Cellobiose metabolism in Erwinia: genetic study

Summary The study of mutants of Erwinia specifically unable to ferment cellobiose indicates that the mutations are clustered between arg and ile on the chromosome of this organism. In vivo cloning of the genes responsible for cellobiose utilization lead to a plasmid, pBEC2, which complements all Erwinia Clb^- specific mutants. When introduced into wild-type E. coli it allows this organism to use cellobiose, arbutin and salicin; it also complements bglB and bglC mutants of Escherichia coli indicating that arbutin and salicin utilization is due to the products of the pBEC2 cloned genes. From the characterization of mutants pleiotropically affected in the utilization of various carbon sources, including cellobiose, arbutin and salicin, it is proposed that the three--glucosides are substrates of the phosphoenolpyruvate-dependent phosphotransferase system (PTS).     

Hydrolysis of bradykinin and its higher homologues by angiotensin-converting enzyme (Short Communication)

The hydrolysis of bradykinin and its higher homologues by angiotensin-converting enzyme has been investigated by using an automated ninhydrin technique. The results show an inverse relationship of hydrolysis rate with size and charge of the peptide, which parallels the inactivation in the pulmonary circulation and offers an explanation for the selectivity of metabolism of these kinins by the lungs.     

Un cas de mosaïcisme avec grand chromosome surnuméraire

Sans résuméRecherches effectuées avec l'appui du Fonds de la Recherche Scientifique Médicale et du Fonds de la Recherche Fondamentale Collective (Belgique).     

Inputs from upper airway affect firing of respiratory-associated midbrain neurons

Chen, Zibin, and Frederic L. Eldridge. Inputs fromupper airway affect firing of respiratory-associated midbrain neurons. J. Appl. Physiol. 83(1): 196-203, 1997.In 16 decerebrated unanesthetized cats, we studied effects ofneural inputs from upper airway on firing of 62 mesencephalic neuronsthat also developed respiratory-associated (RA) rhythmic firing whenrespiratory drive was high [Z. Chen, F. L. Eldridge, and P.G.Wagner. J. Physiol. (Lond.) 437:305-325, 1991] and on firing of 16 neurons that did notdevelop the rhythmic firing (non-RA neurons). Activity in RA neuronsincreased after mechanical expansion of pharynx (45% of those tested)or larynx (68%) and after stimulation of glossopharyngeal (50%) orsuperior laryngeal nerves (77%). The increased neuronal firingoccurred despite decreases or abolition of respiratory activity(expressed in phrenic nerve). Neuronal firing also increased aftermechanical stimulation of nasal mucosa (66%) or by jetsof air directed into the nares (48%) and after lightbrushing of nasal skin (~40%). Most stimuli led to decreased firingin a smaller number of neurons, and some neurons showed no response.None of the non-RA neurons developed an increase of firing after any ofthe stimuli, although one had decreased firing after stimulation of thesuperior laryngeal nerve. We conclude that inputs from the upper airwayand nasal skin have independent modulatory effects on the samemesencephalic neurons that are stimulated by ascending rhythmic RAinput from the medulla. These findings may have relevance to generationof the sensation of dyspnea.

     

Response of lake phytoplankton communities to in situ manipulations of light intensity and colour

Phytoplankton preferences for light intensity and colour weredetermined in field experiments using coloured plexiglass cubessuspended at different depths in Heney Lake, Québec.Diatoms and green algae favoured intensities greater than 1%I_o (surface irradiance) contrary to dinoflagellates and otherflagellates that preferred lower intensity. Red radiation usuallyincreased the relative proportion of blue-greens, diatoms andgreen algae, whereas it reduced that of dinoflageilates. Wepropose that differential utilization of the light gradientallows certain phytoplankton taxa to partition the water column,thereby reducing potential competition. This is supported bythe general agreement between our findings and the known depthdistribution of algae in lakes.     

Alteration by methadone of catecholamine uptake and release in isolated rat adrenomedullary storage vesicles

Incubation of isolated rat adrenomedullary storage vesicles with methadone produced inhibition of ³H-epinephrine uptake and promotion of release of endogenous catecholamines. Neither effect was seen using morphine, nor could morphine antagonize methadone-induced catecholamine release, suggesting that these actions are not mediated by opiate receptors. Inhibition of uptake by methadone appeared to contain a competitive component with a lower Ki for methadone compared to the Km for ³H-epinephrine. Despite competitive inhibition by methadone, the maximal uptake capacity (analogous to Vmax) as determined by double-reciprocal plots, was increased by the drug, probably as a result of greater availability of intravesicular storage sites because of the drug-induced of release endogenous catecholamines. Agents which enhance or block catecholamine transport into vehicles had no effect on the catecholamine release by methadone, indicating that the latter is separable from the action on uptake. These alterations of catecholamine uptake and release may play a role in the effects of methadone on the adrenal medulla $\text{in vivo}$.     

Cell-penetrating peptides: from molecular mechanisms to therapeutics

The recent discovery of new potent therapeutic molecules which do not reach the clinic due to poor delivery and low bioavailability have made the delivery of molecules a keystone in therapeutic development. Several technologies have been designed to improve cellular uptake of therapeutic molecules, including CPPs (cell-penetrating peptides), which represent a new and innovative concept to bypass the problem of bioavailability of drugs. CPPs constitute very promising tools and have been successfully applied for in vivo. Two CPP strategies have been described to date; the first one requires chemical linkage between the drug and the carrier for cellular drug internalization, and the second is based on the formation of stable complexes with drugs, depending on their chemical nature. The Pep and MPG families are short amphipathic peptides, which form stable nanoparticles with proteins and nucleic acids respectively. MPG- and Pep-based nanoparticles enter cells independently of the endosomal pathway and efficiently deliver cargoes, in a fully biologically active form, into a large variety of cell lines, as well as in animal models. This review focuses on the structure-function relationship of non-covalent MPG and Pep-1 strategies, and their requirement for cellular uptake of biomolecules and applications in cultured cells and animal models.     

Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice

The liver secretes triglyceride-rich VLDLs, and the triglycerides in these particles are taken up by peripheral tissues, mainly heart, skeletal muscle, and adipose tissue. Blocking hepatic VLDL secretion interferes with the delivery of liver-derived triglycerides to peripheral tissues and results in an accumulation of triglycerides in the liver. However, it is unclear how interfering with hepatic triglyceride secretion affects adiposity, muscle triglyceride stores, and insulin sensitivity. To explore these issues, we examined mice that cannot secrete VLDL [due to the absence of microsomal triglyceride transfer protein (Mttp) in the liver]. These mice exhibit markedly reduced levels of apolipoprotein B-100 in the plasma, along with reduced levels of triglycerides in the plasma. Despite the low plasma triglyceride levels, triglyceride levels in skeletal muscle were unaffected. Adiposity and adipose tissue triglyceride synthesis rates were also normal, and body weight curves were unaffected. Even though the blockade of VLDL secretion caused hepatic steatosis accompanied by increased ceramides and diacylglycerols in the liver, the mice exhibited normal glucose tolerance and were sensitive to insulin at the whole-body level, as judged by hyperinsulinemic euglycemic clamp studies. Normal hepatic glucose production and insulin signaling were also maintained in the fatty liver induced by Mttp deletion. Thus, blocking VLDL secretion causes hepatic steatosis without insulin resistance, and there is little effect on muscle triglyceride stores or adiposity.