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Article ; Online: Letter to the Editor regarding to 'Activation of GLP-1 receptor signalling by sacubitril/valsartan: Implications for patients with poor glycaemic control'.

Wewer Albrechtsen, Nicolai J / Bojsen-Møller, Kirstine N

2022 Volume 368, Page(s) 55

MeSH term(s)	Aminobutyrates/pharmacology ; Aminobutyrates/therapeutic use ; Angiotensin Receptor Antagonists/pharmacology ; Angiotensin Receptor Antagonists/therapeutic use ; Biphenyl Compounds ; Drug Combinations ; Glucagon-Like Peptide-1 Receptor ; Glycemic Control ; Heart Failure/diagnosis ; Heart Failure/drug therapy ; Humans ; Stroke Volume ; Tetrazoles/pharmacology ; Tetrazoles/therapeutic use ; Treatment Outcome ; Valsartan
Chemical Substances	Aminobutyrates ; Angiotensin Receptor Antagonists ; Biphenyl Compounds ; Drug Combinations ; Glucagon-Like Peptide-1 Receptor ; Tetrazoles ; sacubitril (17ERJ0MKGI) ; Valsartan (80M03YXJ7I)
Language	English
Publishing date	2022-08-28
Publishing country	Netherlands
Document type	Letter ; Comment
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2022.08.048
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Article ; Online: Preanalytical impact on the accuracy of measurements of glucagon, GLP-1 and GIP in clinical trials.

Rasmussen, Christine / Richter, Michael M / Jensen, Nicole J / Heinz, Niklas / Hartmann, Bolette / Holst, Jens J / Kjeldsen, Sasha A S / Wewer Albrechtsen, Nicolai J

Scandinavian journal of clinical and laboratory investigation

2024 Volume 83, Issue 8, Page(s) 591–598

Abstract: Background: Plasma concentrations of glucagon, GLP-1 and GIP are reported in numerous clinical trials as outcome measures but preanalytical guidelines are lacking. We addressed the impact of commonly used blood containers in metabolic research on ... ...

Abstract	Background: Plasma concentrations of glucagon, GLP-1 and GIP are reported in numerous clinical trials as outcome measures but preanalytical guidelines are lacking. We addressed the impact of commonly used blood containers in metabolic research on measurements of glucagon, GLP-1 and GIP in humans. Methods: Seventeen overweight individuals were subjected to an overnight fast followed by an intravenous infusion of amino acids to stimulate hormonal secretion. Blood was sampled into five containers: EDTA-coated tubes supplemented with DMSO (control), a neprilysin inhibitor, aprotinin (a kallikrein inhibitor) or a DPP-4 inhibitor, and P800 tubes. Plasma was kept on ice before and after centrifugation and stored at -80 Celsius until batch analysis using validated sandwich ELISAs or radioimmunoassays (RIA). Results: Measures of fasting plasma glucagon did not depend on sampling containers, whether measured by ELISA or RIA. Amino acid-induced hyperglucagonemia was numerically higher when blood was collected into P800 tubes or tubes with aprotinin. The use of p800 tubes resulted in higher concentrations of GLP-1 by RIA compared to control tubes but not for measurements with sandwich ELISA. Plasma concentrations of GIP measured by ELISA were higher in control tubes and negatively affected by P800 and the addition of aprotinin. Conclusions: The choice of blood containers impacts on measurements of plasma concentrations of glucagon, GLP-1 and GIP, and based on this study, we recommend using EDTA-coated tubes without protease inhibitors or P800 tubes for measurements of glucagon, GLP-1 and GIP in clinical trials.
MeSH term(s)	Humans ; Glucagon/metabolism ; Glucagon-Like Peptide 1 ; Aprotinin ; Edetic Acid ; Gastric Inhibitory Polypeptide/metabolism ; Blood Glucose/analysis ; Insulin ; Peptide Fragments
Chemical Substances	Glucagon (9007-92-5) ; Glucagon-Like Peptide 1 (89750-14-1) ; Aprotinin (9087-70-1) ; Edetic Acid (9G34HU7RV0) ; Gastric Inhibitory Polypeptide (59392-49-3) ; Blood Glucose ; Insulin ; Peptide Fragments
Language	English
Publishing date	2024-01-24
Publishing country	England
Document type	Journal Article
ZDB-ID	3150-1
ISSN	1502-7686 ; 0036-5513
ISSN (online)	1502-7686
ISSN	0036-5513
DOI	10.1080/00365513.2023.2294470
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Article ; Online: Measurement of Gastrointestinal Hormones.

Albrechtsen, Nicolai J Wewer

Danish medical journal

2017 Volume 64, Issue 11

Abstract: ... as in subjects with diabetes or b) secretion of N-terminally elongated molecular forms (Study 4) in conditions ...

Abstract	Towards the end of the 20th century, the number of subjects with diabetes and obesity rose exponentially. The discoveries of insulin- and appetite-modulating chemical signals, including glucagon-like peptide-1 (GLP-1), secreted from the gastrointestinal system, led to development of a new group of drugs which now are being used for glucose-lowering therapy and weight loss. Understanding of the physiology of gut derived signals and their pathophysiologi-cal importance requires accurate measurements of their circulat-ing levels. However, the assessment of these gut-derived hor-mones has been hampered by numerous preanalytical and analyti-cal challenges. We focused on three members of the proglucagon family; glucagon, oxyntomodulin and GLP-1, aiming to meet both preanalytical and analytical challenges and to elucidate their implication in diseases including diabetes. First, we studied (Study 1) the preanalytical and storage conditions of GLP-1 and glucagon in humans, demonstrating that inappropriate sample handling may cause up to 50% variation in the RESULTS. Using robust meas-uring METHODS ensuring optimal conditions for preanalytical han-dling of these peptides, we then focused on plasma concentra-tions of glucagon and oxyntomodulin in different clinical condi-tions, including type 2 diabetes and bariatric surgery, because abnormal secretion of these hormones may represent early and specific signs of altered glucose metabolism. To that end, we developed an unbiased mass-spectrometry based platform for detection of low-abundant peptides, including the gut hormones (Study 2). Using the platform, we validated a new method for the measurement of oxyntomodulin, and in a series of in vitro, ex vivo, and clinical studies, we demonstrated that oxyntomodulin is co-distributed and co-secreted in response to glucose with GLP-1 and is degraded by dipeptidyl peptidase 4. Because oxyntomodulin has both GLP-1-like and glucagon-like bioactivity, the secretion of this hormone is of interest in both type 2 diabetes and bariatric sur-gery. Furthermore, using these newly developed METHODS, we subsequently were able to establish that elevated plasma concen-trations of glucagon (hyperglucagonemia) in diseases (Study 3) may be due to either a) increased secretion of fully processed glucagon, as in subjects with diabetes or b) secretion of N-terminally elongated molecular forms (Study 4) in conditions including bariatric surgery and in diseases affecting the kidneys. This glucagon variant may be of importance for glucose homeo-stasis, as we were able to show that it, unexpectedly, activates the glucagon receptor, leading to increased glycogenolysis in hepatocytes and insulin secretion from pancreatic beta-cells. In summary, accurate measurements of gut-derived hormones are indeed crucial for understanding their biology in health and as well in disease. Mass-spectrometry based plasma proteomics is a powerful tool for the validation of these METHODS.
MeSH term(s)	Bariatric Surgery ; Diabetes Mellitus, Type 2/blood ; Glucagon/blood ; Glucagon-Like Peptide 1/blood ; Humans ; Mass Spectrometry ; Neuropeptides/blood ; Obesity/blood ; Obesity/surgery ; Oxyntomodulin/blood ; Specimen Handling
Chemical Substances	Neuropeptides ; Oxyntomodulin ; Glucagon-Like Peptide 1 (89750-14-1) ; Glucagon (9007-92-5)
Language	English
Publishing date	2017-11
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	2648771-8
ISSN	2245-1919 ; 2245-1919
ISSN (online)	2245-1919
ISSN	2245-1919
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Article ; Online: Effect of a 6-Week Carbohydrate-Reduced High-Protein Diet on Levels of FGF21 and GDF15 in People With Type 2 Diabetes.

Richter, Michael M / Thomsen, Mads N / Skytte, Mads J / Kjeldsen, Sasha A S / Samkani, Amirsalar / Frystyk, Jan / Magkos, Faidon / Holst, Jens J / Madsbad, Sten / Krarup, Thure / Haugaard, Steen B / Wewer Albrechtsen, Nicolai J

Journal of the Endocrine Society

2024 Volume 8, Issue 4, Page(s) bvae008

Abstract: ... the interventions in a subset of samples (n = 24 in study 1, n = 66 in study 2).: Results: Plasma levels of FGF21 ...

Abstract	Context: Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are increased in type 2 diabetes and are potential regulators of metabolism. The effect of changes in caloric intake and macronutrient composition on their circulating levels in patients with type 2 diabetes are unknown. Objective: To explore the effects of a carbohydrate-reduced high-protein diet with and without a clinically significant weight loss on circulating levels of FGF21 and GDF15 in patients with type 2 diabetes. Methods: We measured circulating FGF21 and GDF15 in patients with type 2 diabetes who completed 2 previously published diet interventions. Study 1 randomized 28 subjects to an isocaloric diet in a 6 + 6-week crossover trial consisting of, in random order, a carbohydrate-reduced high-protein (CRHP) or a conventional diabetes (CD) diet. Study 2 randomized 72 subjects to a 6-week hypocaloric diet aiming at a ∼6% weight loss induced by either a CRHP or a CD diet. Fasting plasma FGF21 and GDF15 were measured before and after the interventions in a subset of samples (n = 24 in study 1, n = 66 in study 2). Results: Plasma levels of FGF21 were reduced by 54% in the isocaloric study ( Conclusion: The CRHP diet significantly reduced FGF21 in people with type 2 diabetes independent of weight loss, supporting the role of FGF21 as a "nutrient sensor." Combining metformin treatment with carbohydrate restriction and weight loss may provide additional metabolic improvements due to the rise in circulating GDF15.
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvae008
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Article: Detection of a 45 kD protein derived from the N terminus of the pea seedborne mosaic potyvirus polyprotein in vivo and in vitro.

Albrechtsen, M / Borkhardt, B

Virus genes

1994 Volume 8, Issue 1, Page(s) 7–13

Abstract: A 45 kD protein (Pro1) derived from the N terminus of the pea seedborne mosaic potyvirus (PSbMV ...

Abstract	A 45 kD protein (Pro1) derived from the N terminus of the pea seedborne mosaic potyvirus (PSbMV) polyprotein has been detected in extracts of infected pea plants and among in vitro translation products of PSbMV genomic RNA. The genomic region coding for the first 231 amino acids of the PSbMV polyprotein was cloned and expressed in Escherichia coli as a fusion protein with beta-galactosidase. A rabbit antiserum raised against the fusion protein recognized an approximately 45 kD protein in immunoblots of extracts of PSbMV-infected pea leaves that was not present in extracts of healthy leaves. The highest concentration of the 45 kD protein was found in extracts of young leaves, suggesting the protein may be rapidly degraded in vivo. After in vitro translation of PSbMV genomic RNA in a wheat germ extract, the antiserum immunoprecipitated a 45 kD polypeptide as well as some lower molecular weight translation products. On the other hand, an approximately 90 kD polypeptide was immunoprecipitated from in vitro translation products of genomic RNA in a rabbit reticulocyte lysate, corresponding to the combined molecular weights of Pro1 and the helper component predicted from genomic sequence data.
MeSH term(s)	Binding Sites ; Cloning, Molecular ; Escherichia coli/genetics ; Fabaceae/microbiology ; Molecular Weight ; Plants, Medicinal ; Potyvirus/genetics ; Potyvirus/metabolism ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/isolation & purification ; Viral Proteins/genetics ; Viral Proteins/isolation & purification ; Viral Proteins/metabolism
Chemical Substances	Recombinant Fusion Proteins ; Viral Proteins
Language	English
Publishing date	1994-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	639496-6
ISSN	1572-994X ; 0920-8569
ISSN (online)	1572-994X
ISSN	0920-8569
DOI	10.1007/bf01703597
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Zs.A 2397: Show issues

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Article: Observationally Weak TGFs in the RHESSI Data.

Albrechtsen, K H / Østgaard, N / Berge, N / Gjesteland, T

Journal of geophysical research. Atmospheres : JGR

2019 Volume 124, Issue 1, Page(s) 287–298

Abstract: Terrestrial gamma ray flashes (TGFs) are sub-millisecond bursts of high energetic gamma radiation associated with intracloud flashes in thunderstorms. In this paper we use the simultaneity of lightning detections by World Wide Lightning Location Network ... ...

Abstract	Terrestrial gamma ray flashes (TGFs) are sub-millisecond bursts of high energetic gamma radiation associated with intracloud flashes in thunderstorms. In this paper we use the simultaneity of lightning detections by World Wide Lightning Location Network to find TGFs in the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) data that are too faint to be identified by standard search algorithms. A similar approach has been used in an earlier paper, but here we expand the data set to include all years of RHESSI + World Wide Lightning Location Network data and show that there is a population of observationally weak TGFs all the way down to 0.22 of the RHESSI detection threshold (three counts in the detector). One should note that the majority of these are "normal" TGFs that are produced further away from the subsatellite point (and experience a 1/r
Language	English
Publishing date	2019-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	710256-2
ISSN	2169-8996 ; 2169-897X ; 0148-0227
ISSN (online)	2169-8996
ISSN	2169-897X ; 0148-0227
DOI	10.1029/2018JD029272
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Article ; Online: Individuals with type 2 diabetes have higher density of small intestinal neurotensin-expressing cells.

Ferreira, Filipa P / Pereira, Sofia S / Costa, Madalena M / Guimarães, Marta / Albrechtsen, Nicolai J Wewer / Holst, Jens J / Nora, Mário / Monteiro, Mariana P

Molecular and cellular biochemistry

2023 Volume 478, Issue 12, Page(s) 2779–2787

Abstract: ... small intestine fragments (n = 30) were obtained at every 20 cm along the entire intestinal length. Additionally ... jejunum biopsies (n = 29) were obtained during elective gastric bypass interventions from patients with (n ... 10) or without T2D (n = 18). NT-expressing cells were identified by immunohistochemistry and ...

Abstract	Neurotensin (NT) is a gastro-intestinal hormone involved in several pathways that regulate energy and glucose homeostasis. NT was hypothesized to act in synergy with incretin hormones to potentiate its anti-diabetic effects. Additionally, circulating NT levels were shown to rise after bariatric surgery-induced weight loss. Knowledge of NT-secreting cells distribution along the small intestine and its variation according to diabetes status could provide insights on NT role in mediating type 2 diabetes (T2D) improvement after bariatric surgery. So, our aims were to characterize NT-expressing cell distribution along the human small intestine and to compare the relative density of NT-expressing cells in the small intestine of individuals with and without T2D undergoing bariatric surgery for obesity treatment. Autopsy-derived small intestine fragments (n = 30) were obtained at every 20 cm along the entire intestinal length. Additionally, jejunum biopsies (n = 29) were obtained during elective gastric bypass interventions from patients with (n = 10) or without T2D (n = 18). NT-expressing cells were identified by immunohistochemistry and quantified via computerized morphometric analysis. NT-expressing cell density increased along the human small intestine. NT-expressing cell density was significantly higher from 200 cm distal to the duodenojejunal flexure onward, as well as in subjects with T2D when compared to those without T2D. NT-expressing cell density increases along the human small gut, and a higher density is found in individuals with T2D. This finding suggests a potential role for NT in the mechanisms of disease and T2D improvement observed after bariatric surgery.
MeSH term(s)	Humans ; Neurotensin/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Intestine, Small/metabolism ; Incretins/metabolism ; Gastric Bypass
Chemical Substances	Neurotensin (39379-15-2) ; Incretins
Language	English
Publishing date	2023-03-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-023-04698-z
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Zs.A 892: Show issues

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Article: The effect of exogenous glucagon on circulating amino acids in individuals with and without type 2 diabetes and obesity.

Grøndahl, Magnus F G / Bagger, Jonatan I / Suppli, Malte P / Van Hall, Gerrit / Albrechtsen, Nicolai J W / Holst, Jens J / Vilsbøll, Tina / Christensen, Mikkel B / Lund, Asger B / Knop, Filip K

Endocrine connections

2024 Volume 13, Issue 3

Abstract: ... performed in individuals with type 2 diabetes (n = 16) and in age, sex, and body mass index-matched control ... individuals without diabetes (n = 16). Each group comprised two subgroups of eight individuals with and ...

Abstract	Objective: In obesity and type 2 diabetes, hyperglucagonaemia may be caused by elevated levels of glucagonotropic amino acids due to hepatic glucagon resistance at the level of amino acid turnover. Here, we investigated the effect of exogenous glucagon on circulating amino acids in obese and non-obese individuals with and without type 2 diabetes. Design: This was a post hoc analysis in a glucagon infusion study performed in individuals with type 2 diabetes (n = 16) and in age, sex, and body mass index-matched control individuals without diabetes (n = 16). Each group comprised two subgroups of eight individuals with and without obesity, respectively. Methods: All participants received a 1-h glucagon infusion (4 ng/kg/min) in the overnight fasted state. Plasma amino acid concentrations were measured with frequent intervals. Results: Compared to the control subgroup without obesity, baseline total amino acid levels were elevated in the control subgroup with obesity and in the type 2 diabetes subgroup without obesity. In all subgroups, amino acid levels decreased by up to 20% in response to glucagon infusion, which resulted in high physiological steady-state glucagon levels (mean concentration: 74 pmol/L, 95% CI [68;79] pmol/L). Following correction for multiple testing, no intergroup differences in changes in amino acid levels reached significance. Conclusion: Obesity and type 2 diabetes status was associated with elevated fasting levels of total amino acids. The glucagon infusion decreased circulating amino acid levels similarly in all subgroups, without significant differences in the response to exogenous glucagon between individuals with and without obesity and type 2 diabetes. Significance statement: The hormone glucagon stimulates glucose production from the liver, which may promote hyperglycaemia if glucagon levels are abnormally elevated, as is often seen in type 2 diabetes and obesity. Glucagon levels are closely linked to, and influenced by, the levels of circulating amino acids. To further investigate this link, we measured amino acid levels in individuals with and without obesity and type 2 diabetes before and during an infusion of glucagon. We found that circulating amino acid levels were higher in type 2 diabetes and obesity, and that glucagon infusion decreased amino acid levels in both individuals with and without type 2 diabetes and obesity. The study adds novel information to the link between circulating levels of glucagon and amino acids.
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2668428-7
ISSN	2049-3614
ISSN	2049-3614
DOI	10.1530/EC-23-0516
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Article: Characterization of human neutrophil glycoproteins expressing the CD15 differentiation antigen (3-fucosyl-N-acetyllactosamine).

Albrechtsen, M / Kerr, M A

British journal of haematology

1989 Volume 72, Issue 3, Page(s) 312–320

Abstract: The expression of the CD15 antigen, 3-fucosyl N-acetyllactosamine, on neutrophil glycoproteins has ...

Abstract	The expression of the CD15 antigen, 3-fucosyl N-acetyllactosamine, on neutrophil glycoproteins has been studied by SDS gel electrophoresis and immunoblotting. The antigen is expressed on several glycoproteins, both intracellularly and on the cell surface. Each subcellular compartment appears to contain a specific antigen. A soluble, granule glycoprotein (Mr 80-90K) probably accounts for most of the intracellular staining detected immunohistochemically. Membrane glycoproteins of Mr, 85-90K and 25K are associated with granule membranes, the latter being an integral membrane protein. The CD15 antigen is expressed on several cell surface glycoproteins with Mr in the range of 165K and 105K. These antigens are also contained in an intracellular pool which is brought to the surface on activation of the cells with chemotactic peptides. The 165K and 105K antigens show identical electrophoretic mobility to two of the major glycoproteins detectable by PAS or protein staining of gels of detergent extracts of cell membranes. These glycoproteins include the complement receptor, CR3. The beta chain of CR3 (105K) and to a lesser extent the alpha chain (165K) express CD15; however, most of the CD15 antigen is associated with other glycoproteins of these molecular masses.
MeSH term(s)	Antibodies, Monoclonal ; Antigens, Differentiation ; Electrophoresis, Polyacrylamide Gel ; Glycoproteins/analysis ; Glycoproteins/immunology ; Humans ; Immunoblotting ; Lewis X Antigen/analysis ; Membrane Glycoproteins/immunology ; Neutrophils/immunology
Chemical Substances	Antibodies, Monoclonal ; Antigens, Differentiation ; Glycoproteins ; Lewis X Antigen ; Membrane Glycoproteins
Language	English
Publishing date	1989-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/j.1365-2141.1989.tb07710.x
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Article: Glial cells express N-CAM/D2-CAM-like polypeptides in vitro.

Noble, M / Albrechtsen, M / Møller, C / Lyles, J / Bock, E / Goridis, C / Watanabe, M / Rutishauser, U

Nature

1985 Volume 316, Issue 6030, Page(s) 725–728

Abstract: ... neurones involves a glycoprotein that has been independently studied under the names of N-CAM ... for neural cell adhesion molecule), D2-CAM and BSP-2 (refs 10, 11). As N-CAM/D2-CAM appears to be a homophilic ligand that binds ... to N-CAM/D2-CAM polypeptide on adjacent cells, this glycoprotein is potentially important in adhesion ...

Abstract	The joining together of neurites to form fascicles and the growth of axons along glial surfaces during early development suggest that neurone-neurone and neurone-glial adhesion interactions are of considerable importance for defining nerve tracts. In vitro studies have indicated that adhesion between neurones involves a glycoprotein that has been independently studied under the names of N-CAM (for neural cell adhesion molecule), D2-CAM and BSP-2 (refs 10, 11). As N-CAM/D2-CAM appears to be a homophilic ligand that binds to N-CAM/D2-CAM polypeptide on adjacent cells, this glycoprotein is potentially important in adhesion interactions between any two N-CAM/D2-CAM-expressing cells. While it has been suggested that neurone-glial adhesion involves molecules other than N-CAM/D2-CAM, it is known that N-CAM/D2-CAM antigenic determinants are expressed by glial cells in vivo and that injection of anti-N-CAM antibodies into the eye-cup of chick embryos disrupts normal patterns of neuritic apposition to glial endfeet in the developing optic stalk. Do the molecules expressed by glia share restricted antigenic determinants, or binding domains, with N-CAM/D2-CAM, or are N-CAM/D2-CAM polypeptides expressed by glia? Here we present immunocytochemical evidence which suggests that all classes of macroglia express N-CAM/D2-CAM antigenic determinants on their surfaces and immunochemical analyses which indicate that the molecules expressed by purified astrocytes are closely similar, or identical, to at least some forms of N-CAM/D2-CAM obtained from whole brain or purified neurones. However, our results also suggest that different N-CAM/D2-CAM polypeptides may be separately expressed by neurones and astrocytes.
MeSH term(s)	Animals ; Antigens, Surface/analysis ; Antigens, Surface/immunology ; Astrocytes/analysis ; Cell Adhesion Molecules ; Epitopes/analysis ; In Vitro Techniques ; Mice ; Molecular Weight ; Neuroglia/analysis ; Rabbits ; Rats ; Schwann Cells/analysis
Chemical Substances	Antigens, Surface ; Cell Adhesion Molecules ; Epitopes
Language	English
Publishing date	1985-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/316725a0
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