684 research outputs found
Strategy Choices of Foreign Policy Decision Makers THE NETHERLANDS, 1914
The assessment of the selection of strategy is studied using documents of a specific case of Dutch foreign policy from the beginning of World War I. First, a content analysis procedure was developed in order to search for the relevant concepts in the documents and to represent the argumentations in decision trees. Thereafter, the applicability of several decision critena to the data is discussed. In order to describe the data, an alternative decision rule had to be developed, one which can be considered an adaptation of Simon's satisficing principle
Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men
AIMS/HYPOTHESIS: Obesity is characterised by increased triacylglycerol storage in adipose tissue. There is in vitro evidence for a blunted beta-adrenergically mediated lipolytic response in abdominal subcutaneous adipose tissue (SAT) of obese individuals and evidence for this at the whole-body level in vivo. We hypothesised that the beta-adrenergically mediated effect on lipolysis in abdominal SAT is also impaired in vivo in obese humans. METHODS: We investigated whole-body and abdominal SAT glycerol metabolism in vivo during 3 h and 6 h [2H5]glycerol infusions. Arterio-venous concentration differences were measured in 13 lean and ten obese men after an overnight fast and during intravenous infusion of the non-selective beta-adrenergic agonist isoprenaline [20 ng (kg fat free mass)(-1) min(-1)]. RESULTS: Lean and obese participants showed comparable fasting glycerol uptake by SAT (9.7+/-3.4 vs 9.3+/-2.5% of total release, p=0.92). Furthermore, obese participants showed an increased whole-body beta-adrenergically mediated lipolytic response versus lean participants. However, their fasting lipolysis was blunted [glycerol rate of appearance: 7.3+/-0.6 vs 13.1+/-0.9 micromol (kg fat mass)(-1) min(-1), p<0.01], as was the beta-adrenergically mediated lipolytic response per unit SAT [Delta total glycerol release: 140+/-71 vs 394+/-112 nmol (100 g tissue)(-1) min(-1), p<0.05] compared with lean participants. Net triacylglycerol flux tended to increase in obese compared with lean participants during beta-adrenergic stimulation [Delta net triacylglycerol flux: 75+/-32 vs 16+/-11 nmol (100 g tissue)(-1) min(-1), p=0.06]. CONCLUSIONS/INTERPRETATION: We demonstrated in vivo that beta-adrenergically mediated lipolytic response is impaired systematically and in abdominal SAT of obese versus lean men. This may be important in the development or maintenance of increased triacylglycerol stores and obesity
AntiâcNâ1A autoantibodies are absent in juvenile dermatomyositis
Objectives:
To assess antiâcytosolic 5âČânucleotidase 1A (cNâ1A/NTC51A) autoantibodies in children with juvenile dermatomyositis (JDM) and healthy controls, using three different methods of antibody detection, as well as verification of the results in an independent cohort.
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Methods:
AntiâcNâ1A reactivity was assessed in 34 Dutch JDM patients and 20 healthy juvenile controls by a commercially available fullâlength cNâ1A ELISA, a synthetic peptide ELISA and by immunoblotting using a lysate from cNâ1A expressing HEKâ293 cells. Sera from JDM patients with active disease and in remission were analysed. An independent British cohort of 110 JDM patients and 43 healthy juvenile controls was assessed by an inâhouse fullâlength cNâ1A ELISA.
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Results:
AntiâcNâ1A reactivity was not present in JDM patientsâ sera or in healthy controls when tested with the commercially available fullâlength cNâ1A ELISA or by immunoblotting, both in active disease and in remission. Also, in the British JDM cohort antiâcNâ1A reactivity was not detected. Three Dutch JDM patients tested weakly positive for one of the three synthetic cNâ1A peptides measured by ELISA.
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Conclusion:
JDM patients and young healthy individuals do not show antiâcNâ1A reactivity as assessed by different antibody detection techniques
Prorenin accumulation and activation in human endothelial cells: importance of mannose 6-phosphate receptors
ACE inhibitors improve endothelial dysfunction, possibly by blocking
endothelial angiotensin production. Prorenin, through its binding and
activation by endothelial mannose 6-phosphate (M6P) receptors, may
contribute to this production. Here, we investigated this possibility as
well as prorenin activation kinetics, the nature of the
prorenin-activating enzyme, and M6P receptor-independent prorenin binding.
Human umbilical vein endothelial cells (HUVECs) were incubated with
wild-type prorenin, K/A-2 prorenin (in which Lys42 is mutated to Ala,
thereby preventing cleavage by known proteases), M6P-free prorenin, and
nonglycosylated prorenin, with or without M6P, protease inhibitors, or
angiotensinogen. HUVECs bound only M6P-containing prorenin (K(d) 0.9+/-0.1
nmol/L, maximum number of binding sites [B(max)] 1010+/-50
receptors/cell). At 37 degrees C, because of M6P receptor recycling, the
amount of prorenin internalized via M6P receptors was >25 times B(max).
Inside the cells, wild-type and K/A-2 prorenin were proteolytically
activated to renin. Renin was subsequently degraded. Protease inhibitors
interfered with the latter but not with prorenin activation, thereby
indicating that the activating enzyme is different from any of the known
prorenin-activating enzymes. Incubation with angiotensinogen did not lead
to endothelial angiotensin generation, inasmuch as HUVECs were unable to
internalize angiotensinogen. Most likely, therefore, in the absence of
angiotensinogen synthesis or endocytosis, M6P receptor-mediated prorenin
internalization by endothelial cells represents prorenin clearance
Systematic Control of the Orientation of Organic Phosphorescent Pt Complexes in Thin Films for Increased Optical Outcoupling
Orienting lightâemitting molecules relative to the substrate is an effective method to enhance the optical outcoupling of organic lightâemitting devices. Platinum(II) phosphorescent complexes enable facile control of the molecular alignment due to their planar structures. Here, the orientation of Pt(II) complexes during the growth of emissive layers is controlled by two different methods: modifying the molecular structure and using structural templating. Molecules whose structures are modified by adjusting the diketonate ligand of the Pt complex, dibenzoâ(f,h)quinoxaline Pt dipivaloylmethane, (dbx)Pt(dpm), show an â20% increased fraction of horizontally aligned transition dipole moments compared to (dbx)Pt(dpm) doped into a 4,4âČâbis(Nâcarbazolyl)â1,1âČâbiphenyl, CBP, host. Alternatively, a template composed of highly ordered 3,4,9,10âperylenetetracarboxylic dianhydride monolayers is predeposited to drive the alignment of a subsequently deposited emissive layer comprising (2,3,7,8,12,13,17,18âoctaethyl)â21H,23Hâporphyrinplatinum(II) doped into triindolotriazine. This results in a 60% increase in horizontally aligned transition dipole moments compared to the film deposited in the absence of the template. The findings provide a systematic route for controlling molecular alignment during layer growth, and ultimately to increase the optical outcoupling in organic lightâemitting diodes.Pt(II) complex orientation is controlled by modifying the molecular structure and structural templating. Molecules with modified structures show â20% increased fraction of horizontally aligned transition dipole moments (TDMs) when doped into a host. Alternatively, a highly ordered molecular template drives the alignment of a subsequently deposited polycrystalline emissive layer, showing a 60% increase in horizontally aligned TDMs versus without template.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151333/1/adma201900921.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151333/2/adma201900921_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151333/3/adma201900921-sup-0001-S1.pd
Prorenin anno 2008
For many years, prorenin has been considered to be nothing more than the inactive precursor of renin. Yet, its elevated levels in diabetic subjects with microvascular complications and its extrarenal production at various sites in the body suggest otherwise. This review discusses the origin, regulation, and enzymatic activity of prorenin, its role during renin inhibition, and the angiotensin-dependent and angiotensin-independent consequences of its binding to the recently discovered (pro)renin receptor. The review ends with the concept that prorenin rather than renin determines tissue angiotensin generation
Subcutaneous Adipose Tissue and Systemic Inflammation Are Associated With Peripheral but Not Hepatic Insulin Resistance in Humans
Obesity-related insulin resistance (IR) may develop in multiple organs, representing different etiologies towards cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in relation to liver or muscle IR by means of RNA sequencing in overweight/obese participants of the DiOGenes cohort (n=368). Tissue-specific IR phenotypes were derived from a 5-point oral glucose tolerance test. Hepatic and muscle IR were characterized by distinct abdominal ScAT transcriptome profiles. Genes related to extracellular remodeling were upregulated in individuals with primarily hepatic IR, whilst genes related to inflammation were upregulated in individuals with primarily muscle IR. In line with this, in two independent cohorts, CODAM (n=325) and the Maastricht Study (n=685), an increased systemic low-grade inflammation profile was specifically related to muscle IR, but not to liver IR. We propose that increased ScAT inflammatory gene expression may translate into an increased systemic inflammatory profile, linking ScAT inflammation to the muscle IR phenotype. These distinct IR phenotypes may provide leads for more personalized prevention of cardiometabolic diseases. DiOGenes was registered at clinicaltrials.gov as NCT00390637
Adipose triglyceride lipase (ATGL) expression in human skeletal muscle is type I (oxidative) fiber specific
Accumulation of triacylglycerol (TAG) and lipid intermediates in skeletal muscle plays an important role in the etiology of insulin resistance and type 2 diabetes mellitus. Disturbances in skeletal muscle lipid turnover and lipolysis may contribute significantly to this. So far, knowledge on the regulation of muscle lipolysis is limited. Recently the identification of a new lipase was reported: adipose triglyceride lipase (ATGL). ATGL deficient animals show significant lipid accumulation in skeletal muscle, which may indicate that ATGL plays a pivotal role in skeletal muscle lipolysis. However, until now, it is still unknown whether ATGL protein is expressed in human skeletal muscle. Therefore, the aim of the present study was to investigate whether ATGL is expressed at the protein level in human skeletal muscle, and to examine whether its expression is fiber-type specific. To accomplish this, we established an imunohistochemical and immunofluorescent staining procedure to study ATGL protein expression in relation to fiber type in human vastus lateralis muscle of eight male subjects (BMI range: 21.0â34.5Â kg/m2 and age: 38â59Â years). In the present paper we report for the first time that ATGL protein is indeed expressed in human skeletal muscle. Moreover, ATGL is exclusively expressed in type I (oxidative) muscle fibers, suggesting a pivotal role for ATGL in intramuscular fatty acid handling, lipid storage and breakdown
Hormone-Sensitive Lipase Serine Phosphorylation and Glycerol Exchange Across Skeletal Muscle in Lean and Obese Subjects : Effect of ÎČ-Adrenergic Stimulation
OBJECTIVEâIncreased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin-resistant state. We aimed to investigate whether a blunted fasting or ÎČ-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity
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