D-glucosamine propanedithioacetal, an efficient chiral auxiliary in beta-lactam chemistry.

The synthesis of some monocyclic beta-lactams (monobactams) by the Staudinger reaction using D-glucosamine propanedithioacetal as chiral auxiliary is reported. The influence of several radicals at C3, C4, and C1' (sugar moiety) as well as other structural aspects are considered in relation to the antielastase activity.     

Cytochemical localization of alkaline phosphatase and ouabain-sensitive K+-dependent p-nitrophenylphosphatase activities in brain capillaries of the newt

The ultrastructural localization of alkaline phosphatase and K+-NPPase was investigated in brain capillaries of newt by a cytochemical study using whole brain perfusion. The alkaline phosphatase activity was present in both luminal and antiluminal membranes of the endothelial cells. By contrast, the K+-NPPase was located only in antiluminal membranes of the brain capillaries. This distinct enzymatic distribution suggested that the luminal and antiluminal membranes are functionally different. The role of alkaline phosphatase and K+-NPPase in the blood brain barrier is discussed.     

Acute effects of insulin and glucagon on hepatic casein kinase 2 in adult fed rats: correlation of the effects on casein kinase 2 with the changes in glycogen synthase activity

Administration of insulin to adult fed rats caused an inactivation of hepatic casein kinase 2 as determined by the decrease in the activity ratio measured at a low (0.1 mg/ml) and a high (1.0 mg/ml) concentration of beta-casein. Maximal inactivation occurred 45 min after injection and the dose for half-maximal effect was 44 micrograms/kg. The effect of insulin was due to an increase in the apparent Km value for the protein substrate but the magnitude of the effect depended on the substrate used, decreasing in the order beta-casein greater than glycogen synthase much greater than whole casein. The activation of casein kinase 2 by glucagon (M. Pérez, J. Grande, and E. Itarte (1988) FEBS Lett. 238, 273-276) was also more marked with beta-casein and glycogen synthase than with whole casein. A good correlation was observed between the time- and dose-dependent activation of glycogen synthase and inactivation of casein kinase 2 promoted by insulin. Similarly, the inactivation of glycogen synthase by glucagon correlated with the activation of casein kinase 2 caused by this hormone. The possible involvement of casein kinase 2 on the mechanism(s) through which these hormones control hepatic glycogen synthase is discussed.     

Amphetamine and chlorpromazine modify cerebral insulin levels in rats

Rats treated with chlorpromazine (CPZ) (1 mg/kg/day i.p.) experienced a marked decline in cerebral insulin levels (0.057 +/- 0.01 ng/g wet weight) with respect to a control group (0.38 +/- 0.05 ng/g wet weight), while rats given D-amphetamine bitartrate (AMPH) chronically (20 mg/kg/day p.o.) showed a rise in cerebral insulin (0.55 +/- 0.04 ng/g wet weight). Combined treatment with both drugs at the same dosages produced lower cerebral insulin levels (0.46 +/- 0.10 ng/g wet weight) than in the AMPH animals. In the groups of rats treated with CPZ and with AMPH + CPZ, there was a slight elevation in serum insulin levels. Serum glucose values did not vary.     

A comparison of net and gross rates of oxygen production as a function of light intensity in some natural plankton populations and in a Synechococcus culture

In vitrorates of gross and net oxygen production were measuredas a function of light intensity in some plankton communitiescollected from Bedford Basin, Nova Scotia, and in a monoclonalculture of Synechococcus. The rate of gross oxygen productionwas measured by a technique in which the stable oxygen isotope,¹⁸O, serves as a photosynthetic tracer Net oxygen productionwas measured by automated Winkler technique. The rate of communityrespiration in the light was then determined by the differencebetween gross and net rates of oxygen production. In the naturalpopulations examined, neither gross nor net oxygen productionrates were significantly inhibited at the highest light intensitymeasured (500–800 µE m^–2 s^–1) In a samplein which the dark respiration rate was small relative to themaximal rate of production [P_max;sensu Platt et al (1980) JMar. Res., 38, 687–701] the rates of ‘light’respiration were 3 times greater. In two other communities,with high rates of dark respiration relative to P_maxthe ratesof ‘light’ respiration were closer to rates of darkrespiration. In the Synechococcus clone, both gross and netoxygen production rates were inhibited at high light intensities.Rates of ‘light’ respiration were found to varyas a function of light intensity. The greatest rates of respirationwere measured in samples incubated at light intensities thatwere just saturating (100 µE m^–2 s^–1). Therates of ¹⁴C production were also measured as a function oflight intensity The photosynthetic quotients, based on ¹⁴C productionrates and gross oxygen production rates, average 1 9     

Kinetic properties of hydrogenase isolated from Desulfovibrio vulgaris (Hildenborough)

Hydrogenase of Desulfovibrio vulgaris shows nonlinear kinetics in hydrogen production with both the natural electron carrier, cytochrome c3, and the artificial donor, methyl viologen semiquinone. Increasing concentrations of salt progressively inhibit the hydrogen production, as do increasing amounts of dimethylsulfoxide (Me2SO). Hydrogen consumption activity does not change up to 30% (v/v) of Me2SO. Preincubation in Me2SO up to 55% (v/v) does not affect the hydrogen uptake or production. The production activity of the enzyme shows an optimum around pH 6. When plotted as a function of redox potential the activity can be fitted to a Nernst equation with n = 1. Midpoint potentials calculated at various values follow approximately the hydrogen electrode to pH 6. Thereafter, there is a shift of about 40 mV to higher redox potentials.     

Localization of sequences regulating ancestral and acquired sites of esterase6 activity in Drosophila melanogaster

We have broadly defined the DNA regions regulating esterase6 activity in several life stages and tissue types of D. melanogaster using P- element-mediated transformation of constructs that contain the esterase6 coding region and deletions or substitutions in 5' or 3' flanking DNA. Hemolymph is a conserved ancestral site of EST6 activity in Drosophila and the primary sequences regulating its activity lie between -171 and -25 bp relative to the translation initiation site: deletion of these sequences decrease activity approximately 20-fold. Hemolymph activity is also modulated by four other DNA regions, three of which lie 5' and one of which lies 3' of the coding region. Of these, two have positive and two have negative effects, each of approximately twofold. Esterase6 activity is present also in two male reproductive tract tissues; the ejaculatory bulb, which is another ancestral activity site, and the ejaculatory duct, which is a recently acquired site within the melanogaster species subgroup. Activities in these tissues are at least in part independently regulated: activity in the ejaculatory bulb is conferred by sequences between -273 and -172 bp (threefold decrease when deleted), while activity in the ejaculatory duct is conferred by more distal sequences between -844 and -614 bp (fourfold decrease when deleted). The reproductive tract activity is further modulated by two additional DNA regions, one in 5' DNA (-613 to -284 bp; threefold decrease when deleted) and the other in 3' DNA (+1860 to +2731 bp; threefold decrease when deleted) that probably overlaps the adjacent esteraseP gene. Collating these data with previous studies suggests that expression of EST6 in the ancestral sites is mainly regulated by conserved proximal sequences while more variable distal sequences regulate expression in the acquired ejaculatory duct site.      

Phylogenetic diversification of immunoglobulin genes and the antibody repertoire

Immunoglobulins are encoded by a large multigene system that undergoes somatic rearrangement and additional genetic change during the development of immunoglobulin-producing cells. Inducible antibody and antibody-like responses are found in all vertebrates. However, immunoglobulin possessing disulfide-bonded heavy and light chains and domain-type organization has been described only in representatives of the jawed vertebrates. High degrees of nucleotide and predicted amino acid sequence identity are evident when the segmental elements that constitute the immunoglobulin gene loci in phylogenetically divergent vertebrates are compared. However, the organization of gene loci and the manner in which the independent elements recombine (and diversify) vary markedly among different taxa. One striking pattern of gene organization is the "cluster type" that appears to be restricted to the chondrichthyes (cartilaginous fishes) and limits segmental rearrangement to closely linked elements. This type of gene organization is associated with both heavy- and light-chain gene loci. In some cases, the clusters are "joined" or "partially joined" in the germ line, in effect predetermining or partially predetermining, respectively, the encoded specificities (the assumption being that these are expressed) of the individual loci. By relating the sequences of transcribed gene products to their respective germ-line genes, it is evident that, in some cases, joined-type genes are expressed. This raises a question about the existence and/or nature of allelic exclusion in these species. The extensive variation in gene organization found throughout the vertebrate species may relate directly to the role of intersegmental (V<==>D<==>J) distances in the commitment of the individual antibody-producing cell to a particular genetic specificity. Thus, the evolution of this locus, perhaps more so than that of others, may reflect the interrelationships between genetic organization and function.      

Antilipolytic activity in vitro of various analogs of nicotinic acid. Structure-activity relationship

The antilipolytic activity of a series of N aryl-nicotinamides and of alpha picolinic acid, has been tested in vitro. Lipolysis was stimulated by epinephrine (20 micrograms/ml of incubation medium) using rat's epididymal adipose tissue slices. Only N(2-carboxy methyl phenyl) nicotinamide showed antilipolytic effect comparable to that of nicotinic acid at similar concentrations (2 X 10(-5) M). Picolinic acid (10(-4) M) showed no antilipolytic effect. These results, together with those of the literature, are discussed in regard to the relations between structure and antilipolytic activity.