Neuron to glia signaling triggers myelin membrane exocytosis from endosomal storage sites

During vertebrate brain development, axons are enwrapped by myelin, an insulating membrane produced by oligodendrocytes. Neuron-derived signaling molecules are temporally and spatially required to coordinate oligodendrocyte differentiation. In this study, we show that neurons regulate myelin membrane trafficking in oligodendrocytes. In the absence of neurons, the major myelin membrane protein, the proteolipid protein (PLP), is internalized and stored in late endosomes/lysosomes (LEs/Ls) by a cholesterol-dependent and clathrin-independent endocytosis pathway that requires actin and the RhoA guanosine triphosphatase. Upon maturation, the rate of endocytosis is reduced, and a cAMP-dependent neuronal signal triggers the transport of PLP from LEs/Ls to the plasma membrane. These findings reveal a fundamental and novel role of LEs/Ls in oligodendrocytes: to store and release PLP in a regulated fashion. The release of myelin membrane from LEs/Ls by neuronal signals may represent a mechanism to control myelin membrane growth.     

Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression

Epidemiological and experimental observations support the hypothesis that chronic inflammation contributes to cancer development and progression; however, the mechanisms underlying the relationship between inflammation and cancer are poorly understood. To study these mechanisms, we have transfected the mouse 4T1 mammary carcinoma with the proinflammatory cytokine IL-1beta to produce a chronic inflammatory microenvironment at the tumor site. Mice with 4T1/IL-1beta tumors have a decreased survival time and elevated levels of immature splenic Gr1+CD11b+ myeloid-derived cells. These myeloid suppressor cells (MSC) are present in many patients with cancer and inhibit the activation of CD4+ and CD8+ T lymphocytes. 4T1/IL-1beta-induced MSC do not express the IL-1R, suggesting that the cytokine does not directly activate MSC. Neither T or B cells nor NKT cells are involved in the IL-1beta-induced increase of MSC because RAG2-/- mice and nude mice with 4T1/IL-1beta tumors also have elevated MSC levels. MSC levels remain elevated in mice inoculated with 4T1/IL-1beta even after the primary tumor is surgically removed, indicating that the IL-1beta effect is long lived. Collectively, these findings suggest that inflammation promotes malignancy via proinflammatory cytokines, such as IL-1beta, which enhance immune suppression through the induction of MSC, thereby counteracting immune surveillance and allowing the outgrowth and proliferation of malignant cells.     

Semiautomated enzymic micro methods for blood glucose and lactic acid on a single filtrate

Methods have been modified and adapted to permit enzymic automated micro analysis of glucose on 0.021 ml of blood, and of lactic acid on 0.0115 ml of blood. By means of a single 1:20 Somogyi filtrate with a final volume of 1–1.4 ml prepared from 0.1–0.15 ml blood, both determinations can be accomplished individually on the autoanalyzer.The range of concentrations of each method has been extended so that glucose may be determined between 5 and $\text{200 mg}\text{100 ml}$ (or higher depending on dilution) and lactic acid between 5 and $\text{125 mg}\text{100 ml}$.The methods are sensitive, reproducible, and stable. The recoveries and the comparison studies with manual methods are well within the limits of clinical investigation procdures.     

Structural and enzymatic properties of the AAA protein Drg1p from Saccharomyces cerevisiae. Decoupling of intracellular function from ATPase activity and hexamerization

The AAA protein Drg1 from yeast was affinity-purified, and its ATPase activity and hexamerization properties were analyzed. The same parameters were also determined for several mutant proteins and compared in light of the growth characteristics of the corresponding cells. The protein from a thermosensitive mutant exhibited reduced ATPase activity and hexamerization. These defects were not reversed by an intragenic suppressor mutation, although this allele supported growth at the nonpermissive temperature. A different set of mutants was generated by site-specific mutagenesis intended to adjust the Walker A box of the D2 domain of Drg1p to that of the D1 domain. A S562G exchange in D2 produced a nonfunctional protein that did not hexamerize but showed above-normal ATPase activity. The C561T mutant protein, on the other hand, was functional but hexamerized less readily and had reduced ATPase activity. In contrast, the C561T/S562G protein hexamerized less than wild type but had much higher ATPase activity. We distinguished strong and weak ATP-binding sites in the wild type protein but two weak sites in the C561T/S562G protein, indicating that the stronger site resides in D2. These observations are discussed in terms of the inter-relationship of ATPase activity per se, oligomeric status, and intracellular function for AAA proteins.     

Effect of administration of 5-hydroxytryptophan and an inhibitor ofl-aromatic amino acid decarboxylase on glucose metabolism in rat brain

The effect of 5-hydroxytryptophan (5-HTP)—the precursor of serotonin (5-hydroxytryptamine, 5-HT)—and of an inhibitor,N-(dl-seryl)-N-(2,3,4-trihydroxybenzyl)hydrazine (Ro4-4602), ofl-aromatic amino acid decarboxylase on the metabolism of glucose to amino acids in brain tissue was investigated. Labeled glucose (20 Ci, 0.24 mg in 0.2 ml 0.9% saline) was injected intravenously into fed rats pretreated with Ro4-4602 (50 mg/kg intraperitoneally) either alone or in combination with 5-HTP (30 mg/kg intravenously) or with the appropriate vehicle. After the injection of Ro4-4602 plus 5-HTP, the concentrations of 5-HT and 5-HTP in brain were increased, but the increase of 5-HTP that Ro4-4602 slightly inhibits the reaction of decarboxylation in the brain, although at the dose used the drug is usually considered to act only peripherally. After administration of Ro4-4602 alone or combined with 5-HTP, the concentration of glucose in plasma was not significantly increased. However, the concentration of glucose in brain was markedly increased with such treatments. The administration of Ro4-4602 alone or combined with 5-HTP reduced the flux of¹⁴C from labeled glucose to amino acids in brain. The concentrations of amino acids in brain were little changed by these treatments.     

The john innes composts: Some effects of increasing the base-fertiliser concentration on the growth and composition of the tomato

Summary The effects of increasing the strength of the base fertiliser in John Innes composts on the rates of growth, development, and the chemical composition of tomato Potentate, and also on the levels of available nutrients within the composts, has been examined. Comparison has also been made between plants grown in the JIP1, JIP2, and JIP3, composts and those grown in sand cultures receiving Hoagland's nutrient solution at each irrigation.For an initial period after pricking out an inverse relation between plant-growth rate and base-fertiliser concentration was found. This was later changed to a positive relationship. A significant interaction was shown between the length of the initial period during which the growth rate was depressed due to fertiliser concentration and the light intensity.The high rate of base-fertiliser application did not however extend the period of high growth rate or significantly reduce the rate of the fall in the nitrogen concentration within the plant. It is conlcuded that, from a practical point of view, plants grown in all three strength composts will require supplementary feeding at the same period.Whilst approximately 75 per cent of the ammonia extracted by Morgan's solvent was also water soluble this form of nitrogen did not significantly influence the specific conductivity of saturated extracts. Nitrates were highly correlated with the specific conductance.     

Über Musterbildung in der Rhizodermis und Exodermis bei einigen Angiospermen und einer Polypodiacee

Ohne Zusammenfassung     

Effect of Arginine-deficient Media on the Herpes-Type Virus Associated with Cultured Burkitt Tumor Cells

After incubation at 37 C for 2 or more days, Basal Medium Eagle (BME) supplemented with 25% fetal calf serum (FCS) was not able to support adequate growth of EB3 and other lines of Burkitt tumor cells. The medium did, however, increase, by a factor of about 10, the number of cells synthesizing herpes-type virus with which the cultures were persistently infected. Not every lot of FCS produced these effects, nor were these effects seen when BME and FCS were incubated separately for 7 days before the medium was completed. At 37 C, appropriate lots of FCS interacted with several of the amino acids present in BME; this interaction resulted in an inhibition of cellular growth, whereas interaction with arginine yielded the virus-enhancing effect. Arginine-free BME, supplemented with 25% FCS and used without prior incubation, prevented cellular replication and promoted viral infection to a similar extent as did preincubated complete medium. Replenishment of arginine reduced, but did not regularly abolish, the virus-enhancing activity of preincubated media. RPMI-1629 medium was less affected by preincubation with FCS because it contained twice the amount of arginine that BME contained. The FCS factors which act upon arginine and other amino acids are not dialyzable and are partially resistant to heating at 56 or 60 C for 30 to 60 min. Calf and horse sera appear to be devoid of these activities. The nature of these interactions, as well as the mechanism by which arginine deficiency enhanced the viral infection, remains to be ascertained.