Reproduction numbers and thresholds in stochastic epidemic models. I. Homogeneous populations.

We compare threshold results for the deterministic and stochastic versions of the homogeneous SI model with recruitment, death due to the disease, a background death rate, and transmission rate beta cXY/N. If an infective is introduced into a population of susceptibles, the basic reproduction number, R0, plays a fundamental role for both, though the threshold results differ somewhat. For the deterministic model, no epidemic can occur if R0 less than or equal to 1 and an epidemic occurs if R0 greater than 1. For the stochastic model we find that on average, no epidemic will occur if R0 less than or equal to 1. If R0 greater than 1, there is a finite probability, but less than 1, that an epidemic will develop and eventuate in an endemic quasi-equilibrium. However, there is also a finite probability of extinction of the infection, and the probability of extinction decreases as R0 increases above 1.     

Pseudohyperkalaemia.

When the serum potassium concentration is raised and there is no clinical or electrocardiographic evidence of hyperkalaemia pseudohyperkalaemia must be considered.     

Mammalian glycosyltransferases: genomic organization and protein structure.

In recent years, several glycosyltransferase genes and cDNAs have been cloned and characterized. Although the glycosyltransferases seem to share the same general architecture, there is only little sequence similarity between the various enzymes. Moreover, a comparison of the organization of the genes shows that there is no common pattern of intron-exon structure. In addition, there seems to be little or no correlation between glycosyltransferase exons and protein domains. Taken together, these observations suggest that many of the glycosyltransferase genes evolved independently. So far, only two glycosyltransferase gene families have been described. These families may have evolved by exon-shuffling, or by gene duplication and subsequent divergence. For specific glycosyltransferases, mechanisms such as alternative splicing and alternative promoter usage play a role in the production of multiple protein isoforms from a single gene. These isoenzymes may differ in their enzymatic properties or cellular localization.     

The Evolutionary Advantage of Recombination. II. Individual Selection for Recombination

Based on the Fisher-Muller theory of the evolution of recombination, an argument can be constructed predicting that a recessive allele favoring recombination will be favored, if there are either favorable or deleterious mutants occurring at other loci. In this case there is no clear distinction between individual and group selection. Computer simulation of populations segregating for recessive or dominant recombination alleles showed selection favoring recombination, except in the case of a dominant recombination allele with deleterious background mutants. The relationship of this work to parallel investigations by Williams and by Strobeck, Maynard Smith, and Charlesworth is explored. All seem to rely on the same phenomenon. There seems no reason to assume that the evolution of recombination must have occurred by group selection.     

Aging in the lumbar spine. II. L1 and L2

The bodies of the first and second lumbar vertebrae, like those of L3 and L4, show a significant trend toward lowering and broadening with age. Superior, inferior, and midbody transverse breadths increase, but there is little or no increase in endplate "flaring" with age. There is essentially no change in the relationship between anterior and posterior heights, but as reported for L3 and L4, there is a sexual difference in the amount and type of wedging of the bodies of L1 and L2. Posterior wedging (posterior height less than anterior height) of these vertebrae is about twice as common in females as in males. Whites of both sexes show a statistically significant relationship between age and increased biconcavity of the endplates. Black females, but not the males, show a similar trend, especially in L1.     

Immunochemical studies on lactate dehydrogenase A subunit deficiencies.

In lactate dehydrogenase (LDH) A subunit deficiency, is there not only a lack of activity but also a lack of subunit production? We demonstrated three remarkable points to answer this question: There are no proteins that immunologically react with anti-A subunits. There are no heterotetramers that react with anti-B subunits. B subunits seem to be genetically produced at normal level, and all of them form only one isoenzyme, LDH-B4. From these points, we concluded that there is a complete lack of A subunit production or production of incomplete A subunits that can neither react with anti-A subunits nor form heterotetramers.     

A convenient method for the ATPase assay.

A new method for the determination of inorganic phosphorus released in ATPase assay has been evaluated. The method is based on the reduction of a phosphomolybdate complex by Elon in a copper acetate buffer. In contrast to current methods, there is no interference by ATP with color development. There is also less or no interference by other compounds usually present in ATPase assay media. The method is simple, sensitive, and reproducible.     

Glycogen synthesis by hepatocytes from diabetic rats.

Hepatocytes prepared from streptozotocin- and alloxan-diabetic rats starved for 24 h contain 0.5--2% wet wt. of glycogen. Glycogen synthesis in the hepatocytes from such rats, after prior depletion of the glycogen by glucagon injection, was studied. As distinct from cells from normal animals, there was no glycogen synthesis from glucose as sole substrate, even at concentrations of 60 mM. When supplied with glucose, a gluconeogenic precursor (lactate, dihydroxyacetone or fructose), and with glutamine there was concurrent synthesis of glucose and of glycogen. Without glutamine there was little or no glycogen synthesis. The rate of glycogen formation was in the same range as for cells from control rats. Glutamine addition markedly activated glycogen synthase in cells of starved diabetic rats, but there was no effect on phosphorylase. We obtained very little synthesis of glycogen with hepatocytes from fed diabetic rats, whereas with normal animals, synthesis by such cells equals or exceeds that obtained from starved rats. The conversion of synthase b (inactive) into the active form was studied in rat liver homogenates. The activation of the synthase in cells from starved diabetic rats is somewhat less than that from normal animals, but that from fed diabetic rats is markedly decreased compared with that in livers of fed control animals or that of starved diabetic animals.     

Metabolism of dog gastric mucosa. Nucleotide levels in parietal cells.

Adenine and pyridine nucleotide levels as well as those of phosphate, phosphocreatine, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, glucose, and glycogen were measured in histologically defined parietal and mucous cell sections of biopsies of dog gastric mucosa at rest, and in various secretory states. As a result of stimulation of secretion, there appeared to be no change in adenine nucleotide levels, or phosphocreatine, but there was a rise in inorganic phosphate and a fall in phosphorylation potential. However, there was a marked increase in NADH, but no change in NADPH with onset of acid secretion. The increase in the lactate to pyruvate ratio showed that the increased NADH level occurred in the cytoplasm and these data are discussed with reference to change in cell pH.     

Hereditary multiple exostosis. A comparative genetic evaluation in man and horses.

Comparative studies are being conducted on hereditary multiple exostosis in man and the horse. In both, there is an unquestionable inheritance pattern of a typical single, dominant, autosomal gene. Those who carry the gene have a one-half chance of transmitting it to each offspring, whereas, those who do not carry the gene do not transmit this abnormality to their progeny. The lesions are clinically and histologically similar; no persistent chromosomal irregularities have been associated with the abnormality in either man or the horse and no single evidence of malignancy in either man or animal has been detected in this study to date.     

Photochemistry of monomethylated and permethylated bacteriorhodopsin.

Methylation of the nonactive site lysines of bacteriorhodopsin to form permethylated bacteriorhodopsin does not interfere with the formation of the short wavelength intermediate M412 or light-induced proton release/uptake. The absorption spectrum is similar to that of the native bacteriorhodopsin. However, additional monomethylation of the active site lysine of bacteriorhodopsin causes a red shift of the absorption maximum from 568 nm in light-adapted bacteriorhodopsin [BR] to 630 nm. The photochemistry of active-site methylated BR does not proceed beyond the L-photointermediate. In particular, the photointermediate corresponding to M412 does not form, and there is no proton pumping. Moreover, there is no tyrosine deprotonation. Thus, the formation of an M-type photointermediate is required for proton pumping by BR.     

Value of x ray examinations of the cervical spine.

The value of x ray examination of the cervical spine was studied. In one district general hospital it has been estimated that such examinations occupy one radiographer and one room for four hours a week. Eighty-five per cent of patients aged 60 or more who had been referred for an x ray examination of the neck in one year were reported as having cervical spondylosis, and there were no unexpected findings of infection or malignancy at any age. The reports of patients referred for x ray examination of the cervical spine were compared with those of control patients who had originally attended for barium studies. There was no significant difference in the prevalence of cervical spondylosis between the two groups, although the severity of the disc changes was greater among cases than controls. There were no consistent relations between symptoms and changes seen on x ray films. It is suggested that x ray examinations should be performed only when there is a clinical suspicion of malignancy or infection, after trauma, or when surgery may be indicated. There is little point in taking x ray films of the neck to diagnose cervical spondylosis.     

Computer-aided material balancing for prediction of fermentation parameters.

Despite the importance of biomass as a parameter in fermentation processes, there are no commercially available sensors suitable for its measurement. An indirect approach for the assessment of biomass concentration can be based on material balances and on the direct monitoring of fermentation parameters for which there are established sensors (e.g., gaseous oxygen and carbon dioxide). As a consequence, this method requires no assumption of cellular yield coefficients or rate constants. This approach is also readily adaptable to general use since it requires only some knowledge of the compositions of the substrate, cells, and noncellular products.     

Hydrolases in intracellular compartments of rat liver cells. Evidence for selective activation and/or delivery.

We used perfused rat livers to investigate the role of endosomes versus lysosomes in the hydrolysis of endocytosed material. When perfusions were performed at 37 degrees C with 125I-asialoorosomucoid, 125I-galactosylated albumin, or 125I-mannosylated albumin, there was a 15-min lag before trichloroacetic acid-soluble degradation products were detected. Furthermore, no hydrolysis was detected at 16 degrees C, indicating that there was no significant prelysosomal degradation of these proteins. Since detection by this method depends on extensive hydrolysis, we subsequently used three small synthetic molecules from which fluorescent products are generated by a single cleavage. These were 4-methylumbelliferyl sulfate, 4-methylumbelliferyl phosphate, and 4-methylumbelliferyl-beta-D-glucosaminide, which are substrates for aryl sulfatase, acid phosphatase, and beta-hexosaminidase, respectively. Using the first two compounds, hydrolysis was detected after 3 min at 37 degrees C and still occurred, albeit to a reduced extent, at 16 and 4 degrees C. This indicates that aryl sulfatase and acid phosphatase are active prelysosomally. We found a different result with 4-methylumbelliferyl-beta-D-glucosaminide. At 37 degrees C, there was a greater than 15-min lag before hydrolysis products were measured; furthermore, hydrolysis ceased at 16 degrees C, indicating that beta-hexosaminidase is active lysosomally. Taken together, these findings show that there is selective activation and/or delivery of hydrolases along the endocytic pathway.     

Mastalgia and total body water.

Total body water (TBW) was measured early and late in a menstrual cycle in 56 women, 39 of whom had breast pain. The remainder were asymphtomatic controls. Most women did not conform to the traditional view that there is a premenstrual increase in TBW. In some TBW decreased, while in others there was no change from the early cycle measurement. No TBW pattern correlated with any syndromes of breast pain or with any psychoneurotic profile.     

Quantitative analysis of muscle cell changes in compensatory hypertrophy and work-induced hypertrophy.

The cytological characteristics of two modes of muscle hypertrophy were studied in the extensor digitorum longus muscle of the rat. Comprensatory hypertrophy (CH) was produced by tenotomy of the tibialis anterior muscle and work-induced hypertrophy (WIH) was produced by forced swimming of the animal. While both methods produced an increase in muscle weight and cell size, these two parameters did not correlate. Morphometric analyses of the hypertrophied muscle cells demonstrated that in CH-muscle there was an increase in mitochondrial volume density, a decrease in myofibrillar volume density and no change in sarcotubular or nuclear volume density. WIH-muscle demonstrated an increase in sarcotubular volume density but no change in mitochondrial, myofibrillar or nuclear volume density. It is concluded that in CH-muscle, the cell volume increase is attributable to mitochondrial volume increase and that there is no increase in the contratile myofibrillar component of the cell. WIH-muscle, on the other hand, has a cell volume increase which is attributable to a proportional increase in these organelles.     

Costly signaling and cooperation.

We propose an explanation of cooperation among unrelated members of a social group in which cooperation evolves because it constitutes an honest signal of the member's quality as a mate, coalition partner or competitor, and therefore results in advantageous alliances for those signaling in this manner. Our model is framed as a multi-player public goods game that involves no repeated or assortative interactions, so that non-cooperation would be a dominant strategy if there were no signaling benefits. We show that honest signaling of underlying quality by providing a public good to group members can be evolutionarily stable, and can proliferate in a population in which it is initially rare, provided that certain plausible conditions hold, including a link between group-beneficial signaling and underlying qualities of the signaler that would be of benefit to a potential mate or alliance partner. Our model applies to a range of cooperative interactions, including unconditionally sharing individually consumable resources, participating in group raiding or defense, and punishing free-riding or other violations of social norms.     

Phosphocreatine does not inhibit rabbit muscle phosphofructokinase or pyruvate kinase.

Certain phosphocreatine preparations contain a contaminant that inhibits phosphofructokinase and pyruvate kinase assays. The contaminant can be separated from phosphocreatine by anion exchange chromatography. After appropriate purification, phosphocreatine has no effect on phosphofructokinase or pyruvate kinase; thus, there is no evidence that it serves muscle as a regulator of these enzymes. Although the inhibitory preparations of phosphocreatine contain inorganic phosphate and trace amounts of more negatively charged phosphorylated contaminants, the inhibitor is not inorganic phosphate or pyrophosphate. The nature of the inhibitor remains to be determined.     

Preliminary X-ray crystallographic data on phospholipase C from Bacillus cereus.

Low-angle X-ray diffraction shows that, despite the well-defined regular axially projected structure, there is no long-range lateral order in the packing of molecules in native (undried) or dried elastoidin spicules from the fin rays of the spurhound Squalus acanthias. The equatorial intensity distribution of the X-ray diffraction pattern from native elastoidin indicates a molecular diameter of 1.1 nm and a packing fraction for the structure projected on to a plane perpendicular to the spicule (fibril) axis of 0.31 (the value for tendon is much higher at around 0.6). Density measurements support this interpretation. When the spicule dries the packing fraction increases to 0.43 but there is still no long-range order in the structure. The X-ray diffraction patterns provide no convincing evidence for any microfibrils or subfibrils in elastoidin. Gel electrophoresis shows that the three chains in the elastoidin molecule are identical. The low packing fraction for collagen molecules in elastoidin explains the difference in appearance between electron micrographs of negatively stained elastoidin and tendon collagen. In elastoidin, but not in tendon collagen, an appreciable proportion of the stain is able to penetrate between the collagen molecules.     

Proteomics for Biological Discovery * Edited by T.D. Veenstra and John R. Yates

An understanding of the roles and interactions of proteins withincells is vital to our understanding of biology. Proteomics hascome a long way, and covers many areas now, since the inventionof 2 dimensional gel electrophoresis in the 1970s, or the coiningof the term proteomics in the 1990s. As more people move intothis important area, there is a need for guides to aid thesemoves. Proteomics for Biological Discovery aims to serve assuch a guide. The format of this multi-author book is well laidout, with fifteen chapters in three main parts: I. Foundationsof Proteomics; II. Functional Proteomics; and III. Novel Approachesin Proteomics. The editors have selected a strong team of respectedexperts in the various proteomics niches to write the fifteenconstituent chapters. The chapters are, for the most part, self-contained,and there is no