Movements and associations of ribosomal subunits in a secretory cell during growth inhibition by starvation

In Chironomus tentans salivary gland cells, the cytoplasm can be dissected into concentric zones situated at increasing distances from the nuclear envelope. After RNA labeling, the newly made ribosomal subunits are found in the cytoplasm mainly in the neighborhood of the nucleus with a gradient of increasing abundance towards the periphery of the cell. The gradient for the small subunit lasts for a few hours and disappears entirely after treatment with puromycin. The large subunit also forms a gradient but one which is only partially abolished by puromycin. The residual gradient which which is resistant to the addition of the drug is probably due to the binding of some large ribosomal units to the membranes of the endoplasmic reticulum (J.-E. Edstrom and u. Lonn. 1976. J. Cell Biol. 70:562-572, and U. Lonn and J.-E. Edstrom. 1976. J. Cell. Biol. 70:573-580). If growth is inhibited by starvation, only the puromycin-sensitive type gradient is observed for the large subunit, suggesting that the attachment of these newly made subunits to the endoplasmic reticulum membranes will not occur. If, on the other hand, the drug-resistant gradient is allowed to form in feeding animals, it is conserved during a subsequent starvation for longer periods than in control feeding animals. This observation provides a further support for an effect of starvation on the normal turnover of the large subunits associated with the endoplasmic reticulum. These results also indicate a considerable structural stability in the cytoplasm of these cells worth little or no gross redistribution of cytoplasmic structures over a period of at least 6 days.     

Inactivation by ammonia of the photosynthetic reduction of nitrate in Nostoc muscorum particles.

Ammonia, as well as other uncouplers of photophosphorylation, strongly inhibit the photosynthetic reduction of nitrate by particles of the blue-green alga Nostoc muscorum. The enzyme responsible for nitrate reduction, nitrate reductase, can be reversibly inactivated by reduction in a ferredoxin-dependent reaction. Nitrate protects against this inactivation, and molecular oxygen restores the original activity.     

Substrate selectivity of squalene synthetase.

Six 1-3H-labeled analogues of farnesyl pyrophosphate have been studied as potential substrates for yeast and rat liver squalene synthetases: 2-methylfarnesyl pyrophosphate (4), 3-demethylfarnesyl pyrophosphate (5), 7,11-dimethyl-3-ethyl-2,6,10-dodecatrienyl pyrophosphate (6), 6,7,10,11-tetrahydrofarnesyl pyrophosphate (7), 4-methylthiofarnesyl pyrophosphate (8), and 4-fluorofarnesyl pyrophosphate (9). Analogues 4 and 5 are enzymatically incorporated into 11-methylsqualene (10) and 10-demethylsqualene (11), respectively, even if no farnesyl pyrophosphate is added to the incubations. None of the other analogues gives nonpolar products with either the yeast or liver enzymes. No tritium is enzymatically released to the medium from any of the analogues, indicating that they are not accepted at the first (proton exchanging) site. The data rule out formation of dead-end presqualene pyrophosphate products with analogues as first, but not as second, substrates. Implications of these results for the enzyme active-site topology and mechanism are discussed.     

Statistical-mechanical theory of passive transport through partially sieving or leaky membranes

The basic equations for multicomponent transport through partially sieving or leaky membranes are discussed from a statistical-mechanical viewpoint. They have the same mathematical form as the corresponding equations for open membranes, but differ in a discontinuous way from the equations for semipermeable membranes (since a "leak" in a semipermeable membrane constitutes a discontinuous or singular perturbation). Partially sieving membranes can be made to mimic semipermeable behavior through the introduction of characteristic time scales. They may approximate semipermeable behavior at short times, but always deviate at longer times.     

Wiedemann-Beckwith syndrome: clinical, cytogenetical and radiological observations in 39 new cases.

Thirty-nine patients (82% under 1 year of age) with Wiedemann-Beckwith syndrome (WBS) were prospectively studied. To evaluate the somatometric data the normal range was set out at mean +/- 2 SD. The relevant physical findings were a characteristic face, non increased mean height and weight, normal head circumference, defective abdominal wall, a predominance of the upper segment, and tibial bowing. Mental retardation was documented in 5 cases but in only 1 it was related to hypoglycemia. The 32 cases karyotyped were normal. Since neonatal hypoglycemia is frequent (34.3% in our series) and potentially deleterious for the CNS we propose to monitor the glycemia every 6 h during the first 3 days in WBS newborns in order to correct glycemia below of 2.6 mmol/l (46.8 mg/dl) according to recent studies. The comparison with previous large series enabled us to precise the frequency, onset and evolution of the main stigmata.     

Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6

Endotoxin (LPS) at sublethal doses injected i.v. into rats was found to induce IL-6 mRNA expression peaking at 1 to 2 h in whole organ RNA preparations of the spleen, liver, lung, bowel, and kidney. IL-6 serum protein levels also peaked at 2 h. TNF and IL-1, generally considered to be among the most rapidly released cytokines, also induced IL-6 expression. IL-6 in turn inhibited TNF and IL-1 expression, suggesting that IL-6 may be part of a negative feedback mechanism in the cytokine cascade. Dexamethasone down-regulated and Corynebacterium parvum up-regulated IL-6 expression, although the possibility cannot be excluded that these immunomodulating factors may in part have exerted their effects indirectly via the up- and down-regulation of TNF and IL-1. IL-6 injected i.v. at a pathophysiologically relevant dose caused a peripheral neutrophilia and mild myeloproliferative effect in the bone marrow.     

Reconstitution of sodium channels in large liposomes formed by the addition of acidic phospholipids and freeze-thaw sonication

Phosphatidylcholine (PC) alone or with phosphatidylethanolamine (PE) are sufficient for the reconstitution of Na+ channels in planar lipid bilayers. However, when Na+ channels were first reconstituted into liposomes using the freeze-thaw-sonication method, addition of acidic phospholipids, such as phosphatidylserine (PS), to the neutral phospholipids was necessary to obtain a significant toxin-modulated 22Na uptake. To further investigate the acidic phospholipid effect on reconstitution into liposomes, Na+ channels purified from Electrophorus electricus electrocytes were reconstituted into liposomes of different composition by freeze-thaw sonication and the effect of batrachotoxin and tetrodotoxin on the 22Na flux was measured. The results revealed that, under our experimental conditions, the presence of an acidic phospholipid was also necessary to obtain a significant neurotoxin-modulated 22Na influx. Though neurotoxin-modulated 22Na fluxes have been reported in proteoliposomes made with purified Na+ channels and PC alone, the 22Na fluxes were smaller than those found using lipid mixtures containing acidic phospholipids. Electron microscopy of negatively stained proteoliposomes prepared with PC, PC/PS (1:1 molar ratio), and PS revealed that the acidic phospholipid increases the size of the reconstituted proteoliposomes. The increment in size caused by the acidic phospholipid, due to the associated increase in internal volume for 22Na uptake and in area for Na+ channel incorporation, appears to be responsible for the large neurotoxin-modulated 22Na fluxes observed.     

Organic calcium channel blockers generate the coexistence of two different types of action potentials in the same muscle membrane following chemical induction of excitability.

1. Following exposure to the sulfhydryl reagents known as alpha,beta-unsaturated carbonyl compounds, the ventroabdominal flexor muscles of the crustacean Atya lanipes, which are normally completely inexcitable, generate trains of overshooting calcium action potentials; the effects of organic calcium channel antagonists and potassium channel blockers on the chemically-induced trains of action potentials have been studied. 2. Verapamil and D600, at micromolar concentrations, elicit the appearance of slow, cardiac-like action potentials which coexist with the much faster chemically-induced calcium spikes, transforming the regular repetitive firing into a cyclic bursting pattern. 3. Bepridil (1 microM) decreases the frequency of firing of the action potentials, probably by increasing the threshold for the activation of a population of the chemically-induced calcium channels. 4. The potassium channel blockers, TEA (30-40 mM) and quinidine (100-200 microM), delayed the rate of repolarization of the chemically-induced action potentials; none of the potassium channel blockers, however, induced the appearance of repetitive spike activity.