Diminished Reovirus Capsid Stability Alters Disease Pathogenesis and Littermate Transmission

Reovirus is a nonenveloped mammalian virus that provides a useful model system for studies of viral infections in the young. Following internalization into host cells, the outermost capsid of reovirus virions is removed by endosomal cathepsin proteases. Determinants of capsid disassembly kinetics reside in the viral σ3 protein. However, the contribution of capsid stability to reovirus-induced disease is unknown. In this study, we found that mice inoculated intramuscularly with a serotype 3 reovirus containing σ3-Y354H, a mutation that reduces viral capsid stability, succumbed at a higher rate than those infected with wild-type virus. At early times after inoculation, σ3-Y354H virus reached higher titers than wild-type virus at several sites within the host. Animals inoculated perorally with a serotype 1 reassortant reovirus containing σ3-Y354H developed exaggerated myocarditis accompanied by elaboration of pro-inflammatory cytokines. Surprisingly, unchallenged littermates of mice infected with σ3-Y354H virus displayed higher titers in the intestine, heart, and brain than littermates of mice inoculated with wild-type virus. Together, these findings suggest that diminished capsid stability enhances reovirus replication, dissemination, lethality, and host-to-host spread, establishing a new virulence determinant for nonenveloped viruses.     

Histochemical classification based upon reaction types and its application to carbohydrate histochemistry

Summary A method of classification is presented, which divides histochemical visualization reactions into categories based on general reaction types. This scheme is dependent upon the reaction between two elements, the substrate and the probe. The substrate represents a tissue component(s) with one or more reactive groups that can combine directly with the probe. Alternatively, the substrate reactive groups are chemically modified (activation) with a suitable reagent before reaction with the probe. Probes are of three types: those that yield a coloured product, those that result in a colourless product, and those that produce a coloured product only after a further reaction.Methods used in carbohydrate histochemistry are divided into one, two and three probe reactions. Two probe reactions are further subdivided into sequences involving one or two coloured products (one and two dye sequences); three probe reactions into sequences involving one, two or three coloured products (one, two and three dye sequences). This classification permits the rationalization and organization of methods, and provides a framework for the examination of existing methods and the development of new ones.     

Multiple Phenotypic Changes Associated with Large-Scale Horizontal Gene Transfer

Horizontal gene transfer often leads to phenotypic changes within recipient organisms independent of any immediate evolutionary benefits. While secondary phenotypic effects of horizontal transfer (i.e., changes in growth rates) have been demonstrated and studied across a variety of systems using relatively small plasmids and phage, little is known about the magnitude or number of such costs after the transfer of larger regions. Here we describe numerous phenotypic changes that occur after a large-scale horizontal transfer event (∼1 Mb megaplasmid) within Pseudomonas stutzeri including sensitization to various stresses as well as changes in bacterial behavior. These results highlight the power of horizontal transfer to shift pleiotropic relationships and cellular networks within bacterial genomes. They also provide an important context for how secondary effects of transfer can bias evolutionary trajectories and interactions between species. Lastly, these results and system provide a foundation to investigate evolutionary consequences in real time as newly acquired regions are ameliorated and integrated into new genomic contexts.     

Antiobesity and Antidiabetic β-agonists: Lessons Learned and Questions to be Answered

In several species of obese animals, a group of phenethanolamine β-agonists stimulates lipolysis and thermogenesis, resulting in the loss of body fat and weight. Brown adipose tissue is considered to be the major target tissue for the antiobesity activity of these compounds. Independent of this antiobesity activity, some of these compounds are also antidiabetic and increase muscle mass. Based on the pharmacological profile of these com-pounds, a npeceptor was proposed and character-ized in mouse, rat, and humans. The 133-receptor in brown adipose tissue has been suggested to mediate the antiobesity activity of these 13-agonists. Whether this receptor is responsible for the antidiabetic activ-ity and whether there is a linkage between the antiobesity/antidiabetic activity and the nutrient par-titioning activity is not clear. Clinical trials with these mixed 13-agonists showed marginal antiobesity effects when caloric intake of subjects was restricted. Insulin sensitivity was also improved in some of the trials designed to test the antidiabetic activity of these compounds. Side effects included tachycardia and tremor. To eliminate these side effects, a second generation of compounds was selected for its agonist activity on rat D3-receptors. Clinical trials with these compounds have shown lit-tle increase of energy expenditure even at high doses. Successful development of an antiohesity and antidi-abetic drug from this class of compounds will require the elucidation of the physiological role of the human 133-receptor and the regulatory mecha-nism between fuel efficiency and feeding behavior.     

Simulation of the effects of Acanthaster planci on the population structure of massive corals in the genus Porites: evidence of population resilience?

Scleractinian corals in the genus Porites are slow growing, can live for centuries, and can attain great size. In these respects they differ from the majority of coral species, which grow faster and live for years to decades. The predatory starfish Acanthaster planci L. feeds on a wide range of coral species including Porites spp., and during outbreaks in its populations, causes high coral mortality and injury over much of the affected reefs. Because they are slow growing and because recent outbreaks of the starfish occurred only 15 years apart, it may be argued that the Porites populations on affected reefs will be sent into a period of prolonged decline. The present study uses a size stage model of the transition matrix type to predict effects of starfish outbreaks of various frequencies on Porites populations. A transition matrix characterizing the mortality and injury caused in different Porites size classes at John Brewer Reef during an outbreak year was determined from field data. Transition matrices for non-outbreak years were constructed on the basis of realistic growth rates and postulated survivorship and recruitment schedules. The medium term (100 years) effects of outbreaks were simulated by alternation of a single iteration of the outbreak matrix with many iterations of each non-outbreak matrix. By varying the interval between simulated outbreaks it was possible to define combinations of growth rate, survivorship and recruitment which were viable for various outbreak intervals. Simulations based on estimates of the initial size frequency distribution, recruitment rates and colony growth rates for the John Brewer Reef population predicted that the population would remain viable in the face of outbreaks every 15 years only if juvenile and adult survivorship were high. However, within the range of colony growth rates known to occur throughout the Great Barrier Reef and at recruitment rates of the same order as those estimated in the field population, it appears that a much wider range of survivorship schedules could lead to parity or even sustained growth in the face of outbreaks recurring at intervals of from 1 to 3 decades. It is suggested that because the key measurable parameters (initial size structure, damage characteristics, recruitment rate and growth rate) are likely to be very patchy at the scale of whole reefs, no general statement concerning the prognosis for Porites would be meaningful. However the model provides a tool by which a standardized evaluation of this type of field data may be made on a reef by reef basis.