Apoptotic cell-derived factors induce arginase II expression in murine macrophages by activating ERK5/CREB

Apoptotic cell (AC)-derived factors alter the physiology of macrophages (MΦs) towards a regulatory phenotype, characterized by reduced nitric oxide (NO) production. Impaired NO formation in response to AC-conditioned medium (CM) was facilitated by arginase II (ARG II) expression, which competes with inducible NO synthase for l-arginine. Here we explored signaling pathways allowing CM to upregulate ARG II in RAW264.7 MΦs. Sphingosine-1-phosphate (S1P) was required and acted synergistically with a so far unidentified factor to elicit high ARG II expression. S1P activated S1P₂, since S1P₂ knockdown prevented ARG II upregulation. Furthermore, ERK5 knockdown attenuated CM-mediated ARG II protein induction. CREB was implicated as shown by EMSA analysis and decoy-oligonucleotides scavenging CREB in RAW264.7 MΦs, which blocked ARG II expression. We conclude that AC-derived S1P binds to S1P₂ and acts synergistically with other factors to activate ERK5 and concomitantly CREB. This signaling cascade shapes an anti-inflammatory MΦ phenotype by ARG II induction.     

Modulation of connexin signaling by bacterial pathogens and their toxins

Inherent to their pivotal tasks in the maintenance of cellular homeostasis, gap junctions, connexin hemichannels, and pannexin hemichannels are frequently involved in the dysregulation of this critical balance. The present paper specifically focuses on their roles in bacterial infection and disease. In particular, the reported biological outcome of clinically important bacteria including Escherichia coli, Shigella flexneri, Yersinia enterocolitica, Helicobacter pylori, Bordetella pertussis, Aggregatibacter actinomycetemcomitans, Pseudomonas aeruginosa, Citrobacter rodentium, Clostridium species, Streptococcus pneumoniae, and Staphylococcus aureus and their toxic products on connexin- and pannexin-related signaling in host cells is reviewed. Particular attention is paid to the underlying molecular mechanisms of these effects as well as to the actual biological relevance of these findings.     

Soviet psychiatry: pre-emptive resignation?

The Soviet All-Union Society of Neurologists and Psychiatrists has resigned from the World Psychiatric Association (WPA). The resignation was not unexpected in the face of a growing move by Western psychiatric associations to expel the Soviet society because of its refusal to cooperate with the WPA's committee to monitor political misuse of psychiatry.     

Internees in Poland: psychiatric abuse claim

The World Psychiatric Association has been asked to intervene on behalf of four Polish internees who are claiming to be victims of psychiatric repression for political reasons. Under martial law, Poland's security forces have shown a renewed interest in psychiatric internment of disruptive persons.     

Sur l'interaction entre aldéhydes ou réductones et acides aminés ou protéines

Summary Proteins were exposed to acetaldehyde vapour or mixed with glucose in solution and the basic groups determined by their dy binding capacity. Only serum albumin shows a marked decrease of basic groups and of the carbon/nitrogen ratio as a sign of condensation of aldehyde and amine groups. These results were corroborated by the direct estimation of the aldehyde resine formed on the protein: serum albumin and fibrin treated with acetaldehyde vapour contained 5 to 10 times more resin than the other proteins examined. No rapid combination between serum proteins and glucose could be demonstrated by the dy method or by the kinetics of change of pH. The slow reaction seems not to be dependent on denaturation.     

Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome)

Johanson-Blizzard syndrome (OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. We mapped the disease-associated locus to chromosome 15q14-21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson-Blizzard syndrome. UBR1 encodes one of at least four functionally overlapping E3 ubiquitin ligases of the N-end rule pathway, a conserved proteolytic system whose substrates include proteins with destabilizing N-terminal residues. Pancreas of individuals with Johanson-Blizzard syndrome did not express UBR1 and had intrauterine-onset destructive pancreatitis. In addition, we found that Ubr1(-/-) mice, whose previously reported phenotypes include reduced weight and behavioral abnormalities, had an exocrine pancreatic insufficiency, with impaired stimulus-secretion coupling and increased susceptibility to pancreatic injury. Our findings indicate that deficiency of UBR1 perturbs the pancreas' acinar cells and other organs, presumably owing to metabolic stabilization of specific substrates of the N-end rule pathway.     

The formation of a massive protostar through the disk accretion of gas

The formation of low-mass stars like our Sun can be explained by the gravitational collapse of a molecular cloud fragment into a protostellar core and the subsequent accretion of gas and dust from the surrounding interstellar medium. Theoretical considerations suggest that the radiation pressure from the protostar on the in-falling material may prevent the formation of stars above ten solar masses through this mechanism, although some calculations have claimed that stars up to 40 solar masses can in principle be formed via accretion through a disk. Given this uncertainty and the fact that most massive stars are born in dense clusters, it was suggested that high-mass stars are the result of the runaway merging of intermediate-mass stars. Here we report observations that clearly show a massive star being born from a large rotating accretion disk. The protostar has already assembled about 20 solar masses, and the accretion process is still going on. The gas reservoir of the circumstellar disk contains at least 100 solar masses of additional gas, providing sufficient fuel for substantial further growth of the forming star.     

A tunable carbon nanotube electromechanical oscillator

Nanoelectromechanical systems (NEMS) hold promise for a number of scientific and technological applications. In particular, NEMS oscillators have been proposed for use in ultrasensitive mass detection, radio-frequency signal processing, and as a model system for exploring quantum phenomena in macroscopic systems. Perhaps the ultimate material for these applications is a carbon nanotube. They are the stiffest material known, have low density, ultrasmall cross-sections and can be defect-free. Equally important, a nanotube can act as a transistor and thus may be able to sense its own motion. In spite of this great promise, a room-temperature, self-detecting nanotube oscillator has not been realized, although some progress has been made. Here we report the electrical actuation and detection of the guitar-string-like oscillation modes of doubly clamped nanotube oscillators. We show that the resonance frequency can be widely tuned and that the devices can be used to transduce very small forces.