The spatial and temporal dynamics of rabies in China

Background and Objectives

Recent years have seen a rapid increase in the number of rabies cases in China and an expansion in the geographic distribution of the virus. In spite of the seriousness of the outbreak and increasing number of fatalities, little is known about the phylogeography of the disease in China. In this study, we report an analysis of a set of Nucleocapsid sequences consisting of samples collected through the trial Chinese National Surveillance System as well as publicly available sequences. This sequence set represents the most comprehensive dataset from China to date, comprising 210 sequences (including 57 new samples) from 15 provinces and covering all epidemic regions. Using this dataset we investigated genetic diversity, patterns of distribution, and evolutionary history.

Results

Our analysis indicates that the rabies virus in China is primarily defined by two clades that exhibit distinct population subdivision and translocation patterns and that contributed to the epidemic in different ways. The younger clade originated around 1992 and has properties that closely match the observed spread of the recent epidemic. The older clade originated around 1960 and has a dispersion pattern that suggests it represents a strain associated with a previous outbreak that remained at low levels throughout the country and reemerged in the current epidemic.

Conclusions

Our findings provide new insight into factors associated with the recent epidemic and are relevant to determining an effective policy for controlling the virus.     

Biochemical and Functional Analysis of Two Plasmodium falciparum Blood-Stage 6-Cys Proteins: P12 and P41

The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here we investigate the biochemical nature and function of two blood-stage 6-cys proteins in Plasmodium falciparum, the most pathogenic species to afflict humans. We show that native P12 and P41 form a stable heterodimer on the infective merozoite surface and are secreted following invasion, but could find no evidence that this complex mediates erythrocyte-receptor binding. That P12 and P41 do not appear to have a major role as adhesins to erythrocyte receptors was supported by the observation that antisera to these proteins did not substantially inhibit erythrocyte invasion. To investigate other functional roles for these proteins their genes were successfully disrupted in P. falciparum, however P12 and P41 knockout parasites grew at normal rates in vitro and displayed no other obvious phenotypic changes. It now appears likely that these blood-stage 6-cys proteins operate as a pair and play redundant roles either in erythrocyte invasion or in host-immune interactions.     

alpha-Oligodeoxynucleotide stability in serum, subcellular extracts and culture media

Degradation of a synthetic alpha-oligodeoxynucleotide was studied in order to compare its survival with naturally occurring beta-oligodeoxynucleotides in five systems used for antisense hybridization arrest experiments. In contrast to beta-oligodeoxynucleotides, alpha-oligodeoxynucleotides were not detectably degraded over 24 h at 37 degrees C in HeLa cell postmitochondrial cytoplasmic extract or RPMI 1640 with 10% fetal bovine serum, and showed significant survival after 24 h at 37 degrees C in rabbit reticulocyte lysate, fetal bovine serum and human serum.     

The Pericyte of the Pancreatic Islet Regulates Capillary Diameter and Local Blood Flow

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The psychoactive substance of cannabis Δ9-tetrahydrocannabinol (THC) negatively regulates CFTR in airway cells

Background

Marijuana consumption is on the rise in the US but the health benefits of cannabis smoking are controversial and the impact of cannabis components on lung homeostasis is not well-understood. Lung function requires a fine regulation of the ion channel CFTR, which is responsible for fluid homeostasis and mucocilliary clearance. The goal of this study was to assess the effect that exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive substance present in marijuana, has on CFTR expression and function.

NMR study of a heterochiral DNA hairpin:impact of L-enantiomery in the loop.

We carried out a structural study of the DNA heterochiral strand d (AGCTTATCAT(L)CGATAAGCT), -AT(L)C-, where T(L) (L thymine ) replaces T (natural D-thymine). -AT(L)C- is a structural analog of -ATC- that belongs to a strong topoisomerase II DNA cleavage site and which has been shown to resolve into a hairpin structure with a stem formed by eight Waston-Crick base-pairs and a single residue loop closed by an A.C sheared base-pair. Although - AT(L)C-, like its parent -ATC-, folds into a hairpin structure at low and high DNA concentrations it displays a lower stability (Tm of 56 degrees C versus 58.5 degrees C). Several NMR features in -AT(L)C- account for the disruption of the A.C pairing in the loop and a weakening of the C.G base-pair stability at the stem-loop junction. For instance, the exchange of the loop imino protons with solvent is accelerated compared with the natural oligonucleotide -ATC-. The higher flexibility of the heterochiral loop is confirmed by the results of NMR restrained molecular dynamics. In the calculated final structures of -AT(L)C-, the T10(L) residue moves the A9 and C11 residues away, thus preventing the loop closure through a C.A sheared base-pair and the achievement of a good base-base or sugar-base stacking. Actually, most of the stabilizing interactions present in -ATC- are lost in the heterochiral - AT(L)C- explaining its weaker stability.     

Avian brachial index and wing kinematics: putting movement back into bones

The relationship between wing kinematics, wing morphology and the brachial index of birds (BI=humerus length/ulna length) was examined. BI was found to differ between three groups of birds, which were classified on the basis of similar wing kinematics. In addition, a comparative analysis of a large dataset, using phylogenetically independent contrasts, suggested a significant, albeit weak, correlation between BI and four measures of wing morphology (wing loading, wing area, wing length and aspect ratio). Although wing kinematics and wing morphology are both correlated with BI in birds, the dominant selective pressure upon this ratio is probably wing kinematics. The previously identified clade specificity of BI within Neornithes is most likely because birds with similar BIs fly with kinematic similarity and closely related birds have similar flight styles. A correlation between BI and wing kinematics means that it may be possible to characterize the wing beat of fossil birds. A more robust relationship between wing morphology and BI may emerge, but only after the relationship between wing kinematics and BI is quantified. A comparative and quantitative study of wing-bone anatomy and wing kinematics is a priority for future studies of avian wing-skeleton evolution and functional morphology.