion by mammary glands during lactation is essential for the survival of mammalian offspring. However, the mechanism governing this process is poorly understood. Here we show that Cidea is expressed at high levels in lactating mammary glands and its deficiency leads to premature pup death as a resu...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.2614
更新日期：2012-01-15 00:00:00
