Abstract:
:Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparum can adhere to specific receptors on host cells, an important virulence factor enabling parasites to accumulate in various organs. We report here that most P. falciparum isolates from infected placentae can bind to hyaluronic acid, a newly discovered receptor for parasite adhesion that is present on the placental lining. In laboratory isolates selected for specific high-level adhesion, binding to hyaluronic acid could be inhibited by dodecamer or larger oligosaccharide fragments or polysaccharides, treatment of immobilized receptor with hyaluronidase, or treatment of infected erythrocytes with trypsin. In vitro flow-based assays demonstrated that high levels of adhesion occurred at low wall shear stress, conditions thought to prevail in the placenta. Our findings indicate that adhesion to hyaluronic acid is involved in mediating placental parasite accumulation, thus changing the present understanding of the mechanisms of placental infection, with implications for the development of therapeutic and preventative interventions.
journal_name
Nat Medjournal_title
Nature medicineauthors
Beeson JG,Rogerson SJ,Cooke BM,Reeder JC,Chai W,Lawson AM,Molyneux ME,Brown GVdoi
10.1038/71582keywords:
subject
Has Abstractpub_date
2000-01-01 00:00:00pages
86-90issue
1eissn
1078-8956issn
1546-170Xjournal_volume
6pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/78682
更新日期:2000-08-01 00:00:00
abstract::Increased production of very low-density lipoprotein (VLDL) is a critical feature of the metabolic syndrome. Here we report that a selective increase in brain glucose lowered circulating triglycerides (TG) through the inhibition of TG-VLDL secretion by the liver. We found that the effect of glucose required its conver...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1540
更新日期:2007-02-01 00:00:00
abstract::During fasting, induction of hepatic gluconeogenesis is crucial to ensure proper energy homeostasis. Such induction is dysregulated in type 2 diabetes, resulting in the development of fasting hyperglycemia. Hormonal and nutrient regulation of metabolic adaptation during fasting is mediated predominantly by the transcr...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2691
更新日期:2012-03-18 00:00:00
abstract::The mechanism underlying the autoimmune polyglandular syndrome type-1 (APS1) has been attributed to defective T-cell negative selection resulting from reduced expression and presentation of autoantigens in thymic medullary epithelial cells (MECs). It has also been postulated that Aire is involved in development of reg...
journal_title:Nature medicine
pub_type: 杂志文章,收录出版
doi:10.1038/nm1424
更新日期:2006-06-01 00:00:00
abstract::A chimeric RNA/DNA oligonucleotide was constructed to induce a sequence mutation in the rat factor IX gene, resulting in prolonged coagulation. Oligonucleotides were targeted to hepatocytes in cell culture or in vivo by intravenous injection. Nucleotide conversion was both site-specific and dose-dependent. The mutated...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0398-285
更新日期:1998-03-01 00:00:00
abstract::HIV infection can cause extensive neuronal loss and clinically a severe dementia. The cause of the neurotoxicity remains unclear as neurons are not infected, but disturbance of glutamate-linked calcium entry has been implicated. In this study, we have shown a decrease in HIV-infected brain of the expression of mRNA an...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1195-1174
更新日期:1995-11-01 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 bromodomain and extraterminal (BET) family of proteins comprises four members-BRD2, BRD3, BRD4 and the testis-specific isoform BRDT-that largely function as transcriptional coactivators and play critical roles in various cellular processes, including the cell cycle, apoptosis, migration and invasion. BET proteins ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4378
更新日期:2017-09-01 00:00:00
abstract::Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodeficiency virus of macaques (SIVmac). In contrast, during nonpathoge...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4421
更新日期:2017-11-01 00:00:00
abstract::Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signature...
journal_title:Nature medicine
pub_type: 杂志文章,收录出版
doi:10.1038/nm1491
更新日期:2006-11-01 00:00:00
abstract::Advances in imaging are transforming our understanding of angiogenesis and the evaluation of drugs that stimulate or inhibit angiogenesis in preclinical models and human disease. Vascular imaging makes it possible to quantify the number and spacing of blood vessels, measure blood flow and vascular permeability, and an...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm0603-713
更新日期:2003-06-01 00:00:00
abstract::In the version of this article originally published, a grant was omitted from the Acknowledgements section. The following sentence should have been included: "R.B.M. was supported by a Department of Veterans Affairs Merit Award (5I01BX003272)." The error has been corrected in the HTML and PDF versions of this article....
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-018-0170-z
更新日期:2018-10-01 00:00:00
abstract::Technologies are needed to map and image biological barriers in vivo that limit solid tumor delivery and, ultimately, the effectiveness of imaging and therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae at the blood-tumor interface to discover an active transendothelial portal to infiltrat...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3623
更新日期:2014-09-01 00:00:00
abstract::Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and surviva...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2819
更新日期:2012-07-01 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::Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14-15 °C) increased peripheral insulin sensitivity by ∼43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, wit...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3891
更新日期:2015-08-01 00:00:00
abstract::Atherosclerosis is a systemic disease of the large arteries, and activation of inflammatory pathways is important in its pathogenesis. Increasing evidence supports the importance of CD40-CD154 interactions in atherosclerosis, interactions originally known to be essential in major immune reactions and autoimmune diseas...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/15271
更新日期:1999-11-01 00:00:00
abstract::Genetic alterations in malignant tissues are potential targets for gene-based cancer therapies. Alternatively, aberrant expression of certain specific genes associated with malignant transformation may be envisioned to enhance the expression of chemosensitizing drugs. Epstein-Barr virus (EBV)-related B-cell lymphomas ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1296-1379
更新日期:1996-12-01 00:00:00
abstract::Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcripto...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0654-5
更新日期:2019-12-01 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::A high-fat diet increases the risk of colon, breast and prostate cancer. The molecular mechanism by which dietary lipids promote tumorigenesis is unknown. Their effects may be mediated at least in part by the peroxisome proliferator-activated receptors (PPARs). These ligand-activated nuclear receptors modulate gene ex...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/2042
更新日期:1998-09-01 00:00:00
abstract::Accumulation of fibrils composed of amyloid A in tissues resulting in displacement of normal structures and cellular dysfunction is the characteristic feature of systemic amyloidoses. Here we show that RAGE, a multiligand immunoglobulin superfamily cell surface molecule, is a receptor for the amyloidogenic form of ser...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/76216
更新日期:2000-06-01 00:00:00
abstract::Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism in starving cells. Although altered autophagy has been observed in various heart diseases, including cardiac hypertrophy and heart failure, it remains unclear whether autophagy plays a...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1574
更新日期:2007-05-01 00:00:00
abstract::The inwardly rectifying K(+) channel Kir6.1 forms K(+) channels by coupling with a sulfonylurea receptor in reconstituted systems, but the physiological roles of Kir6.1-containing K(+) channels have not been determined. We report here that mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudd...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0502-466
更新日期:2002-05-01 00:00:00
abstract::How high salt intake increases blood pressure is a key question in the study of hypertension. Salt intake induces increased renal sympathetic activity resulting in sodium retention. However, the mechanisms underlying the sympathetic control of renal sodium excretion remain unclear. In this study, we found that β(2)-ad...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2337
更新日期:2011-05-01 00:00:00
abstract::The androgen receptor (AR) is involved in the development, growth and progression of prostate cancer (CaP). CaP often progresses from an androgen-dependent to an androgen-independent tumor, making androgen ablation therapy ineffective. However, the mechanisms for the development of androgen-independent CaP are unclear...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/76287
更新日期:2000-06-01 00:00:00
abstract::Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and id...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4038
更新日期:2016-03-01 00:00:00
abstract::Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G>A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responde...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4401
更新日期:2017-10-01 00:00:00
abstract::The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but understanding of host-commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3929
更新日期:2015-09-01 00:00:00
abstract::Both the risk and the rate of development of atherosclerosis are increased in diabetics, but the mechanisms involved are unknown. Here we report a glucose-mediated increase in CD36 mRNA translation efficiency that results in increased expression of the macrophage scavenger receptor CD36. Expression of CD36 was increas...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/89969
更新日期:2001-07-01 00:00:00