Changes in sensitivity of human tumour cells to growth inhibition by proteinase inhibitors.

Inhibition of a cell-surface proteinase can inhibit the growth of many normal human cell types in culture. Some tumour cells are also sensitive to proteinase inhibitors, but others are resistant, and continue to grow in the presence of these inhibitors. Here we describe two human tumour cell lines which convert from the sensitive to the resistant state. In one case, the conversion occurs during routine passaging, but, in the other, it is determined by growth conditions, and is reversible.     

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

Recent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, lincRNA-p21 prevents reprogramming by sustaining H3K9me3 and/or CpG methylation at pluripotency gene promoters. Our results provide insight into the role of lncRNAs in reprogramming and establish a novel link between p53 and heterochromatin regulation.     

The Implementation of the Iterative Diagonalization Scheme and ab initio Molecular Dynamics Simulation with the LAPW Method

Abstract

A new ab initio molecular dynamics method based on the full-potential linearized-augmented-plane-wave (LAPW) basis set has been implemented. The LAPW basis set has been successfully employed for systems containing localized electrons such as first row atoms and transition metals. In our implementation of the LAPW-MD scheme, iterative residual minimization algorithm is used to solve the electronic states problem. The atoms are moved according to forces derived from the Hellman–Feynman theorem and incomplete basis set correction terms. The performance of the program is further enhanced by parallelization. We will discuss technical details of the program implementation and present results obtained from this code to the equilibrium structures and vibrational properties of simple diatomic molecules.     

Enrichment of fetal trophoblasts and nucleated erythrocytes from maternal blood by an immunomagnetic colloid system

The aim of this study was to isolate fetal trophoblasts and nucleated erythrocytes from maternal blood using the immunomagnetic colloid system. About 25 ml of maternal blood was collected from pregnant women between of 14 and 20 weeks gestation. Nucleated erythrocytes (NRBCs) were isolated from 5 ml of maternal blood and a nested polymerase chain reaction for the Y chromosome was used to determine fetal origin. The sensitivity of the fetal gender diagnosis was 80% and the specificity was 86%. Both fetal trophoblasts and NRBCs were isolated from the remaining 20 ml of maternal blood. The fetal gender of the trophoblast-enriched fraction was determined using fluorescence in situ hybridisation (FISH) with dual-colour XY-specific DNA probes. XY-specific signals were observed in 0.38% of cells sorted from all pregnant women carrying male fetuses (n = 10). Simultaneous immunophenotyping for the fetal haemoglobin and FISH using XY probes were used to evaluate the fetal origin of cells enriched with anti-CD71. The mean percentage of male fetal erythroblasts was 0.24% and the number of fetal erythroblasts was estimated to be about 672 in 20 ml of maternal blood. The number of fetal erythroblasts detected in our study was greater than that detected by most other separation techniques. Our study shows that it would be feasible to use the immunomagnetic colloid system for the isolation of both trophoblasts and NRBCs from the same maternal blood sample with relatively good efficiency. Received: 17 December 1998 / Accepted: 9 February 1999     

Cold acclimation increases physiological responsiveness to intraventricular injection of beta-endorphin in pentobarbital anaesthetized rats. 1. Cardiovascular functions

Intraventricular injection of beta-endorphin (3, 7, 10 and 30 nmol/kg) into the third ventricular of pentobarbital-anaesthetized male Sprague-Dawley rats resulted in a dose-dependent increase in mean arterial pressure (MAP) while injection of the same volume of 0.9% NaCl solution did not cause significant changes in MAP. Naloxone, which did not produce any significant change in MAP, antagonized the vasopressor effect of beta-endorphin, indicating that the response is mediated via the naloxone sensitive opiate receptors. Rats acclimated to cold (5 degrees) for 3 weeks showed a potentiated and prolonged increase in MAP following beta-endorphin injection, indicating an increased responsiveness to the peptide. This increased responsiveness in the cardiovascular system is probably of adaptive value in cold acclimation. Naloxone itself did not alter MAP either, but abolished the cardiovascular response to beta-endorphin completely in cold acclimated rats, indicating an increased effectiveness in its antagonistic effect following cold acclimation as well.