Assessing Interactions between Helical Aromatic Oligoamide Foldamers and Protein Surfaces: A Tethering Approach.

Helically folded aromatic foldamers may constitute suitable candidates for the ab initio design of ligands for protein surfaces. As preliminary steps toward the exploration of this hypothesis, a tethering approach was developed to detect interactions between a protein and a foldamer by confining the former at the surface of the latter. Cysteine mutants of two therapeutically relevant enzymes, CypA and IL4, were produced.

Structure of a complex formed by a protein and a helical aromatic oligoamide foldamer at 2.1 Å resolution.

In the search of molecules that could recognize sizeable areas of protein surfaces, a series of ten helical aromatic oligoamide foldamers was synthesized on solid phase. The foldamers comprise three to five monomers carrying various proteinogenic side chains, and exist as racemic mixtures of interconverting right-handed and left-handed helices. Functionalization of the foldamers by a nanomolar ligand of human carbonic anhydrase II (HCA) ensured that they would be held in close proximity to the protein surface.

Comparison of ultradian and circadian oscillations of carbon dioxide production by various endotherms.

Carbon dioxide emission (VCO2) was computed every 20 min from continuous CO2 concentration recordings taken during 3-30 consecutive days, in strictly controlled environmental conditions, in 54 OF1 mice, 99 Japanese quail, 66 Sprague-Dawley rats, 50 Hartley guinea pigs, 7 chicks, for 7-15 days on 2 Cynomolgus monkeys, and for 24 h on 7 premature infants. This VCO2 shows circadian and ultradian oscillations that were analyzed for frequencies and amplitudes in light-dark 12-h alternation (LD 12:12), continuous light (LL), and continuous dark (DD). Circadians were not always identified or were often masked in LL or DD (mostly in guinea pigs, quail, and rats), while ultradians (tau > or = 40 min) were found in all species, at every time, and in all light regimens.

Rats grouping and the circadian and ultradian synchronization of their carbon dioxide emission by a light-dark 12:12 h alternation.

Carbon dioxide emission (VCO2) was continuously recorded during 19 consecutive days in 25 Sprague Dawley young male rats placed in the same "respiratory chamber", grouped by 5 (G) and then separated (S). All rats were in controlled environmental conditions (20 degrees C temperature, humidity, ventilation, food and water ad libitum) and submitted to a light (100 lux)-dark alternation (LD 12:12). The curves obtained with the respiratory chamber CO2 concentration sampled every 20 minutes were analyzed for circadian periods, amplitudes, phases, ultradian peak oscillation intervals and amplitudes, and VCO2 time variations at L-->D and D-->L light transitions.

The occurrence and functions of ultradian rhythms.

Ultradian oscillations with periods between 5 min and 4 h have been described in cell-free extracts, single-celled eukaryotes, cultured cells and embryos. Whereas some of these potentially oscillatory systems (e.g.

Ultradian and circadian compartmentalization of respiratory and metabolic exchanges in small laboratory vertebrates.

Carbon dioxide emission (VCO2) taken as an index of respiratory and metabolic exchanges, was continuously recorded during 4-30 consecutive days in 100 quail, 87 chicks, 347 rats, 665 mice and 70 guinea-pigs which were under controlled environmental parameters. Harmonic analysis, fast Fourier transform, chi-square periodograms, peak and trough intervals were computed with VCO2 values obtained with CO2 concentrations sampled every 20 min on the CO2 recordings. In LD 12:12 alternation, circadian rhythms were observed in all quail, chicks, rats and mice, but only in 80% of the guinea-pigs.

Respiratory and metabolic ultradian (40 min

Oxygen consumption (VO2) and carbon dioxide emission (VCO2) have been continuously recorded for 24 consecutive hours in 7 premature infants with a range of gestational age of 29-31 weeks at birth, and placed in incubators within a thermal neutral limit. These infants, submitted to continuous light, were fed every 3-4h through a gastric tube which was left in their stomachs throughout the whole experiment. Variance and spectral analyses performed on VCO2 values sampled on the recordings every 10 min showed ultradian variations, in the 40 min-6 h period range, which represent 20 and even 40% of the mean level.

Ultradian, circahoral and circadian structures in endothermic vertebrates and humans.

1. For more than 30 years many studies have been carried out concerning rhythms with periods approaching 24 hr (circadian rhythms). 2.

Societal synchronization in groups of rats or quail submitted to various lighting regimens.

Groups of rats or of quail that had been previously synchronized in a light (L = 100 lux) dark (D) phase opposition (PO = LD and DL) were placed together in a L12:D12 or D12:L12 alternation or in continuous light (LL) or continuous darkness (DD). Emission of carbon dioxide (VCO2) which was continuously recorded in groups of individuals placed in respiratory chambers under controlled environmental conditions allows an index of their overall respiratory and metabolic exchanges to be found. In PO animals placed in LD or DL, the VCO2 circadian light dark synchronization comes back less quickly in rats than in quail, and the VCO2 variations at the light dark transitions (L-D and D-L) remain unchanged in rats, but are modified in quail.

Ultradian and circadian CO2 emission variations in nocturnal and diurnal animals exposed to a light stimulus.

1. Carbon dioxide emission (VCO2) has been continuously recorded in three laboratory animal species (Sprague-Dawley rats, Japanese quail, Hartley guinea-pigs) which differ by their nocturnal and diurnal activities. A 100 lux stimulus has been delivered at various time intervals.

Night-to-night variability of sleep respiratory pauses in normal infants.

Pneumograms have been recorded for several (6-14) consecutive nights in 11 normal children aged 1-257 days. They enabled to assess greater or equal to 5 seconds respiratory pauses. No statistical differences were found between the number of respiratory pauses per hour recorded during subsequent nights on each subject.

Periodic analysis of ultradian (40 min less than tau less than 24h) respiratory variations in laboratory vertebrates of various circadian activities.

Continuous recordings of respiratory gas exchanges of various laboratory endotherm vertebrate species, which have either a nocturnal (mouse, rat) or diurnal (monkey, quail, chicken) or equivocal (guinea-pig) maximal activity, kept under controlled environmental conditions of temperature, humidity, ventilation and provided with food and water ad libitum, show ultradian oscillations of mean and low frequencies (1 less than f less than 35 c.day-1). Harmonic analysis was used to assess periodic or random ultradian variations and to compute amplitudes and phases of these oscillations when these vertebrates were submitted to a light (100 lx) and dark circadian alteration (LD 12:12).

Age and survival of an acute carbon monoxide intoxication: an animal model.

Pathogen-free OF1 male and female mice of six different ages (between 31 and 387 days), grouped by 10, sex-separated and synchronized by a light (100 lux)-dark 12:12 alternation, were submitted to an acute LD50 carbon monoxide intoxication during the light period during which respiratory and motor activities are at a minimum. For this range of ages carbon monoxide survival is not significantly influenced by age and is significantly (P less than 0.001) less so in males than in females.

Effects of aging on circadian and ultradian respiratory rhythms of rats synchronized by an LD12:12 lighting (L = 100 lx).

Continuous monitoring of emitted carbon dioxide (VCO2) was taken as an index of respiratory exchanges in male Sprague-Dawley rats of different ages (31-814 days) submitted to a light (100 lx)-dark (LD) 06.00-18.00 h alternation at a temperature of 20 degrees C and with food and water ad libitum.

Starvation and respiratory rhythmic behavior in groups of light-dark synchronized Sprague-Dawley rats.

Twenty adult male SPF Sprague-Dawley rats, grouped by 5 and synchronized by a light (L)-dark (D) 12:12 alternation, were deprived of food and water for 7 days; 20 other rats were taken as controls. Continuous measurement of emitted carbon dioxide (VCO2), which was taken as an index of respiratory and metabolic exchanges, shows that starvation significantly (p less than 0.001) decreases the amplitudes of the circadian VCO2 rhythms (by 42.

[Respiratory ultradian variations of mean and low frequencies (from 2-80 cycles per day) in premature human infants].

Oxygen consumption (VO2) and carbon dioxide production (VCO2) were continuously measured in premature human (mean gestation age of 31 weeks at birth), nursed in incubators within a neutral thermal environment and submitted to a continuous lighting. At a mean postnatal age of 30 days, and for a mean body weight of 1.8 kg, spectral analysis shows VO2 and VCO2 ultradian variations of mean and low frequencies (2 less than f less than 80 c.

Biological parameters in Japanese quail genetically selected for resistance or sensitivity to an acute hypoxic survival.

Various biological parameters were measured in two strains of Japanese quail selected for their resistance (Ls+) or susceptibility (Ls-) to an acute normobaric hypoxic challenge. Adults of these two strains showed very little or no significant differences concerning body weights, carbon dioxide emission, photoperiodic (L----D and D----L) respiratory reactions, cloacal temperatures, heart rates and ECG QRSII amplitudes, red blood cell data, hemoglobin electrophoresis, and plasma corticosterone (before and after an hypoxic challenge). Enzymatic capacities of phosphofructo-and pyruvate kinases, of glucose-6-phosphatase, lactico- and malate-dehydrogenases, measured in brains and hearts, showed but few statistically significant differences.

Sex-related factors in acute carbon monoxide intoxication in one strain of mice.

In the OF1 mouse strain, males are less resistant than females to acute carbon monoxide intoxication. Castration of males increases their resistance to carbon monoxide. For Neonates injected with four different doses of testosterone (20-500 mg per kg) or oestradiol (2-50 mg per kg), more effect on resistance to carbon monoxide in the (adult) mice was found for oestradiol than for testosterone.

Ultradian and circadian respiratory rhythms in grouped small laboratory vertebrate species as a method to assess the effects of environmental challenges.

The recording over several days of the respiratory gases of groups of different laboratory vertebrates (mice, rats, quails), placed in a chamber with controlled ventilation, and in standardized environmental conditions of temperature, humidity, light, noise and feeding, shows ultradian (tau less than 24 hr) and circadian (tau congruent to 24 hr) rhythms. A simple variance analysis method shows periodic carbon dioxide changes, due to different environmental stimuli. Societal, light, acoustical, carbon monoxide and starvation challenges are given as examples.

Respiratory behavior in groups of deaf and non-deaf GFF male mice.

Carbon dioxide emission (VCO2) of groups of 10 GFF mice, genetically deaf and non-deaf, were compared, in controlled conditions of temperature 20-21 degrees C, humidity 50-80% and light (LD12:12; L = 108 lux). A circadian rhythm of VCO2 was evidenced in both genotypes, with levels in D and in L significantly (0.001 less than p less than 0.

Sex-related factors in acute hypoxia survival in one strain of mice.

In mice of different ages from the OF1 mouse strain, males are less resistant than females to a normobaric hypoxia obtained in a few hours by a progressive lowering of normoxic PO2 with nitrogen flushing. Injection of estradiol to castrated males and spayed females increases hypoxic survival. Neonates which have been injected with a high dose of estradiol show, when adult, a high hypoxic resistance.

Effects of B16 melanoma transplantation on the respiration of grouped C57Bl female mice.

Two batches of 110 females C57Bl mice were grafted with B 16 melanoma, the first batch at the age of 67 days, the second at 82 days. The animals were divided into groups of 10, and kept under a LD 12 : 12 regimen. The growth of the tumors was more rapid in the second batch.

Lead, cadmium, iron, zinc, copper, manganese, calcium and magnesium in SPF male rats exposed to a dilution of automotive exhaust gas throughout their lives.

Male pathogen free CFE albino Sprague Dawley rats were exposed 8 h per day, 5 days per week, for three years to a 1/1000 dilution of automotive exhaust gas, containing 58 ppm carbon monoxide, 0.37% carbon dioxide, 23 ppm nitrogen oxides, 2 ppm aldehydes, less than 5 mg/l hydrocarbons and 8.5 micrograms/m3 lead.