CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR

Centromere-binding protein B (CENP-B) is a widely conserved DNA binding factor associated with heterochromatin and centromeric satellite repeats. In fission yeast, CENP-B homologues have been shown to silence long terminal repeat (LTR) retrotransposons by recruiting histone deacetylases. However, CENP-B factors also have unexplained roles in DNA replication. Here we show that a molecular function of CENP-B is to promote replication-fork progression through the LTR. Mutants have increased genomic instability caused by replication-fork blockage that depends on the DNA binding factor switch-activating protein 1 (Sap1), which is directly recruited by the LTR. The loss of Sap1-dependent barrier activity allows the unhindered progression of the replication fork, but results in rearrangements deleterious to the retrotransposon. We conclude that retrotransposons influence replication polarity through recruitment of Sap1 and transposition near replication-fork blocks, whereas CENP-B counteracts this activity and promotes fork stability. Our results may account for the role of LTR in fragile sites, and for the association of CENP-B with pericentromeric heterochromatin and tandem satellite repeats.     

A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies

Mitochondrial encephalomyopathies are usually divided into three distinct clinical subgroups: (1) mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS); (2) myoclonus epilepsy associated with ragged-red fibres (MERRF); and (3) chronic progressive external ophthalmoplegia (CPEO) including Kearns-Sayre syndrome. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNA(Leu)(UUR) that is specific to patients with MELAS. Because this mutation creates an ApaI restriction site, we could perform a simple molecular diagnostic test for the disease. The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested. Southern blot analysis confirmed that the mutant DNA always coexists with the wild-type DNA (heteroplasmy).     

Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor

Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.     

Cell cycle progression by the repression of primary cilia formation in proliferating cells

In most cell types, primary cilia protrude from the cell surface and act as major hubs for cell signaling, cell differentiation, and cell polarity. With the exception of some cells ciliated during cell proliferation, most cells begin to disassemble their primary cilia at cell cycle re-entry. Although the role of primary cilia disassembly on cell cycle progression is still under debate, recent data have emerged to support the idea that primary cilia exert influence on cell cycle progression. In this review, we emphasize a non-mitotic role of Aurora-A not only in the ciliary resorption at cell cycle re-entry but also in continuous suppression of cilia regeneration during cell proliferation. We also summarize recent new findings indicating that forced induction/suppression of primary cilia can affect cell cycle progression, in particular the transition from G0/G1 to S phase. In addition, we speculate how (de)ciliation affects cell cycle progression.     

Plasma adenosine concentrations are elevated in Dahl salt-sensitive rats

We measured plasma levels of adenosine in Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) to examine the potential role of adenosine in cardiovascular regulation in this type of hypertension. Plasma adenosine concentrations were significantly higher in DS than in DR. The NaCl content in the diet did not affect plasma adenosine concentration in either DS or DR. Significant positive correlation was found between adenosine concentrations and systolic blood pressure when the data for DS and DR were analyzed together. These results suggest that adenosine may play an important role in the pathophysiology of hypertension in DS.     

C fibre innervation of a mechanoreceptor

Zusammenfassung Pacinische Körperchen besitzen eine doppelte Innervation. Ausser der bekannten markhaltigen mechanorezeptorischen Faser (A-Faser, Übertragungsgeschwindigïeit 35 m/sec) tritt noch eine feine marklose Faser (C-Faser) in das Körperchen ein. Die C-Faser lässt sich mit elektrophysiologischen und histologischen Methoden in den mesenteralen Nerven, im Stiel des Pacinischen Körperchens sowie in seinem Innern (Proximalsegment) nachweisen.     

Dissociation of digoxin-like immunoreactivity and Na+,K+-ATPase inhibitory activity in rat plasma

We measured endogenous digitalis-like factor (EDF) in rat plasma during acute saline infusion by two different procedures. Na+,K+-ATPase inhibitory activity in the rat plasma significantly increased during saline loading (7.8 +/- 2.2 vs 2.5 +/- 0.9%, with and without acute saline loading, respectively, p less than 0.05). On the other hand, the plasma digoxin-like immunoreactivity significantly decreased during acute saline loading (16.9 +/- 1.6 vs 32.0 +/- 2.8 pg digoxin equivalents/ml, with and without acute saline loading, respectively, p less than 0.01). These results indicate that the major substances detected by digoxin-like immunoreactivity and direct Na+,K+-ATPase inhibitory activity are completely different, at least in rat plasma.     

Implementation of 3-Valued Paraconsistent Logic Programming Towards Decision Making System of Agents

Due to the rapid development of applications of artificial intelligence and robotics in recent years, the necessity of reasoning and decision making with uncertain and inaccurate information is increasing. Since robots in the real world are always exposed to behavioral inaccuracies and uncertainty arising from recognition methods, they may occasionally encounter contradictory facts during reasoning on action decision.Paraconsistent logic programming is promising to make appropriate action decisions even when an agent is exposed to such uncertain information or contradictory facts, but there has been no implementation of this programming to the best of our knowledge. We propose a resolution algorithm for the 3-valued paraconsistent logic programming system QMPT0 and its implementation on SWI-Prolog. We also describe an application of the 3-valued paraconsistent logic programming regarding agent decision making.