Integrative Proteomic Profiling Reveals PRC2-Dependent Epigenetic Crosstalk Maintains Ground-State Pluripotency

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The role of thrombin in the regulation of the endothelial prostaglandin production

Prostaglandin synthesis in endothelial cells may be initiated by the addition of exogenous substrate (arachidonic acid) or by addition of thrombin or the CA2+-ionophore A23187, which leads to prostacyclin formation from endogenous substrates. We noticed that endothelial cells produce more than twice the amount of prostacyclin when incubated with thrombin and arachidonic acid together than with arachidonic acid alone. In addition, it was found that the thrombin-induced conversion of endogenous substrates was inhibited by exogenous arachidonic acid. This means that the conversion of exogenous added arachidonic acid to prostacyclin was stimulated by thrombin. This activation of the enzymes involved in prostacyclin synthesis lasted about 5 min and could be inhibited by phospholipase inhibitors such as mepacrine and p-bromophenyl-acylbromide but not by the cAMP analogue dibutyryl cAMP, an inhibitor of arachidonic acid release from cellular phospholipids. These data demonstrate that, in addition to causing release of endogenous substrate, thrombin and the Ca2+-ionophore also activate the enzyme system involved in the further transformation of arachidonic acid.     

Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1).

IGF-I and IGF-II are growth-stimulating peptides with strong mitogenic properties. These polypeptide growth factors circulate in serum bound to specific binding proteins. We report the cloning and complete sequence of a cDNA encoding a low mol. wt IGF-binding protein from a human placenta cDNA library. We propose the designation IGF-binding protein 1 (IBP-1) for the gene and corresponding protein. Expression of the cDNA encoding IBP-1 in COS cells resulted in the synthesis of a 30-kd protein which binds IGF-I and is immunologically indistinguishable from the IGF-binding protein isolated from amniotic fluid or human serum. Northern blotting analysis demonstrated that expression of the IBP-1 gene is highly tissue specific and limited to placental membranes and fetal liver suggesting a rigid control. The IBP-1 gene is a single copy gene, located on chromosome 7. The results obtained suggest that most, if not all, lower mol. wt IGF-binding proteins originate from this gene.     

Action of histamine and its receptor blockers on uterine circulation in sheep.

Effects of iv and ia administration of histamine and its H1 and H2 blockers (diphenhydramine and metiamide) on systemic arterial pressure, heart rate, and uterine and iliac blood flows were investigated in unanesthetized, chronically instrumented nonpregnant ewes. Intravenous histamine produced tachycardia, hypotension, and decreased iliac and uterine blood flows. In contrast, ia injections produced a significant increase in blood flows in these vascular beds which was dose-dependent. Evidence is presented to show that some of the circulatory actions of histamine may be related to stimulation of H1 while others may be related to H2 receptors. The peripheral circulatory action produced by iv histamine is probably secondary to its effects on reducing cardiac output. The uterine and iliac vascular beds contain mostly H1 receptors since their response to histamine can be blocked almost totally by Benadryl and not by H2 antagonist metiamide.     

Molecular characterization of enterobacterial pldA genes encoding outer membrane phospholipase A.

The pldA gene of Escherichia coli encodes an outer membrane phospholipase A. A strain carrying the most commonly used mutant pldA allele appeared to express a correctly assembled PldA protein in the outer membrane. Nucleotide sequence analysis revealed that the only difference between the wild type and the mutant is the replacement of the serine residue in position 152 by phenylalanine. Since mutants that lack the pldA gene were normally viable under laboratory conditions and had no apparent phenotype except for the lack of outer membrane phospholipase activity, the exact role of the enzyme remains unknown. Nevertheless, the enzyme seems to be important for the bacteria, since Western blotting (immunoblotting) and enzyme assays showed that it is widely spread among species of the family Enterobacteriaceae. To characterize the PldA protein further, the pldA genes of Salmonella typhimurium, Klebsiella pneumoniae, and Proteus vulgaris were cloned and sequenced. The cloned genes were expressed in E. coli, and their gene products were enzymatically active. Comparison of the predicted PldA primary structures with that of E. coli PldA revealed a high degree of homology, with 79% of the amino acid residues being identical in all four proteins. Implications of the sequence comparison for the structure and the structure-function relationship of PldA protein are discussed.     

A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease

Prior to the implementation of predictive-testing programs for Huntington disease (HD), significant concern was raised concerning the likelihood of catastrophic events (CEs), particularly in those persons receiving an increased-risk result. We have investigated the frequency of CEs-that is, suicide, suicide attempt, and psychiatric hospitalization-after an HD predictive-testing result, through questionnaires sent to predictive-testing centers worldwide. A total of 44 persons (0.97%) in a cohort of 4,527 test participants had a CE: 5 successful suicides, 21 suicide attempts, and 18 hospitalizations for psychiatric reasons. All persons committing suicide had signs of HD, whereas 11 (52.4%) of 21 persons attempting suicide and 8 (44.4%) of 18 who had a psychiatric hospitalization were symptomatic. A total of 11 (84.6%) of 13 asymptomatic persons who experienced a CE during the first year after HD predictive testing received an increased-risk result. Factors associated with an increased risk of a CE included (a) a psychiatric history 相似文献   

Prophylaxis and follow-up after possible exposure to HIV,hepatitis B virus,and hepatitis C virus outside hospital: evaluation of policy 2000-3

Problem Prophylactic treatment and follow-up after exposure to HIV, hepatitis B, and hepatitis C outside hospital needs to be improved.Background and setting Until January 2000, people in Amsterdam could report exposure outside hospital to either a hospital or the municipal health service. If they reported to the municipal health service, they were then referred to hospitals for HIV prophylaxis, whereas the municipal health service handled treatment and follow-up related to hepatitis B and hepatitis C and traced sources. For cases reported to a hospital, hospital staff often did not trace HIV sources or follow up patients for hepatitis B and hepatitis C.Key measures for improvement Providing adequate treatment for HIV, hepatitis B and hepatitis C after exposure for all reported exposures outside hospital.Strategies for change On 1 January 2000, a new protocol was introduced in which three Amsterdam hospitals and the municipal health service collaborated in the treatment and follow-up of exposures outside hospital. Both municipal health service and hospitals can decide whether HIV prophylaxis is necessary and prescribe accordingly. All people exposed in the community who report to hospitals are subsequently referred to the municipal health service for further treatment and follow-up.Effects of change The protocol is effective in that most people comply with treatment and follow-up. When indicated, HIV prophylaxis is started soon after exposure. In nearly two thirds of cases the municipal health service traced and tested the source.Lessons learnt Provision of treatment and follow-up in one place enables treatment, tracing and testing sources, and follow-up, including counselling and registration of all reported exposures in Amsterdam, which allows for swift identification of emerging epidemiological trends. Since May 2004 all Amsterdam hospitals have participated in the protocol.