Kinetics of the activation of rat liver pyruvate kinase by fructose 1,6-disphosphate and methods for characterizing hysteretic transitions

1. Kinetics of fructose 1,6-diphosphate activation of liver pyruvate kinase type I inhibited with MgATP and l-alanine are described as a function of enzyme and fructose 1,6-diphosphate concentrations. These results can be explained by a single pseudo-first-order transition of the enzyme into an active form, independent of the enzyme concentration. This rate constant, k(app.)=0.24s(-1) with 0.02mm-fructose 1,6-diphosphate (t(0.9) approximately 10s where t(0.9) is the time for 90% conversion), is an increasing function of fructose 1,6-diphosphate concentration far beyond that needed to maximally activate enzyme equilibrated with fructose 1,6-diphosphate (about 20mum). 2. The model equations are best analysed with numerical techniques which are described. These techniques are useful in studying similar slow transients frequently observed in stopped-flow studies of enzymes. 3. Shorter transients (t(0.9)=0.5-1.5s) were observed in the kinetic response of the enzyme to the addition of MgATP or phosphoenolpyruvate, but were not further characterized.     

Learned specification of concept neurons

The referential aspect of a concept can be defined by a disjunction of conjunations of attributes. A single neuron can represent a disjunction of conjunctions of attributes if the assumption that neurons are single-threshold devices is discarded. Instead, one must assume that such concept neurons are composed of hundreds or thousands of (high-threshold) receptive areas, each containing tens or hundreds of synaptic sites. When essentially all of the sites of a receptive area are activated in close temporal contiguity, the receptive area generates a local (spike) response which is assumed to be sufficient to fire the cell body and axon of the neuron. If we assume that all concepts possessed by a single human being can be encoded by single neurons in this manner, there are enough neurons in the human cortex only if we assume that most of these concept neurons are specified by learning. Genetic specification is ruled out by the enormous (infinite?) nember of possible concepts humans appear to be able to learn. Therefore, a speculative neural mechanism is presented regarding how “free” neurons could become specified by learning.     

A Tranquilizer-Anticholinergic Preparation in Functional Gastrointestinal Disorders: A Double-Blind Evaluation

Chlordiazepoxide plus clidinium bromide (Librax®) was evaluated and compared with a placebo by means of a random sample, double-blind crossover technique in 42 patients presenting ordinary functional gastrointestinal disorders.Results:• 73.9 percent excellent-to-good response to the active drug in patients receiving it before they received the placebo, compared with 44.5 percent in those who did not receive it until after the placebo period.• 58.9 percent excellent-to-good response to the active drug in patients who received it after the placebo period, as compared with 31.8 percent in those receiving the placebo last.• Overall clinical response 67.5 percent excellent-to-good with the active drug as compared with 37.5 percent with the placebo.• Excellent-to-good results in 12 follow-up patients receiving the known active drug.• Statistically significant symptomatic response in four of eight target symptoms.The tranquilizer-anticholinergic preparation used appeared to improve not only patient outlook and attitudes but to effectively relieve both the physiologic and psychic manifestations of common functional gastrointestinal disorders.     

Distribution of Neuraminidase among Food-poisoning Strains of Clostridium perfringens

A survey was made to determine the distribution of the enzyme neuraminidase among 76 strains of Clostridium perfringens. Representative strains from each toxigenic type (A to F) and atypical C. perfringens type A food-poisoning strains of both American and English (Hobbs types) origin were tested. Both the American food-poisoning and nonfood-poisoning associated cultures consisted of both neuraminidase-positive and -negative strains. Furthermore, American strains which could not be differentiated from the original Hobbs cultures consisted of both neuraminidase-positive and -negative representatives. In contrast, the English (Hobbs) strains uniformly failed to produce an active intracellular or extracellular neuraminidase. No enzyme activity was detected in these strains when cultures were grown in different growth media, when grown in the presence of substrate (neuraminlactose), or upon extended incubation of enzyme preparations with substrate. With the exception of a type F strain, representative strains of the other toxigenic types (A to F) produced neuraminidase; 85% of the typical type A strains contained the enzyme.     

Effects of photoperiod and social variables on reproduction and growth in the male musk shrew (Suncus murinus)

In Exp. 1, the time course for the photoperiodic response in juvenile male musk shrews was examined by exposing animals to short (10L:14D) or long (14L:10D or 18L:6D) daylengths for 10, 20, 40 or 56 days. When compared with the response of animals maintained in long days, those exposed to short days showed an inhibition of reproductive maturation by 40 days of treatment. In Exp. 2, the combined effects of photoperiod and social cues were investigated in juvenile males that were either housed in short days (with or without a female) or in long days (with or without a female) for 40 days. The short photoperiod was generally inhibitory to sexual maturation, while the presence of an adult female was generally stimulatory, i.e. animals living with a female in long days had the greatest level of sexual maturity, while those living alone in short days had the lowest level of maturity. Animals that received opposing signals, i.e. short days in the presence of a female, had an intermediate response which was equivalent to the response seen in males living alone in long days. These results suggest that the presence of a female can partly reverse inhibitory effects of short days. In Exp. 3, the effects of photoperiod and social cues on the reproductive physiology of the adult male (same design as in Exp. 2) were investigated. The results show that the adult male musk shrew is responsive to both photoperiodic and social cues, in a manner similar to that of juvenile animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vectors permitting visual monitoring of simple transposition events

The construction and use of two novel transposon(Tn)-delivery vectors is described. These vectors carry Inc.W or Inc.N broad-host-range transfer functions cloned next to the narrow-host-range replicon of pBR329. The host specificities of pSLX10 and pSLX23 both complement and extend the host specificities of existing Tn delivery vectors. Plasmids pSLX10 and pSLX23 were shown to transfer at high frequency in intergeneric matings. The lux genes which are present on each vector permit the visual monitoring of transconjugants which have retained a Tn element, but are devoid of plasmid molecules. pSLX10 and pLSX23 were efficiently used to generate a range of auxotrophic mutants in various strains of Pseudomonas as well as to clone genes from Serratia liquefaciens. These vectors may have general applicability to identify and clone genes in a wide range of Gram-negative bacteria.     

Genetic and morphological divergence among sympatric canids

Numerous studies have suggested that the extent of character divergence observed between two sympatric species reflects the intensity of competition for resources or space. However, the influence of time on divergence is often overlooked. We examined the relationship between time and character divergence in two groups of congeneric, sympatric canids on two continents: South American foxes and African jackals. Character divergence was assessed from measurements of body mass and dental and cranial shape. Divergence time was estimated from data on mitochondrial DNA restriction site polymorphisms. Our findings indicate that African jackals are morphologically similar despite having diverged more than 2 million years ago. By contrast, South American foxes differ substantially in both size and morphology after only 250,000 years of evolution. Thus, the lack of character divergence among the African jackals cannot be explained as a result of very recent common ancestry.     

Class I major histocompatibility complex cDNA clones from sheep thymus: alternative splicing could make a long cytoplasmic tail

To investigate the class I major histocompatibility complex (MHC) genes expressed in the young sheep thymus, a cDNA library was screened with a human HLA-B7 cDNA probe under conditions of relaxed stringency. Thirteen clones were isolated and found by partial sequences to fall into five classes, requiring the expression of at least three loci. One sequence was found six times, almost half of the total, and may thus represent the major message expressed in the young sheep thymus. One of the clones was found to have failed to excise the intron between cytoplasmic exons 7 and 8, leading to the predicted synthesis of a cytoplasmic domain 23 amino acids longer than the other sheep sequences, and 15 amino acids longer than any cytoplasmic domain previously described. The sequences of all the clones were found to be most similar to bovine, and least similar to mouse class I MHC sequences.The nucleotide sequence data reported in this paper have been sunmitted to the GenBank nucleotide sequence database and have been assigned the accession numbers M 34672-6.