The derivation of certain pandemic bounds

Exact results have previously been obtained concerning the spread of infection in continuous space contact models describing a class of multitype epidemics. The Pandemic Theorem gave a lower bound for the spatial final size. A discrete space model is considered. A simpler, more direct proof based on an infinite matrix formulation of the final size equations is used to obtain the pandemic result for this model. An upper bound is obtained, which is valid for both continuous and discrete space models. This enables a limiting result to be obtained for the spatial final size when the amount of initial infection tends to zero.     

Strategic and genetic models of evolution

A new model which allows both for the effect of behavioural patterns on productive matings and for parental investment in the survival of offspring to maturity is considered. This combines ideas from genetics and evolutionary game theory, and provides a more realistic formulation to describe mating behaviour than the traditional 'battle of the sexes' model. Allowing individuals to migrate leads to spatial versions of both models. The saddle point method is used to obtain the speed of first spread of new genes/strategies in both spatial systems.     

Glycosylation of serum ribonuclease 1 indicates a major endothelial origin and reveals an increase in core fucosylation in pancreatic cancer

Human pancreatic ribonuclease 1 (RNase 1) is a glycoprotein expressed mainly by the pancreas and also found in endothelial cells. The diagnosis of pancreatic cancer (PaC) remains difficult and therefore the search for sensitive and specific markers is required. Previous studies showed that RNase 1 from human healthy pancreas contained only neutral glycans, whereas RNase 1 from PaC cell lines contained sialylated structures. To determine whether these glycan tumor cell-associated changes were also characteristic of serum RNase 1 and could be used as a marker of PaC, we have analyzed the glycosylation of serum RNase 1. The origin of serum RNase 1 was also investigated. Serum RNase 1 from two PaC patients and two controls was purified and the glycans analyzed by high-performance liquid chromatography (HPLC)-based sequencing and mass spectrometry. Although normal and tumor serum RNase 1 contained the same glycan structures, there was an increase of 40% in core fucosylation in the main sialylated biantennary glycans in the PaC serum RNase 1. This change in proportion would be indicative of a subset of tumor-associated glycoforms of RNase 1, which may provide a biomarker for PaC. Two-dimensional electrophoresis of the RNase 1 from several endothelial cell lines, EA.hy926, human umbilical vein endothelial cells (HUVEC), human mammary microvessel endothelial cells (HuMMEC), and human lung microvessel endothelial cells (HuLEC), showed basically the same pattern and was also very similar to that of serum RNase 1. RNase 1 from EA.hy926 was then purified and presented a glycosylation profile very similar to that from serum RNase 1, suggesting that endothelial cells are the main source of this enzyme.     

The influence of serum,glucose and oxygen on intervertebral disc cell growth <Emphasis Type="Italic">in vitro</Emphasis>: implications for degenerative disc disease

Introduction  

The avascular nature of the human intervertebral disc (IVD) is thought to play a major role in disc pathophysiology by limiting nutrient supply to resident IVD cells. In the human IVD, the central IVD cells at maturity are normally chondrocytic in phenotype. However, abnormal cell phenotypes have been associated with degenerative disc diseases, including cell proliferation and cluster formation, cell death, stellate morphologies, and cell senescence. Therefore, we have examined the relative influence of possible blood-borne factors on the growth characteristics of IVD cells in vitro.     

Identification of Novel Temperature-sensitive Lethal Alleles in Essential β-Tubulin and Nonessential α2-Tubulin Genes as Fission Yeast Polarity Mutants

We have screened for temperature-sensitive (ts) fission yeast mutants with altered polarity (alp1–15). Genetic analysis indicates that alp2 is allelic to atb2 (one of two α-tubulin genes) and alp12 to nda3 (the single β-tubulin gene). atb2⁺ is nonessential, and the ts atb2 mutations we have isolated are dominant as expected. We sequenced two alleles of ts atb2 and one allele of ts nda3. In the ts atb2 mutants, the mutated residues (G246D and C356Y) are found at the longitudinal interface between α/β-heterodimers, whereas in ts nda3 the mutated residue (Y422H) is situated in the domain located on the outer surface of the microtubule. The ts nda3 mutant is highly sensitive to altered gene dosage of atb2⁺; overexpression of atb2⁺ lowers the restrictive temperature, and, conversely, deletion rescues ts. Phenotypic analysis shows that contrary to undergoing mitotic arrest with high viability via the spindle assembly checkpoint as expected, ts nda3 mutants execute cytokinesis and septation and lose viability. Therefore, it appears that the ts nda3 mutant becomes temperature lethal because of irreversible progression through the cell cycle in the absence of activating the spindle assembly checkpoint pathway.     

Participation of plasma membrane proteins in the formation of tight junction by cultured epithelial cells

Measurements of the transepithelial electrical resistance correlated with freeze-fracture observations have been used to study the process of tight junction formation under various experimental conditions in monolayers of the canine kidney epithelial cell line MDCK. Cells derived from previously confluent cultures and plated immediately after trypsin- EDTA dissociation develop a resistance that reaches its maximum value of several hundred ohms-cm(2) after approximately 24 h and falls to a steady-state value of 80-150 ohms- cm(2) by 48 h. The rise in resistance and the development of tight junctions can be completely and reversibly prevented by the addition of 10 μg/ml cycloheximide at the time of plating, but not when this inhibitor is added more than 10 h after planting. Thus tight junction formation consists of separable synthetic and assembly phases. These two phases can also be dissociated and the requirement for protein synthesis after plating eliminated if, following trypsinization, the cells are maintained in spinner culture for 24 h before plating. The requirement for protein synthesis is restored, however, if cells maintained in spinner culture are treated with trypsin before plating. Actinomycin D prevents development of resistance only in monolayers formed from cells derived from sparse rather than confluent cultures, but new mRNA synthesis is not required if cells obtained from sparse cultures are maintained for 24 h in spinner culture before plating. Once a steady-state resistance has been reached, its maintenance does not require either mRNA or protein synthesis; in fact, inhibition of protein synthesis causes a rise in the resistance over a 30-h period. Following treatments that disrupt the junctions in steady- state monolayers recovery of resistance also does not require protein synthesis. These observations suggest that proteins are involved in tight junction formation. Such proteins, which do not turn over rapidly under steady-state conditions, are destroyed by trypsinization and can be resynthesized in the absence of stable cell-cell or cell-substratum contact. Messenger RNA coding for proteins involved in tight junction formation is stable except when cells are sparsely plated, and can also be synthesized without intercellular contacts or cell-substratum attachment.     

Herd-level risk factors associated with the presence of Phage type 21/28 E. coli O157 on Scottish cattle farms

Background  

E. coli O157 is a bacterial pathogen that is shed by cattle and can cause severe disease in humans. Phage type (PT) 21/28 is a subtype of E. coli O157 that is found across Scotland and is associated with particularly severe human morbidity.     

Isolation of plasminogen activator from human plasma by chromatography on lysine-sepharose.

A plasminogen activator has been recovered from human postexercise blood plasma by chromatography on lysine coupled to Sepharose 4B. Plasminogen activator activity was unstable in citrated plasma but could be stabilized by addition of 5 mm EDTA and 5 mm benzamidine. Stabilized postexercise plasma was applied to lysine-Sepharose and the bulk of the protein washed from the column with a gradient in NaCl (0–0.6 m). The activator was then eluted with 1.5 m NaCl or with linear gradients in l-lysine (0–20 mm) or l-arginine (0–0.2 m). The activator was purified approximately 5000-fold over the starting plasma and was well separated from plasminogen and plasmin inhibitors. It caused no lysis on plasminogenfree fibrin-agar plates. The activator activity was inhibited by diisopropylphosphorofluoridate, ?-aminocaproic acid, and lysine but not by soybean trypsin inhibitor, Trasylol or blood plasma with or without heparin present. A plasminogen activator isolated from homogenized human vein by identical chromatography on lysine-Sepharose showed the same inhibition profile. This suggested that the activator recovered from postexercise human plasma was released from the blood vessel walls. Incorporation studies with [³²P]-diisopropylphosphorofluoridate indicated that the enzyme displays over 30,000 Committee on Thrombolytic Agents units/mg of protein. This high potency combined with the activator's resistance to plasma inhibitors suggests that it may be of importance to in vivo fibrinolysis.     

Control of nucleation in the crystallization of lysozyme.

This work investigates the influence of storage of lysozyme in solution on its crystallization. The crystallization of hen egg-white lysozyme exhibits a storage effect (aging) that depends on the length of time the lysozyme solution is stored, after dissolving from freeze-dried powder, before being brought to crystallization conditions. The number of crystals obtained increases, while their size decreases, as the solution ages. Observations suggest that this effect is due to the presence of fungi that multiply in the stored protein solution. This aging effect was used to control nucleation and determine the number and size of lysozyme crystals to be formed in a given sample.     

Accumulation of Ergopeptide Alkaloids in Symbiotic Tall Fescue Grown under Deficits of Soil Water and Nitrogen Fertilizer

The fungus Acremonium coenophialum is endophytically associated with tall fescue (Festuca arundinacea Schreber). Within this symbiotum the fungus produces ergopeptide alkaloids, which are associated with livestock toxicoses. Environmental effects on the production of ergot alkaloids within the symbiotum are unknown. We conducted a greenhouse study of the effects of flooding, nitrogen rate during fertilization (11, 73, and 220 mg of N per pot weekly), nitrogen form (3.4 and 34 mg of N as NH₄⁺ or NO₃^- per pot), and drought stress (-0.03, -0.05, and -0.50 MPa) on ergopeptide alkaloid concentrations in one genotype of nonsymbiotic and symbiotic tall fescue grown in plastic pots. It was determined that the concentration of ergovaline, the major type of ergopeptide alkaloid, was increased but was not as high as that in nonflooded controls. Total ergopeptide and ergovaline concentrations in plants receiving high (220 mg of N per pot) and low (11 mg of N per pot) levels of NH₄NO₃ fertilization were not affected by flooding. The form of nitrogen was important since all concentrations of NO₃^--N increased ergopeptide alkaloid content, as opposed to the effects of NH₄⁺-N, which was effective only at high concentrations (34 mg of N per pot). Ergopeptide concentrations were highest in drought-stressed plants grown at -0.50 MPa and fertilized at the moderate or high N rate. The results suggest that within this genotype, ergopeptide alkaloid biosynthesis by the fungus is not appreciably affected by flooding but is greatly increased by high rates of N fertilization and moderate water deficit.