Variable clinical responses of a scrub typhus outbred mouse model to feeding by Orientia tsutsugamushi infected mites

Rodents are the natural hosts for Leptotrombidium mites that transmit Orientia tsutsugamushi, the causative agent of scrub typhus, a potentially fatal febrile human disease. Utilizing mite lines that included O. tsutsugamushi infected and non-infected Leptotrombidium species we investigated the varied infection response of outbred mice (ICR) exposed to L. chiangraiensis (Lc), L. imphalum (Li) and L. deliense (Ld). Each of six mite lines (Lc1, Lc5, Li3, Li4, Li7 and Ld) was separately placed in the inner ears of ICR mice either as a single individual (individual feeding, IF) or as a group of 2-4 individuals (pool feeding, PF). The species of infected chigger feeding on mice significantly affected mortality rates of the mice, with mite lines of Lc causing higher mean (±SE) mortality (90.7 ± 3.6 %) than mite lines of Li (62.9 ± 5.6 %) or Ld (53.6 ± 5.8 %). Mouse responses which included time to death, food consumption and total mice weight change depended on mite species and their O. tsutsugamushi genotype, more than on feeding procedure (IF vs. PF) except for mite lines within the Lc. Infected mite lines of Lc were the most virulent infected mites assessed whereas the infected Ld species was the least virulent for the ICR. Mice killed by various mite lines showed enlarged spleens and produced ascites. The results of this investigation of the clinical responses of ICR mice to feeding by various infected mite lines indicated that the different species of infected mites and their O. tsutsugamushi genotype produced different clinical presentations in ICR mice, a scrub typhus mouse model which mimics the natural transmission of O. tsutsugamushi that is critical for understanding scrub typhus disease in terms of natural transmission, host-pathogen-vector interaction and vaccine development.     

Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors

LAF389 is a synthetic analogue of bengamides, a class of marine natural products that produce inhibitory effects on tumor growth in vitro and in vivo. A proteomics-based approach has been used to identify signaling pathways affected by bengamides. LAF389 treatment of cells resulted in altered mobility of a subset of proteins on two-dimensional gel electrophoresis. Detailed analysis of one of the proteins, 14-3-3gamma, showed that bengamide treatment resulted in retention of the amino-terminal methionine, suggesting that bengamides directly or indirectly inhibited methionine aminopeptidases (MetAps). Both known MetAps are inhibited by LAF389. Short interfering RNA suppression of MetAp2 also altered amino-terminal processing of 14-3-3gamma. A high resolution structure of human MetAp2 co-crystallized with a bengamide shows that the compound binds in a manner that mimics peptide substrates. Additionally, the structure reveals that three key hydroxyl groups on the inhibitor coordinate the di-cobalt center in the enzyme active site.     

Laser-raman spectroscopic study of carbohydrates: 1-thio-β-d-hexopyranosides

Some β-d-hexopyranosides of 1-thio-d-glucose, 2-acetamido-2-deoxy-1-thio-d-glucose, and 1-thio-d-galactose were examined by laser-Raman spectroscopy. An anomeric CH bending vibration was found at 891 ± 7 cm^-1 for all compounds investigated; thus, the anomers of these sugars can be differentiated by Raman spectroscopy. The N-acetyl group and carboxyl group can also be detected by Raman spectroscopy. Unlike protein samples, the carbohydrates in aqueous solution yield less useful information from Raman spectra than in the solid state; this is due to the extensive overlapping of carbohydrate OH bands with water OH bands.     

CONVERGENT AND CORRELATED EVOLUTION OF MAJOR LIFE‐HISTORY TRAITS IN THE ANGIOSPERM GENUS LEUCADENDRON (PROTEACEAE)

Natural selection is expected to cause convergence of life histories among taxa as well as correlated evolution of different life‐history traits. Here, we quantify the extent of convergence of five key life‐history traits (adult fire survival, seed storage, degree of sexual dimorphism, pollination mode, and seed‐dispersal mode) and test hypotheses about their correlated evolution in the genus Leucadendron (Proteaceae) from the fire‐prone South African fynbos. We reconstructed a new molecular phylogeny of this highly diverse genus that involves more taxa and molecular markers than previously. This reconstruction identifies new clades that were not detected by previous molecular study and morphological classifications. Using this new phylogeny and robust methods that account for phylogenetic uncertainty, we show that the five life‐history traits studied were labile during the evolutionary history of the genus. This diversity allowed us to tackle major questions about the correlated evolution of life‐history strategies. We found that species with longer seed‐dispersal distances tended to evolve lower pollen‐dispersal distance, that insect‐pollinated species evolved decreased sexual dimorphism, and that species with a persistent soil seed‐bank evolved toward reduced fire‐survival ability of adults.     

Exploration Behavior and Morphology are Correlated in Captive Gray Mouse Lemurs (<Emphasis Type="Italic">Microcebus murinus</Emphasis>)

Behavior varies among individuals and is flexible within individuals. However, studies of behavioral syndromes and animal personality have demonstrated that animals can show consistency in their behavior and as such may be restricted in their behavioral responses. Like any other trait, including morphology, performance, or physiology, personality is now considered an important component of ecology and may have fitness consequences. Moreover, in some species personality correlates with other traits, as predicted in the context of a recent theoretical framework postulating that individual differences in growth and body size can affect behavior through effects on growth–mortality tradeoffs. This “pace of life” hypothesis predicts that animals that explore more should be larger and have higher growth rates than those that explore less. We tested for associations between morphology and a behavioral trait in a captive colony of gray mouse lemurs (Microcebus murinus). We used open-field tests to evaluate exploration behavior and measured a series of morphological traits in 72 individuals (32 males and 40 females). Our results show that the latency to start exploring correlates positively with adult body size and body weight at birth. These data provide evidence for a link between morphology and behavior in this species, thus supporting predictions of dispersal models but diverging from the predictions of the “pace of life” model.     

Mathematical model of fructan biosynthesis and polymer length distribution in plants

Background and Aims

There are many unresolved issues concerning the biochemistry of fructan biosynthesis. The aim of this paper is to address some of these by means of modelling mathematically the biochemical processes.

Methods

A model has been constructed for the step-by-step synthesis of fructan polymers. This is run until a steady state is achieved for which a polymer distribution is predicted. It is shown how qualitatively different distributions can be obtained.

Key Results

It is demonstrated how a set of experimental results on polymer distribution can by simulated by a simple parameter adjustments.

Conclusions

Mathematical modelling of fructan biosynthesis can provide a useful tool for helping elucidate the details of the biosynthetic processes.